[Senate Hearing 107-326]
[From the U.S. Government Publishing Office]



                                                        S. Hrg. 107-326
 
  MAKING SENSE OF THE MAMMOGRAPHY CONTROVERSY: WHAT WOMEN NEED TO KNOW
=======================================================================



                             JOINT HEARING

                               BEFORE THE

                     SUBCOMMITTEE ON PUBLIC HEALTH

                                 OF THE

                    COMMITTEE ON HEALTH, EDUCATION,
                          LABOR, AND PENSIONS
                          UNITED STATES SENATE

                                AND THE

    SUBCOMMITTEE ON LABOR, HEALTH, AND HUMAN SERVICES, AND EDUCATION

                                 OF THE

                      COMMITTEE ON APPROPRIATIONS
                          UNITED STATES SENATE

                      ONE HUNDRED SEVENTH CONGRESS

                             SECOND SESSION

                                   ON

  EXAMINING THE CONFLICTING FINDINGS REGARDING MAMMOGRAPHY USAGE AND 
UPDATE RECOMMENDATION GUIDELINES, BASED ON THE MOST CURRENT SCIENTIFIC 
       DATA, ON THE USE OF MAMMOGRAPHY IN BREAST CANCER DETECTION

                               __________

                           February 28, 2002

                               __________

 Printed for the use of the Committee on Health, Education, Labor, and 
                                Pensions







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          COMMITTEE ON HEALTH, EDUCATION, LABOR, AND PENSIONS

               EDWARD M. KENNEDY, Massachusetts, Chairman
CHRISTOPHER J. DODD, Connecticut     JUDD GREGG, New Hampshire
TOM HARKIN, Iowa                     BILL FRIST, Tennessee
BARBARA A. MIKULSKI, Maryland        MICHAEL B. ENZI, Wyoming
JAMES M. JEFFORDS (I), Vermont       TIM HUTCHINSON, Arkansas
JEFF BINGAMAN, New Mexico            JOHN W. WARNER, Virginia
PAUL D. WELLSTONE, Minnesota         CHRISTOPHER S. BOND, Missouri
PATTY MURRAY, Washington             PAT ROBERTS, Kansas
JACK REED, Rhode Island              SUSAN M. COLLINS, Maine
JOHN EDWARDS, North Carolina         JEFF SESSIONS, Alabama
HILLARY RODHAM CLINTON, New York     MIKE DeWINE, Ohio
           J. Michael Myers, Staff Director and Chief Counsel
             Townsend Lange McNitt, Minority Staff Director
                                 ------                                

                     Subcommittee on Public Health

                      EDWARD M. KENNEDY, Chairman
TOM HARKIN, Iowa                     BILL FRIST, Tennessee
BARBARA A. MIKULSKI, Maryland        JUDD GREGG, New Hampshire
JAMES M. JEFFORDS, Vermont           MICHAEL B. ENZI, Wyoming
JEFF BINGAMAN, New Mexico            TIM HUTCHINSON, Arkansas
PAUL D. WELLSTONE, Minnesota         PAT ROBERTS, Kansas
JACK REED, Rhode Island              SUSAN M. COLLINS, Maine
JOHN EDWARDS, North Carolina         JEFF SESSIONS, Alabama
HILLARY RODHAM CLINTON, New York     CHRISTOPHER S. BOND, Missouri
                      David Nexon, Staff Director
                 Dean A. Rosen, Minority Staff Director
                                 ------                                

                                  (ii)












                      COMMITTEE ON APPROPRIATIONS

                ROBERT C. BYRD, West Virginia, Chairman
DANIEL K. INOUYE, Hawaii             TED STEVENS, Alaska
ERNEST F. HOLLINGS, South Carolina   THAD COCHRAN, Mississippi
PATRICK J. LEAHY, Vermont            ARLEN SPECTER, Pennsylvania
TOM HARKIN, Iowa                     PETE V. DOMENICI, New Mexico
BARBARA A. MIKULSKI, Maryland        CHRISTOPHER S. BOND, Missouri
HARRY REID, Nevada                   MITCH McCONNELL, Kentucky
HERB KOHL, Wisconsin                 CONRAD BURNS, Montana
PATTY MURRAY, Washington             RICHARD C. SHELBY, Alabama
BYRON L. DORGAN, North Dakota        JUDD GREGG, New Hampshire
DIANNE FEINSTEIN, California         ROBERT F. BENNETT, Utah
RICHARD J. DURBIN, Illinois          BEN NIGHTHORSE CAMPBELL, Colorado
TIM JOHNSON, South Dakota            LARRY CRAIG, Idaho
MARY L. LANDRIEU, Louisiana          KAY BAILEY HUTCHISON, Texas
JACK REED, Rhode Island              MIKE DeWINE, Ohio
                  Terrence E. Sauvain, Staff Director
                 Charles Kieffer, Deputy Staff Director
               Steven J. Cortese, Minority Staff Director
            Lisa Sutherland, Minority Deputy Staff Director
                                 ------                                

 Subcommittee on Departments of Labor, Health and Human Services, and 
                    Education, and Related Agencies

                       TOM HARKIN, Iowa, Chairman
ERNEST F. HOLLINGS, South Carolina   ARLEN SPECTER, Pennsylvania
DANIEL K. INOUYE, Hawaii             THAD COCHRAN, Mississippi
HARRY REID, Nevada                   JUDD GREGG, New Hampshire
HERB KOHL, Wisconsin                 LARRY CRAIG, Idaho
PATTY MURRAY, Washington             KAY BAILEY HUTCHISON, Texas
MARY L. LANDRIEU, Louisiana          TED STEVENS, Alaska
ROBERT C. BYRD, West Virginia        MIKE DeWINE, Ohio
                           Professional Staff
                              Ellen Murray
                              Jim Sourwine
                              Mark Laisch
                            Adrienne Hallett
                              Erik Fatemi
                       Bettilou Taylor (Minority)
                        Mary Dietrich (Minority)
                    Sudip Shrikant Parikh (Minority)
                       Candice Rogers (Minority)

                         Administrative Support
                             Carole Geagley
















                            C O N T E N T S

                              ----------                              

                               STATEMENTS

                           February 28, 2002

                                                                   Page
Mikulski, Hon. Barbara A., a U.S. Senator from the State of 
  Maryland, opening statement....................................     1
Specter, Hon. Arlen, a U.S. Senator from the State of 
  Pennsylvania, opening statement................................     2
Harkin, Hon. Tom, a U.S. Senator from the State of Iowa, opening 
  statement......................................................     8
Reed, Hon. Jack, a U.S. Senator from the State of Rhode Island, 
  opening statement..............................................    10
Von Eschenbach, Andrew, M.D., Director, National Cancer 
  Institute, National Institutes of Health, U.S. Department of 
  Health and Human Services, prepared statement..................    14
Berry, Donald A., M.D., Chairman, Department of Biostatistics, 
  Anderson Cancer Center, Unibersity of Texas, Houston, TX; and 
  Harmon J. Eyre, M.D., Chief, Medical Officwer and Executive 
  Vice President ofr Research and Medical Affairs, American 
  Cancer Society, Washington, DC.................................    44
    Prepared Statements of:
        Donald A. Berry, M.D.....................................    46
        Harmon J. Eyre, M.D......................................    52
Visco, Fran, President, National Breast Cancer Coalition, 
  Washington, DC; Carolyn D. Runowicz, M.D., Vice Chariman, 
  Department of Obsttretrics and Gynecology, Saint Luke's 
  Roosevelt Hospital, New York, NY, On Behalf of the American 
  College of Obstretricians, and Gynecologists; and LaSalle 
  Leffall, Jr., M.D., Chairman-Elect, Susan G. Komen Breast 
  Cancer Foundation, Dallas, TX..................................    65
    Prepared Statements of:
        Fran Visco...............................................    67
        Carolyn D. Runowicz, M.D.................................    73
        LaSalle D. Leffall, Jr., M.D.............................    76

                          ADDITIONAL MATERIAL

Articles, publications, letters, etc.:
    Danish Study.................................................    21
    Claudia I. Henschke, PhD., M.D...............................    88
    Letter to Senator Specter from UPMC Health System............    89
    Agency for Healthcare Research and Quality...................    89
    Food and Drug Administration, Department of Health and Human 
      Services...................................................    92
    Letter to Senators Kennedy and Gregg from the Oncology 
      Nursing Society............................................    94
    Samuel B. Wallace............................................    96

                                  (V)













  MAKING SENSE OF THE MAMMOGRAPHY CONTROVERSY: WHAT WOMEN NEED TO KNOW

                              ----------                              


                      THURSDAY, FEBRUARY 28, 2002

                                               U.S. Senate,
       Subcommittee on Public Health, Committee on Health, 
Education, Labor, and Pensions, and Subcommittee on Labor, 
    Health and Human Services, and Education, Committee on 
                                            Appropriations,
                                                    Washington, DC.
    The joint hearing convened at 2:28 p.m., in room SD-106, 
Dirksen Senate Office Building, Hon. Barbara Mikulski, 
presiding.
    Present: Senators Mikulski, Harkin, Murray, Reed, Clinton, 
Specter, and Frist.

                 Opening Statement of Senator Mikulski

    Senator Mikulski. [presiding]. Good afternoon.
    This is a joint hearing between the Subcommittee on Public 
Health of the Health, Education, Labor, and Pensions Committee 
as well as the Appropriations Subcommittee on Labor, Health and 
Human Services, and Education.
    We are holding a joint hearing because of the advocacy of 
the members and the way that both the authorizing and 
appropriating committees have worked together.
    The title of this hearing is ``Making Sense of the 
Mammogram Controversy: What Women Need to Know.''
    As chair of the hearing, I wish to yield to the ranking 
member of the Appropriations Committee, Senator Arlen Specter. 
Senator Specter is co-chair of the Steel Caucus, and he, along 
with other Steel Caucus members, has a meeting with the 
President in about 20 minutes.
    As a Senatorial courtesy, we would like him to go first, 
because he is going to go and be representing thousands of 
steel workers, and as a member of the Steel Caucus, Senator, my 
thoughts go with you. I will hold the fort here at the 
committee, and I know you will with the President.
    I would ask my colleague to proceed, and I just want to 
emphasize what a bipartisan effort this is, helping women to be 
protected from the ravages of breast cancer, and what a strong 
advocate Senator Specter has been for the empowerment of women 
in being able to have the health care they need.
    Senator?

                  Opening Statement of Senator Specter

    Senator Specter. Thank you very much, Madam Chairperson, 
for your initiatives and your leadership in convening this 
important hearing, and thank you for yielding to me for a few 
moments.
    Senator Mikulski and I have just come from the Ellipse. It 
is about 35 degrees outside in Washington today, and there was 
a rally of some 25,000 steel workers who came to urge the 
President to impose tariffs to allow the steel industry to 
revitalize itself. Senator Mikulski and I spoke there, and we 
are glad to be indoors for a few minutes at this time.
    As Senator Mikulski has said, the President has scheduled a 
meeting of the Steel Caucus of which I am vice chairman, and we 
will be meeting with the President shortly to make the case as 
to why we ought to stop subsidized and dumped steel from coming 
into the United States, costing the bankruptcies of many 
corporations, the loss of hundreds of thousands of jobs and 
impairing our capacity for national defense.
    But I wanted to be here for at least a few minutes this 
morning, and I will return if I can before the hearing is 
concluded, on this very important subject of mammography.
    I chaired the appropriations subcommittee which funded the 
Department of Health and Human Services in 1997, when a 
controversy arose as to whether there should be mammograms for 
women between the ages of 40 and 49 and, in my capacity as 
chairman of that subcommittee, initiated a series of hearings 
on the subject and became personally convinced that the 
mammograms could be helpful--not necessarily but possibly so, 
that if a noninvasive screening process could detect breast 
cancer at an early age and save lives, and the statistics are 
just devastating as to how many women die of breast cancer each 
year, it ought to be available.
    The issue came before the appropriations subcommittee 
because it was a matter of cost. Senators ought not decide 
medical questions; we ought to leave that to the experts. But 
when it comes to the issue of establishing priorities on where 
expenditures ought to be allocated, that is the prerogative of 
the Members of Congress of the House and Senate.
    We decided that we could afford it, and that is part of 
what Senator Harkin and I have done on many of these important 
medical issues. Senator Harkin and I have taken the lead on 
funding for NIH from $12 billion a year to $23 billion a year. 
We are a rich and powerful country, and we can afford that. And 
the funding for cancer has increased enormously, including 
funding for breast cancer. Of the $2.1 trillion which is spent 
by the United States Government each year, none is spent for a 
better purpose than to try to eradicate breast cancer, prostate 
cancer, eliminate Alzheimer's, Parkinson's, and heart disease. 
There is nothing more important than health.
    So I am pleased that these hearings have been convened. Let 
us take a fresh look at the matter. There is some potential if 
someone has a mammogram and there is a false positive, but my 
own personal view after studying the matter in great detail is 
that that is of lesser consequence than the availability of 
screening to detect cancer at an early stage where it can be 
successfully treated. And I believe that the United States 
Government has the funding to make such mammography available 
for women ages 40 to 49; but reconsideration is always fine.
    Since I have to leave, I want to introduce Ms. Fran Visco, 
who is president of the National Breast Cancer Coalition and a 
member of the board of directors. President Clinton appointed 
her as a member of the President's Cancer Panel. She has a 
degree from Saint Joe's and a law degree from Villanova Law 
School, and she is a Pennsylvanian, which gives us special 
pride.
    While I am at it, I want to note the presence of the 
distinguished new head of the National Cancer Institute, Dr. 
von Eschenbach, who comes from South Philadelphia. It is a high 
honor to be director of the National Cancer Institute, and it 
may be an even higher honor to be from South Philadelphia.
    Thank you very much, Senator Mikulski.
    Senator Mikulski. Thank you, Senator, and good luck to you 
in your meeting with the President. Give him my regards that it 
is a bipartisan effort. We have got to be Team USA here.
    Thank you.
    In my own opening statement, I want to say that the title 
of this hearing is ``Making Sense of the Mammogram Controversy: 
What Women Need to Know,'' and what women need to do.
    Today we are here to examine the very troubling controversy 
about the effectiveness of screening mammography. Women are 
hearing conflicting scientific studies. Some studies say that 
mammogram save lives. Others say they do not. This is 
incredibly frustrating for American women. Many are confused, 
exasperated, and apprehensive, both about breast cancer and now 
about the information they are getting about mammography. They 
do not know what to do, whom to believe, or where to go.
    I am very concerned myself. I called this hearing to get 
answers for American women. What should they do? Where can they 
get information they can rely upon?
    Also, in the absence of conclusive information, I am 
worried that insurance companies will wiggle out of providing 
this coverage, saying that it is no longer a mandate for 
prevention but a personal option. I do not believe that 
mammograms should be equated with nose jobs. I do believe that 
mammograms save lives, and we need to know when is the best 
time to get them.
    There are conflicting studies. Recent work by 
biostatisticians in Denmark concluded that there is no reliable 
evidence that regular mammograms save lives. Here in the United 
States, the Physicians' Data Query Screening and Prevention 
Board--which, by the way, is an independent group of experts 
created and funded by the National Cancer Institute--has come 
up with these observations. They have signalled yellow flashing 
lights about whether mammograms provide any benefit to women. 
These findings conflict with other studies showing that 
screening mammograms can reduce breast cancer deaths by 30 
percent.
    Then, in the atmosphere of these conflicting studies, last 
week, Secretary Tommy Thompson affirmed the Department's 
traditional position that regular mammograms do benefit women 
and cited the Preventive Services Task Force. But at that time, 
Secretary Thompson, a longstanding advocate of women's health, 
did not give us data.
    Many other organizations like the American Cancer Society 
also continue to recommend screening mammograms.
    So today, we want to hold a hearing. This is not a debate. 
It is a presentation of views in which we hope we can clear the 
air and clear up what women should do. I understand dissent in 
the scientific community and difference of opinion about 
particular studies, but this conflict is exasperating. Women do 
not know whom to believe or what they should do.
    My own position is that I would rather be safe than sorry. 
But I also have the means to pay for a mammogram. What about 
women who do not have the ability to pay? What happens if 
insurance companies decide to stop paying? And in the absence 
of clarity, I am concerned that conflicting studies will give 
women pause rather than pursuing prevention.
    We do need new tools and techniques regardless of the 
efficacy of mammograms. Right now, what we do know is that the 
mammogram is the best tool we now have--but it should not be 
the only tool. Hopefully, there will be more in the future. We 
need new tools and accurate testing to make sure they work. We 
cannot afford to have the same controversy over and over again.
    The Institute of Medicine has recommended improving the 
development and adoption of new technologies as well as 
maximizing the technology currently available for breast cancer 
detection. These recommendations should be seriously 
considered.
    At the same time that we look at new technologies, we have 
to make sure that mammograms, regardless of when we are advised 
to get them, are safe. That is why in 1992, I led the way to 
ensuring that we had Mammogram Quality Safety Standards to be 
sure that they are safe and accurate, to avoid, of course, the 
terrible situation of false negatives. These Mammogram Quality 
Standards are now up for reauthorization, and we hope to be 
able to expedite that and look forward to any comments that 
others wish to make.
    This hearing brings together the Public Health Subcommittee 
and the Labor-HHS Appropriations Subcommittee to look at these 
issues. I am happy to say that I am joined by Senator Tom 
Harkin, who chairs the Labor-HHS Appropriations Subcommittee. 
Senator Harkin is a longstanding advocate for doubling the 
funding for the NIH budget, to ensuring that American people 
have access to health care and the cures that they help pay to 
discover, and at the same time, when women were not even 
included in the clinical trials, he was a real Galahad to make 
sure we created the Office of Women's Health at NIH and had the 
money in the Federal checkbook so that we could pursue those 
issues of research in breast and ovarian cancer.
    So, Senator Harkin, we thank you for being here, and of 
course, we welcome Dr. Andrew von Eschenbach.
    [The prepared statement of Senator Mikulski follows:]

                 Prepared Statement of Senator Mikulski

    Today we are here to examine a troubling controversy about 
the effectiveness of screening mammography. Women are hearing 
about conflicting scientific studies. Some say mammograms save 
lives. Others say they don't. This is incredibly frustrating 
for women. Many are already apprehensive about breast cancer. 
Now they don't know what to do or who to believe.
    I am frustrated myself. I called this hearing to get some 
answers for American women. What should they do? Where do they 
get information they can trust? We also don't want insurance 
companies to wiggle out of providing this coverage because they 
say the data is inconclusive.
    Recent work by statisticians Dr. Peter Gotzsche and Ole 
Olsen of the Nordic Cochrane Center in Denmark concluded that 
there is no reliable evidence that regular mammograms save 
lives. This finding conflicts with other studies showing that 
mammograms reduce breast cancer deaths by about 30%. Here in 
the United States, the Physicians' Data Query Screening and 
Prevention Board, a panel of independent experts created and 
funded by the National Cancer Institute, has signaled its 
yellow flashing lights about whether mammograms provide any 
benefit to women. Last week, Secretary Tommy Thompson 
reaffirmed the Department's position that regular mammograms do 
benefit women. Many other organizations, like the American 
Cancer Society, also continue to recommend screening 
mammograms.
    I understand dissent in the scientific community and 
differences of opinion about particular studies, but this 
conflict is exasperating. Women don't know who to believe or 
what they should do--do they get a mammogram or not? My 
position is that I would rather be safe than sorry, but I have 
the means to pay for a mammogram. What about women who don't 
have the ability to pay and whose insurance companies may 
decide to stop paying for mammograms? In the absence of 
clarity, I'm concerned that these conflicting studies give an 
excuse to insurance companies to stop paying for mammograms.
    I'm not mandating an outcome, but this is very troubling. I 
speak for the women of the Senate and I salute the wonderful 
men who are so supportive and real champions like Senators 
Harkin, Specter, and Frist.
    Mammography is the best tool we have now, but it is not the 
only one and there will be more in the future. We need new 
tools and accurate testing to make sure they work. We cannot 
afford to have this same controversy over and over. A report 
last year by the Institute of Medicine recommended improving 
the development and adoption of new technologies, as well as 
maximizing the technologies currently available for breast 
cancer detection. These recommendations should be seriously 
considered.
    Mammography is not perfect, but it is the best screening 
tool we have now. Mammograms must be as safe and accurate as 
possible. A mammogram is worse than useless if it produces a 
poor-quality image or is misinterpreted. That's why I have 
fought over the last ten years to make them even better. The 
Mammography Quality Standards Act (MQSA) that I authored has 
improved the quality of mammograms in this country over the 
last ten years. MQSA has brought facilities nationwide into 
compliance with federal quality standards. Before MQSA, tests 
were misread, women were misdiagnosed, and people died as a 
result of sloppy work. This year Congress must reauthorize the 
Mammography Quality Standards Act, because women must continue 
to have safe, quality mammograms. Until there are more 
effective screening tools, mammography is still the front line 
against breast cancer.
    This hearing brings together the Public Health Subcommittee 
and the Labor/HHS Appropriations Subcommittee to look at this 
issue of great importance to women. I look forward to the 
testimony of our witnesses and the expertise they bring. I 
extend a warm welcome to Dr. Andrew von Eschenbach, the new 
Director of the National Cancer Institute, as he testifies at 
his first hearing. I also enter into the record statements from 
the Food and Drug Administration and the Agency for Healthcare 
Research and Quality that are valuable contributions to this 
hearing. Whether or not to get a mammogram is a decision faced 
by millions of women. They are looking for answers and 
recommendations based on sound science, and they deserve no 
less.
    Senator Mikulski. Before I turn to Senator Harkin, I would 
like to note that Senator Olympia Snowe, a dear colleague, will 
not be able to attend today. For more than 20 years in the 
House and the Senate, we have been paired up as advocates in 
terms of helping not only to race for the cure but to race for 
every other tool we had to be able to find a cure and for 
prevention.
    Senator Snowe has sent a statement for the record, and I 
ask unanimous consent that it be included in the record.
    [The prepared statement of Senator Snowe follows:]

                  Prepared Statement of Senator Snowe

    Chairwoman Mikulski, Chairman Harkin, thank you for 
inviting me to join you and your committees today for this very 
important hearing, as we try to make sense of the controversy 
surrounding the merits of mammograms. Having worked with both 
of you over many years on this issue, I am pleased to have this 
opportunity to continue our joint efforts to improve women's 
health.
    The uncertainty around the merits of mammography has gone 
on for almost 25 years, beginning in 1977 when the National 
Cancer Institute stopped recommending mammograms for women in 
their 40s. Since then, there have been three additional 
reversals of the policy on mammography for this class of women 
. . .
    And what has all of this back and forth accomplished? Well 
it's done only one thing well, and that's create confusion and 
uncertainty on a matter that's central to a woman's health. As 
this debate wears on, women are becoming more and more 
uncertain of what science and what good health practices 
dictate they should do to be a partner in the fight against 
cancer, using the best weapon we all know of . . . early 
detection. Putting aside for a moment the controversy 
surrounding mammograms, no one can argue that early detection 
is not a critical component in the fight against breast cancer. 
Finding breast cancer earlier through mammography and earlier 
treatment has led to a steady decline in death rates. Not 
coincidently, as the number of women who received mammograms 
doubled, the average size of a tumor when it is originally 
detected has shrunk from three centimeters to two. And both 
common sense and experience tells us that detecting the tumor 
earlier, when it's smaller, improves the ability to treat the 
cancer before it spreads.
    Women have certainly taken the importance of routine 
mammograms and early detection to heart, playing an active role 
in their health maintenance by getting their annual or bi-
annual screening. In fact, according to the 2000 Behavioral 
Risk Factor Surveillance System, the percentage of U.S. women 
aged 40 and older who had a recent mammogram was almost 63 
percent.
    And why are women consistently going for these screenings? 
Consider the everyday experience of women, knowing not only the 
grim statistics that one in eight women will develop breast 
cancer in their lifetime, but also--all too often--having 
personal experience in confronting the devastation of breast 
cancer, when facing the diagnosis of a grandmother, mother, 
sister, or friend. I know the impact my mother's diagnosis had 
on me, as an eight-year old, and the impact her death from the 
disease had on inspiring me to make combating breast cancer a 
top priority.
    And yet, the debate about the efficacy of mammograms has 
thrown a shadow over the one tool available to women to protect 
themselves. The latest round in this debate began last fall, 
when the British medical journal, The Lancet published a Danish 
study which re-examined and confirmed the authors' original 
opinion that ``there is no reliable scientific evidence that 
screening for breast cancer reduced mortality.'' Having been 
active in this debate throughout my tenure in Congress and as 
the author, with Senator Mikulski, of the 1997 resolution 
adopted unanimously by the Senate highlighting the need for 
accurate guidelines for mammography for women in their 40s, I 
am concerned, but not surprised, that this controversy has 
arisen again.
    My concern led me, along with Senator Mikulski, to write to 
the Acting Director of the National Cancer Institute requesting 
that NCI, among other things, clarify the conflicting findings 
and recommend updated guidelines for the use of mammography in 
breast cancer detection. We have also been in contact with the 
newly-appointed Director, Dr. von Eschenbach, who is appearing 
today. Dr. von Eschenbach has been very receptive to our 
concerns and has indicated his intent to be active on this 
issue.
    We did not need to wait too long for this action, as last 
week, NO endorsed the recommendation of Health and Human 
Services Secretary Thompson, affirming the current 
recommendation that women in their forties get a mammogram once 
every year or two. These strong endorsements of routine 
mammograms were a definitive signal as to the position of the 
public health infrastructure. While their statements are 
encouraging, as long as the controversy remains in the national 
press, it will continue to weigh heavily on women and their 
families, on a matter that is too often of life and death.
    It is my sincere hope that this hearing will be the 
beginning of the end of the almost twenty-five year controversy 
surrounding the value of mammography. Certainly, we all 
recognize that there is no ``silver bullet'' in the fight 
against breast cancer--or any cancer for that matter. But, in 
order to fight this fight the best we can, it's critical that 
we use all the tools in our arsenal. Today, early detection of 
cancer through mammograms represents a powerful weapon in the 
war against cancer and I hope and trust that through 
investments in research we will continue to develop new and 
better weapons to fight cancer. But until that day comes, I 
urge the witnesses here today to continue their efforts to make 
this a reality. Thank you.
    Senator Mikulski. Senator Harkin, I will now turn to you.

                  Opening Statement of Senator Harkin

    Senator Harkin. Senator Mikulski, thank you very much, 
first for your dynamic and great leadership on so many issues 
that affect the health and welfare of the people of our 
country, but especially on this issue. You are more than 
generous in your remarks about my work in this area, but I can 
assure you that I am just following your lead.
    Senator Mikulski correctly stated that in 1992 she authored 
the legislation that provided for standardization and quality 
in terms of mammograms and the interpretation of mammograms. So 
I know that what is transpiring right now is of the utmost 
importance to her, as it is to all of us. But she really took 
the lead on this, and I just want to thank her for her 
foresight 10 years ago in addressing this issue.
    I also want to thank you, Senator Mikulski, for your work 
on our committee to make sure that we get the funds needed for 
intervention and especially for research. We made a commitment 
5 years ago as a Congress, the Senate and the House, that we 
were going to double funding for NIH over 5 years and with the 
budget this year we will accomplish that goal. Of course, a 
great deal of that goes into research on cancer and also into 
breast cancer research.
    I think that what we have to keep in mind is that we have 
an epidemic in this country of breast cancer. This is an 
epidemic by any yardstick or measurement. One out of every nine 
women in America will get breast cancer in their lifetime. 
Every 3 minutes, a woman is diagnosed with breast cancer in 
this country. Every 13 minutes, a woman dies of breast cancer 
in this country. That is an epidemic.
    I know these are statistics and we frequently throw out 
figures and statistics. But these statistics involve real 
people. One reason I have been so involved in this is--and I am 
frank to admit it--personal. My only two sisters died of breast 
cancer at quite an early age. They had young families. Had they 
had early intervention and early screening, I daresay they 
would have lived a lot longer and would be alive today.
    Now I have nieces, my sister's daughters, who, because both 
of their mothers died of breast cancer, I some time ago 
advised--I should not say I advised them because I am not a 
doctor--but I counseled them about getting early mammogram 
screenings because of perhaps some genetic susceptibility or 
something like that. So they started to have mammograms at an 
early age. One of them called me the other day and said, 
``Uncle Tom, what am I supposed to do now?'' I said, ``I don't 
know, but we will get the answers.''
    Just yesterday I had a conference call with a number of 
doctors and nurses and breast cancer survivors in my State of 
Iowa. I think the consensus was clear, Senator Mikulski, as you 
stated in your statement, that there is no confusion and no 
dissension among any of them. They believe mammograms are a 
very useful tool. They are not the cure-all; they are not the 
only thing to do. But combined with self-examination and annual 
physicals, mammograms can be the key to early detection. And we 
all know that early detection and early intervention means a 
woman can live longer and have a better quality of life.
    So I hope we can clear up some of this. I am sorry I came 
in a little late, Madam Chair. I just heard you say that we are 
not here to debate or anything like that. I understand that, 
but I think we are here to shed some light on these studies. We 
are here to find out from the experts and from breast cancer 
survivors, people who have been involved in this for a long 
time--I see Fran Visco out there--who can give us some guidance 
and direction and who can reassure the women of this country of 
what they should do to protect their health and make sure they 
get early screening and early intervention.
    So Madam Chair, let me again thank you for taking the lead 
in this. Thank you for pulling our two committees together to 
look at this and to have what I think is a very, very vital 
hearing at this point in time.
    Thank you, Madam Chair.
    [The prepared statement of Senator Harkin follows:]

                  Prepared Statement of Senator Harkin

    Thank you, Senator Mikulski and thank you for joining me in 
chairing this joint hearing on the benefits of mammography. I 
am pleased that we have such a distinguished panel of witnesses 
with us this afternoon. I particularly want to welcome the new 
director of NCI, Dr. Andrew von Eschenbach, who is making his 
first appearance before our subcommittee.
    Breast cancer is a disease I take very seriously. I lost my 
only two sisters to this killer. Sadly, they contracted the 
disease at a time when regular mammograms and improved 
treatment methods were not widely used or available. I'm 
convinced to this day had they gotten regular screenings, they 
would have lived longer lives.
    We have a breast cancer epidemic in this country. Every 
three minutes, a woman is diagnosed with breast cancer, and 
every 13 minutes, a woman dies from the disease. We need to 
wage a war against this epidemic. And as with any war, you want 
all the tools in your arsenal to maximize your chance of 
victory. And so while there have been conflicting studies, I 
believe we need to keep screening mammography in our arsenal. 
In fact, for women age 50 to 69, there is strong evidence that 
screening with mammograms on a regular basis reduces breast 
cancer deaths by 25 percent to 30 percent.
    I have read quite a bit about the new study by a pair of 
Danish researchers. I have also heard that this has led to a 
lot of confusion by woman facing the decision of whether to be 
screened regularly.
    Yesterday, I talked by phone to a number of clinicians and 
breast cancer survivors in Iowa. There was no confusion with 
them. These Iowans, who work with patients every day feel very 
strongly about the benefits of mammography and the early 
detection that it provides. Every one of them had a personal 
story about an Iowan, whose cancer was detected early by a 
mammogram, and is now doing very well. They all agreed that 
access to mammography is critical. Especially for Medicare 
beneficiaries.
    So I believe we need to redouble our efforts to maintain 
women's access to screening. That means improving Medicare's 
unacceptably low reimbursement rates and continuing to expand 
the breast and cervical cancer screening program.
    But, let me be clear, mammography is not a cure all. We 
need to continue our efforts to improve treatments and 
eventually develop a vaccine or cure for breast cancer. That is 
the ultimate victory. And the key is research. A decade ago, 
the Federal Government spent barely $90 million on breast 
cancer research. Today, I am proud to say, we've increased that 
investment to about $800 million. That investment is leading to 
new discoveries about the causes of breast cancer and its 
prevention, detection, diagnosis, treatment and control.
    Given the stakes, I'm very interested to hear from the 
experts we have here today. With that, I'll turn to my 
colleague, Senator Specter, for his opening statement.
    Senator Mikulski. Thank you, Senator Harkin.
    Senator Reed?

                   Opening Statement of Senator Reed

    Senator Reed. Thank you very much, Madam Chairman.
    I simply want to commend you for taking the initiative 
along with Senator Harkin on this very important issue and 
simply add to your praise of both Senator Harkin and Senator 
Specter for their role over many years in trying to ensure that 
we have the resources to provide support in this very important 
area.
    But ultimately, your leadership, Madam Chairwoman, has been 
the critical factor, I think, in this whole debate. I am here 
to learn and to listen, and with that, I will yield back my 
time.
    Senator Mikulski. Thank you.
    At this time I submit for the record statements from 
Senator Jeffords and Senator Hutchison.
    [The prepared statement of Senators Jeffords and Hutchison 
follow:]

                 Prepared Statement of Senator Jeffords

    Madam Chairwoman, I want to commend you for holding this 
timely hearing on the quality of mammography screening. I also 
would like to extend a warm welcome to the panel of expert 
witnesses here today. I look forward to your testimonies so 
that we may all gain a better understanding of the current 
controversy surrounding mammography. It is my hope that this 
and other sessions like it will lead us all to better, more 
informed solutions in the fight against cancer. We have made 
remarkable progress in the areas of research, diagnosis and 
treatment over the 30 years since we first declared the ``war 
on cancer'', but much more remains to be done. In my own home 
state of Vermont, the American Cancer Society estimates nearly 
3,000 new cancer cases, including hundreds of new breast cancer 
cases in the year 2002 alone.
    Recent studies have raised questions and left doubts for 
millions of women and their loved ones about the efficacy of 
mammography screening. Given these new uncertainties, I think 
it is all the more important that the public gets the best 
information and analysis available. We must continue to make 
accurate information available, and we need to avoid confusing 
the women for whom this issue is so vitally important. I hope, 
as we all do, that we will soon arrive at answers to the many 
questions before us on this matter. In the end, the most 
important conclusion to reach will be one that offers more 
effective screening and treatment options for women.
    This week I was pleased to join Senator Dianne Feinstein, 
yourself Chairwoman Mikulski and many of our other colleagues 
in co-sponsoring The National Cancer Act of 2002. It is a 
modernization and enhancement of the original National Cancer 
Act of 1971, which was a result of President Richard Nixon's 
``war on cancer.'' This legislation would increase funding for 
the National Cancer Institute (NCI), provide incentives and 
increased compensation for researchers and physicians, and 
improve and expand the recruitment and training of health care 
workers who serve in underprivileged areas and areas with high 
rates of cancer. A major provision of the bill would allow the 
NCI to fully fund 40 percent of the research grant applications 
received, which is considerably higher than the current level 
of 28%.
    In a time when cancer is claiming the lives of over 500,000 
Americans per year, and 1 in 8 women will develop breast cancer 
in the course of their lives, it is clear to me that we must 
continue to increase our investments in life-saving cancer 
research. Thank you for organizing these important hearings 
today, and I am looking forward to learning more from our 
witnesses. I know it will help us as we move to reauthorize the 
Mammography Quality Standards Act.

                Prepared Statement of Senator Hutchison

    Thank you, Mr. Chairman. I am glad we have the opportunity 
today to disseminate the correct information in regards to 
mammography. It is important for women to know that mammography 
is an important tool in our fight against breast cancer.
    I am a cosponsor on Sen. Feinstein's cancer legislation 
which was introduced yesterday. This legislation addresses the 
issue of mammography. It mandates that everyone has a right to 
receive a mammogram who is 40 years of age or older or is at 
high risk of developing breast cancer. We understand the 
importance of mammography enough to put it into legislation. It 
is our responsibility to further ensure that the public is 
encouraged to take the steps necessary to detect cancer at an 
early stage.
    I am concerned after reading the recent Washington Post 
(February 17th) article that women will not be encouraged to 
get a mammogram. The head of general medicine at a Seattle 
hospital stated that she was not pressuring women to have a 
mammogram. If there are questions or misinformation at that 
level of expertise, then what is the general public thinking? 
Women don't necessarily want to have one in the first place and 
if an ``out'' is presented to them, then they may take it.
    This is why I reiterate that it is important that we get 
the correct information out about mammography and that 
screening should start at 40. More than 2,600 women in Texas 
will be diagnosed with breast cancer this year and it would be 
greatly disturbing to have these numbers rise higher when we 
are just beginning to win the battle.
    I hope at this hearing today we clarify the issues for 
ourselves and the public.
    Senator Mikulski. We are now going to turn to our first 
witness, Dr. Andrew von Eschenbach, who is director of the 
National Cancer Institute at the National Institutes of Health. 
He is the 12th director of the NCI and comes as an academician, 
a scholar, a researcher, and a clinician. His area of expertise 
has been prostate cancer, but he has also been a consulting 
professor in the department of cancer biology at M.D. Anderson 
Cancer Center and has led a faculty of more than 1,000 cancer 
researchers and clinicians, as well as serving in the Navy. 
There are many things that can be said about his articles and 
his very hard work.
    We really welcome you, Dr. von Eschenbach. We are going to 
count on you for your expertise and your leadership on this 
topic.
    We will now turn to you. Thank you.

  STATEMENT OF DR. ANDREW VON ESCHENBACH, DIRECTOR, NATIONAL 
     CANCER INSTITUTE, NATIONAL INSTITUTES OF HEALTH, U.S. 
            DEPARTMENT OF HEALTH AND HUMAN SERVICES

    Dr. von Eschenbach. Thank you, Senator, and good afternoon, 
distinguished members of the subcommittees.
    I am very pleased to present my first official testimony as 
director of the National Cancer Institute and to do so on the 
important public health issue of mammography and to provide 
guidance on both the scientific and clinical dimensions of this 
problem, and to also make clear why the National Cancer 
Institute remains committed to its use of mammography as one 
tool in our fight against breast cancer.
    I ask that my full written statement be included in the 
hearing record.
    Senator Mikulski. Without objection.
    Dr. von Eschenbach. I am joined today by Dr. Peter 
Greenwald, director of the National Cancer Institute's Division 
of Cancer Prevention, and by Dr. Barbara Reimer, director of 
our Division of Cancer Control and Population Sciences. These 
two individuals have worked tirelessly on this issue and have 
contributed so much to our understanding of early detection 
strategies.
    Along with the millions of women threatened by breast 
cancer, we at the National Cancer Institute are grateful to 
you, not only for your addressing this issue today but for all 
the effort you have expended in the past to help make more 
effective early detection and treatment options available to 
women.
    As you know all too well, cancer is a complex disease, and 
our solutions to this menace are likewise complex but also 
deliberate. As scientists and clinicians, we examine, we 
evaluate, we learn, and we intervene, and through it all, we 
continue to drive forward toward our goal to save lives and to 
eliminate suffering.
    This has been the story with our continuing struggle 
against breast cancer. Many years ago, we embarked on this 
journey to save the lives of women with breast cancer by 
detecting the disease early, when we could apply more effective 
therapies. Our tool initially for early detection was breast 
examination to detect a lump; then, in the 1960's, x-ray 
detection using mammography began to be employed, especially in 
North America and Europe.
    From the 1960's to the 1980's, seven randomized clinical 
trials that enrolled over 400,000 women were conducted to 
determine whether mammography, when used as a screening tool in 
women with no symptoms or sign of breast cancer, would then 
result in decreased mortality from breast cancer.
    These data have been subsequently analyzed, examined, and 
reexamined by organizations like the National Cancer Institute, 
the American Cancer Society, the American College of Radiology, 
the U.S. Preventive Services Task Force, and many others. These 
reviews ultimately led the National Cancer Institute and the 
American Cancer Society to together issue a recommendation in 
1997 that mammography was beneficial to women in saving their 
lives from breast cancer, beginning with examination starting 
at age 40.
    As you have mentioned, Senator, a recent critique of these 
major clinical trials has reawakened the debate by casting 
doubt on the absolute value of mammography. While my written 
testimony provides more specific details, the bottom line is 
that the National Cancer Institute has reviewed this latest 
analysis and, after careful and serious deliberation, we have 
concluded that the weight of evidence continues to show that 
mammography saves lives through early detection, which permits 
treatment of the disease at an earlier stage.
    This conclusion is shared by the U.S. Preventive Services 
Task Force, an independent panel of private sector experts in 
prevention and primary care that is sponsored by the Agency for 
Health Care Research and Quality.
    Senators, allow me to be clear in my testimony. As the 
director of the National Cancer Institute, who is also an 
investigator, a clinician, and a cancer patient, I want to 
assure you and the women of this Nation that we are being 
vigilant regarding evaluation of all information on early 
detection of breast cancer; that we are dedicated to 
continuously improving the diagnosis and treatment of this 
disease to save lives; and finally, to reaffirm the following 
recommendation that, beginning in their forties, women should 
be screened for breast cancer with mammography every one to 2 
years.
    In my written testimony, I have provided you with detailed 
information regarding our vigilant examination and monitoring 
of the data, our insights into the debate among the experts, 
and I have enumerated many of the programs that are being 
sponsored by the National Cancer Institute to improve early 
detection and treatment of breast cancer.
    Today in my oral testimony, I would like to focus on what I 
believe is the crux of the issue. In this first chart, the 
women of this Nation need to know that while we are far from 
declaring victory, we are headed in the right direction. In the 
past 10 years, overall mortality rates from breast cancer 
continue to fall. We first saw this encouraging trend in 1989, 
with the decreasing death rate of 1.4 percent per year. More 
recently, the decrease has sharpened to 3.2 percent per year.
    There are significant declines for all ages, and this 
reduction in death rates has resulted over time in 38,000 saved 
lives. We have a long way to go, particularly to address the 
gap between white and black women. But we must ensure that as 
we go forward, this downward trend that we see here continues.
    There are multiple factors that can be attributed to this 
decline. We also need to understand that it is a complex 
interaction of both the value of early detection, namely, the 
application of mammography, and the application of better 
therapies that are being developed and applied to women who are 
diagnosed with breast cancer. This is an equation in which both 
factors leading to that decline are important. Experts may 
argue about the degree to which one of those factors may or may 
not be contributing to the outcome, but clearly, both factors 
are of importance, and both factors must remain in the 
equation, because without detection, treatment is not possible.
    At the same time, we must remember that we have to continue 
to focus on further downturn in that curve, and in that regard, 
we must continue to monitor information to determine better 
methods of early detection; we must at the same time contribute 
to more improved methods of therapy so that together, they will 
result in the most appropriate outcome that you have asked for, 
namely, that we save lives of women with breast cancer.
    I would like to once again reassure the women of this 
Nation that the National Cancer Institute stands today by its 
recommendation of mammography screening beginning in women in 
their forties, and that we are doing everything we can so that 
tomorrow, we can improve prevention, screening, treatment, and 
supportive care so that we will continue these encouraging 
trends in survival that we have seen over the last decade.
    I thank you for the opportunity to testify about this 
vitally important topic, and I will be pleased later to respond 
to your questions.
    [The prepared statement of Dr. von Eschenbach follows:]
           Prepared Statement of Andrew von Eschenbach, M.D.
    Good afternoon, members of the Subcommittees. I am Andrew von 
Eschenbach, M.D., Director of the National Cancer Institute (NCI). I am 
pleased to present my first official testimony as the new Director of 
NCI before these distinguished Committees on the very important public 
health topic of mammography.
    I would like to begin with a very concise summary of the position 
of NCI and the Department of Health and Human Services (HHS) on 
mammography and our current plans. I will expand on these later in my 
testimony. Let me assure you that NCI is collaborating with other 
agencies within the Department, including the Agency for Healthcare 
Research and Quality (AHRQ) and the Centers for Disease Control and 
Prevention (CDC), to ensure that together we are providing the latest 
science, clinical recommendations, and programs to prevent, screen, 
diagnose, and treat breast cancer.
    Breast cancer mortality continues to fall, and that is very good 
news. Death rates from breast cancer first began to decline in 1989 at 
1.4 percent per year. More recently the decrease has improved to 3.2 
percent per year. This is a significant decline for all ages. 
Unfortunately, the decline began later (1993) and is lower for Black 
women, whose breast cancer death rates are 33 percent higher than rates 
for all women.
    We feel confident that mammography has contributed to this decline, 
but mammography alone has not driven this trend. Advances in therapy, 
including adjuvant therapy (both hormonal and chemotherapy) and 
chemoprevention approaches (such as tamoxifen) have also played a role. 
Unfortunately, the current debate appears to be focused on this single 
component in the equation. What we need to keep in mind is that many 
factors taken together are responsible, all are important, and we 
cannot eliminate any from our current approach to breast cancer. Women 
need unimpeded access to prevention, screening, treatment, and 
supportive care to win their battle against breast cancer, and we need 
to keep our focus on the sum of the equation: longer life coupled with 
better quality of life.
    NCI continues to recommend mammography screening for women 
beginning in their forties. This is consistent with the recently 
released report of the U.S. Preventive Services Task Force (USPSTF), an 
independent panel of private-sector experts in prevention and primary 
care sponsored by AHRQ. On February 21, 2002, HHS Secretary Tommy 
Thompson released an updated recommendation from the USPSTF that 
recommended screening mammography every 1-2 years for women ages 40 and 
over. As Secretary Thompson stated, ``I believe that this 
recommendation reaffirms the importance of mammography and should 
substantially allay concerns about its value in safeguarding the health 
of women.''
    Everyone agrees that mammography detects early tumors when they are 
smaller, detects more tumors, and gives a woman more options for 
treatment. These benefits are substantial by themselves. The 
controversial issue is whether it saves lives in the long run. We have 
reviewed the evidence and the USPSTF recommendation, and we conclude 
that the weight of the evidence shows that mammography saves lives 
through early detection and treatment at an earlier stage. We will 
continue to monitor and consider any new information about mammography. 
However, mammography as a screening technology is only one tool, and we 
are pursuing a strong research agenda to develop other methods, such as 
improved imaging techniques, to design better ways to screen for breast 
cancer in the future. We will continue to work closely with other 
Institutes and Centers of the National Institutes of Health (NIH), 
organizations, and breast cancer patient advocates to ensure that 
research findings are translated quickly into effective interventions.
    How do we know what we know about mammography? The use of x-ray 
imaging for the detection of breast cancer came into use in the 1960s, 
following technological advances that resulted in better images that 
were easier to reproduce and interpret. Initially used to assist in 
diagnosis, mammography was also studied for its potential use as a 
screening tool. Several randomized clinical trials of mammography have 
been conducted since 1963, and as these studies have been completed and 
the data analyzed, the findings have added to the total body of 
evidence we have today. At various times in the past decades, different 
organizations such as the American College of Radiology, the American 
Cancer Society, NCI, and others have reviewed the available data on 
screening mammography, have drawn conclusions about the strength of 
that evidence, and have made recommendations or statements about its 
appropriate role and use. Specifically, in 1993 NCI convened a workshop 
of experts to examine the available literature and data on screening 
mammography and to issue a statement of the strength of that evidence. 
At that time, the NCI concluded that the evidence supported mammography 
for women over age 50 but not under age 50.
    In the intervening years, more data were obtained on the women who 
participated in the trials, and there were now enough women who had 
entered the trials in their 40s to more accurately assess the impact of 
mammography for women in their 40s. In 1997, there was a National 
Institutes of Health consensus conference where an extensive review was 
reported of all of the available information on screening mammography. 
Following that meeting and subsequent deliberations by our respective 
boards of advisors, both NCI and the American Cancer Society (ACS) 
released modified breast cancer screening recommendations. As of 1997, 
both NCI and ACS recommend mammography for women starting at age 40, 
although on somewhat different screening intervals. Both organizations 
also emphasized the importance of informed decision making about 
mammography.
    The critique by Olsen and Gotzsche that was published in The Lancet 
last fall reviewed the seven randomized clinical trials of mammography 
that were done in the 1960s through 1980s. They considered technical 
details of the trials, such as how women were randomized into 
mammography and control groups, and whether breast cancer as a cause of 
death was determined accurately. The authors found technical problems 
in five of the clinical trials, all of which had shown a reduction in 
mortality associated with mammography; they therefore called into 
question the value of mammography.
    The NCI has reviewed very carefully the Olsen and Gotzsche 
critique, and we have concluded that their review does not warrant a 
departure from our current recommendation on mammography. Over 400,000 
women took part in the seven randomized clinical trials that were 
reviewed by Olsen and Gotzsche. They examined each of these trials and 
identified potential flaws that could have influenced the findings in 
several of the studies. They gave little weight to the reported 
benefits from five of the seven trials and went on to conclude that the 
totality of evidence did not support screening mammography. However, 
difference of opinion among experts regarding design of these studies 
does not in itself prove that the conclusions are wrong. After careful 
deliberation of the arguments, the NCI has concluded that the value of 
mammography has not been refuted.
    Let me give you two examples of what Olsen and Gotzsche said and 
why we disagree. The first clinical trial of mammography was begun in 
New York City in the 1960s. It was state-of-the-art at that time. Olsen 
and Gotzsche pointed out that after the participants were randomized 
into two groups, one group to be screened and the other not to be 
screened, a larger number of women were excluded from the group to be 
screened than from the unscreened group. This suggested the possibility 
that women diagnosed with breast cancer before the study began could be 
included in the screened group, but not in the unscreened group, 
resulting in a bias that would make it appear that mammography was 
useful, when this might only have been an artifact of study design. A 
scientific clinical trials expert who worked on this trial corroborated 
that during the nineteen-year follow-up period, any woman with breast 
cancer diagnosed prior to the onset of the study was excluded from both 
groups. This would correct for the potential bias suggested by Olsen 
and Gotzsche.
    A second claim by Olsen and Gotzsche was that in several studies, 
the cause of death in the mammography screened group was more often 
called ``died with breast cancer,'' while in the comparison group, 
women were classified as ``died of breast cancer.'' They claimed that 
this could also be a bias in favor of mammography. However, this is 
also what you would see if mammography were in fact saving lives. 
Therefore, the NCI concluded that Olsen and Gotzsche have not refuted 
the evidence that mammography saves lives.
    The authors also failed to consider that since the time these 
trials were conducted, there have been improvements in mammography and 
the technique of biopsy as well as in treatment. We have learned much 
about breast cancer biology since this time--we now think that if 
tumors are detected when small in size, they have not yet developed 
many blood vessels, and are less likely to be aggressive or to 
metastasize. Mammography can detect these small tumors and also can 
detect the earliest form of breast cancer, called ductal carcinoma in 
situ, and surgery can remove these lesions.
    Olsen and Gotzsche's analysis is not the first one to scrutinize 
the underlying data in these studies. Other expert groups have 
conducted intensive reviews of the studies and have reaffirmed previous 
findings of a mortality reduction benefit, most notably the recent 
report of the USPSTF.
    Large workshops and consensus conferences have been convened in an 
attempt to reach agreement on what the data actually say, and we have 
all witnessed the difficulty and frustration that ensue from these 
efforts to both reach agreement on the meaning of the data and also to 
craft a statement that accurately reflects the meaning. Simply put, 
this is not an easy task, and the conclusions reached by Olsen and 
Gotzsche are at variance with other reviews by expert groups.
    The National Cancer Institute has compiled a very comprehensive 
database about cancer called Physician Data Query (PDQ), that contains 
the latest available information about cancer prevention, screening, 
diagnosis, treatment, genetics, supportive care, and clinical trials. 
Independent PDQ advisory boards have been retained by NCI to carry out 
periodic evaluations of the body of scientific data and its usefulness 
for drawing conclusions about the state of cancer care.
    At its last meeting, the PDQ screening and prevention editorial 
board discussed The Lancet review and felt that Olsen and Gotzsche made 
some valid points about the quality of the trials. However, no 
modifications to the current PDQ statement of evidence on breast cancer 
screening have been made at this time; we expect that specific 
recommendations will be discussed at the next meeting of the editorial 
board in March 2002.
                           what is nci doing?
    The NCI is committed to improving health outcomes for women with 
breast cancer. As part of the commitment, we will continue to strive to 
monitor new information as it emerges and to communicate what we learn. 
NCI has taken a number of steps to improve our effectiveness in these 
areas. First, I have asked two of NCI's division directors, Dr. Peter 
Greenwald, Director of the Division of Cancer Prevention, and Dr. 
Barbara Rimer, Director of the Division of Cancer Control and 
Population Sciences, to lead the new NCI Breast Screening Working 
Group. This group has three major tasks: one, to monitor and evaluate 
new information on mammography and how best to communicate the message; 
two, to monitor NCI's research program on imaging and molecular 
technologies for early detection; and three, to assess basic biology as 
it pertains to early detection (for example, molecular methods to 
differentiate indolent from aggressive tumors).
    Second, NCI has requested that the Institute of Medicine (IOM) 
review the evidence related to mammography and advise us on their 
interpretation of the evidence. This complements an ongoing initiative 
of the IOM to periodically update their year 2000 report entitled, 
Mammography and Beyond. This report examines the current state of the 
art in early breast cancer detection, identifies promising new 
technologies, and how best to move the field of breast cancer screening 
forward.
    Third, the NCI Breast Cancer Surveillance Consortium (BCSC), a 
cooperative agreement between the NCI and investigators at medical 
research centers across the country, is evaluating the performance of 
screening mammography in community practice in the United States. This 
research collaboration links data from mammography registries with data 
on cancer outcomes from pathology laboratories or cancer registries. 
The Consortium consists of eight research sites located in seven 
states, plus a Statistical Coordinating Center. As of April 2001, the 
Consortium's database contains information on 2.2 million screening 
mammographic examinations and 28,000 breast cancer cases. This is a 
tremendous resource that can tell us much more about how mammography is 
performed in community practice.
    The Breast Cancer Surveillance Consortium supports a wide-ranging 
portfolio of research projects that use population-based databases to 
evaluate the performance of screening mammography in community 
practice. Researchers at individual sites conduct analyses using data 
collected at their sites. In addition, all sites transmit their data to 
a centralized Statistical Coordinating Center located at the Group 
Health Cooperative site. This allows Consortium researchers to conduct 
analyses across sites using pooled data.
    Research in the Consortium examines issues such as the effect of 
breast density and hormone replacement therapy on the accuracy of 
screening mammography, the relationship of mammography assessment with 
final recommendations for diagnostic evaluation, biologic 
characteristics of breast cancers detected by mammography screening, 
and rates of detection of ductal carcinoma in situ among screened 
women. Anticipating the need to track the diffusion of new screening 
technologies in clinical practice, the Consortium is developing 
measures for tracking the use of digital mammography, which is a 
promising emerging technology, and will serve as a model for tracking 
the diffusion of other new technologies as they emerge.
           population data support a benefit for mammography
    In addition to data from clinical trials, we also have data from 
our population-based Surveillance, Epidemiology and End Results (SEER) 
registries that can be used to track new cases and deaths from breast 
cancer and to examine these in relation to changes in mammography use 
over time. NCI also has created a national collaboration of some of the 
Nation's leading statisticians, called Cancer Intervention and 
Surveillance modeling NETwork (CISNET), to examine important questions 
about trends in breast cancer and other diseases by using the latest 
modeling methods. Although preliminary, recent work by the 
statisticians leads to the following conclusion: breast cancer 
incidence rates by stage showed a decline of later stage disease and 
larger size tumors and an increase in smaller, early stage tumors and 
pre-invasive cancers. Modeling this shifting of cases to earlier tumors 
with better prognosis predicted a decline in mortality during recent 
years, accounting for about one-quarter to one-third of the observed 
decline in breast cancer mortality since 1990. The important fact is 
that back in the late 1980s, our statisticians predicted that if 
mammography rose over the next decade, there would be a subsequent 
decrease in mortality. We are now seeing that decrease.
                           beyond mammography
    There is no doubt that thousands of women are alive today because 
their breast cancers were treated successfully after having been 
detected by mammography. There also is no doubt that we have plenty of 
opportunity for improvement. We need better ways to detect breast 
cancer in its very earliest stages and to prevent its further growth. 
While mammography is the best technology we have available today, it 
has limitations. Tumors that exist, especially in dense breast tissue 
of younger women or located close to the chest wall, may be missed 
(false negative), while in other women there may be indications that 
cancer is present when it is not actually present (false positive), 
leading to a series of additional procedures such as repeat mammograms 
and/or biopsies. The debate about the role of mammography will continue 
until we have a better technology that more accurately predicts a 
woman's risk of developing breast cancer, and NCI is supporting a broad 
range of research on promising new approaches to breast cancer 
screening and early detection.
    Imaging research supported by NCI is advancing on several fronts. 
Along with efforts to improve conventional and digital x-ray 
mammography, NCI also supports research for several other technologies 
such as magnetic resonance imaging (MRI), ultrasonography, positron 
emission tomography (PET), and single photon emission computed 
tomography (SPECT). Already, with these technologies, scientists can 
``see'' and monitor biological processes taking place in living tissues 
such as blood flow, oxygen consumption, and glucose metabolism.
    A major research effort is under way to capitalize on the abundant 
discoveries in cancer biology and create imaging technologies that can 
noninvasively detect and display the actual molecular events taking 
place in the body. Molecular imaging will allow researchers to detect 
altered gene products and tumor-specific receptors or enzymes. The 
ability to visualize molecular pathways involved in the development of 
tumors is expected to enable researchers to detect and stage tumors 
more easily, to select more effective treatments, and to predict the 
effectiveness of new drugs. Some specific examples of research 
supported by NCI:
    Digital Mammography.--In 2001, the American College of Radiology 
Imaging Network (ACRIN), a group of researchers sponsored by NCI, 
launched the largest study ever to compare conventional and digital 
mammography. The Digital Mammographic Imaging Screening Trial, 
involving 49,500 women in the United States and Canada, will compare 
digital mammography to standard film mammography to determine how this 
new technique compares to the traditional method of screening for 
breast cancer.
    Magnetic Resonance Imaging.--An imaging modality making use of a 
magnetic field and radio-wave signals linked to a computer to create 
detailed images of areas inside the body without the use of radiation. 
Each MRI produces hundreds of images of the breast from side-to-side, 
top-to-bottom, and front-to-back. A radiologist then interprets the 
images. Breast MRI is not used for routine breast cancer screening, but 
clinical trials are under way to determine whether MRI is valuable for 
early detection in certain groups, such as young women at high risk for 
breast cancer and women with a previous history of breast cancer.
    Positron Emission Tomography.--PET creates computerized images of 
chemical changes that take place in tissue. NCI-sponsored researchers 
are evaluating the usefulness of PET to detect tumors in dense breasts. 
A clinical trial is also evaluating the usefulness of PET results 
compared with the findings from other imaging and diagnostic 
techniques. This trial is also studying the effectiveness of PET in 
tracking the response of a tumor to treatment.
    Computed Tomography (CT).--Computed tomography creates a series of 
detailed cross-sectional x-rays of areas inside the body taken from 
different angles. The images are then turned into two- and three-
dimensional pictures by a computer program. This technique is also 
called computerized tomography (CT) and computerized axial tomography 
(CAT). Several NCI-funded investigators are studying the use of 
dedicated breast CT devices as both a screening and diagnostic tool for 
the detection of breast cancer.
    Magnetic Resonance Spectroscopy (MRS).--MRS has the ability to 
distinguish cancerous tissue from normal tissue and benign growths. MRS 
can show the presence and relative quantities of the chemicals 
comprising tissues of each type, and can characterize even small 
tumors. As a result, MRS can make it easier to detect breast cancer at 
even earlier stages. A number of NCI grantees are exploring use of MRS 
in breast cancer.
    Optical Imaging.--Optical imaging refers not only to the use of 
visible light but also to radiation just beyond the visible--
ultraviolet and near-infrared. Several researchers are evaluating the 
potential of using visible or near infrared light to scan the breast 
for abnormalities alone and in conjunction with other imaging 
technologies and the possibility of combining such information with 
other techniques. For example, NCI is supporting projects that 
superimpose optical signals from small breast cancers onto MRI scans of 
the breast.
    Computer-Aided Detection (CAD).--CAD involves the use of computers 
to bring suspicious areas on a mammogram to the radiologist's 
attention. Through a number of grants, NCI is funding research that 
will develop computer-aided diagnosis methods to assist radiologists in 
diagnosing breast cancer from mammograms. It is hoped that CAD will 
improve radiologists' ability to interpret mammograms so that both the 
number of missed cancers and the number of women unnecessarily sent to 
biopsy can be reduced. A number of grantees are exploring the use of 
CAD in breast cancer. Currently, there are two FDA- approved CAD 
methods that are commercially available.
    Imaging Agents.--The NCI's Development of Clinical Imaging Drugs 
and Enhancers (DCIDE) program will foster and speed the development of 
promising imaging agents, such as contrast agents, and their 
translation from laboratory to clinic. NCI will make its pre-clinical 
development resources available to competitively selected developers of 
a promising diagnostic agent or probe in order to remove a recognized 
barrier between laboratory discoveries and their entry into the clinic. 
To further aid in the development of promising imaging agents, NCI is 
launching a program to fund early clinical trials of novel imaging 
probes and agents. One of the agents under development in this program 
is a nanoparticle that specifically targets angiogenic vessels. This 
could potentially play a role in cancer detection, staging, and 
monitoring of therapy for breast cancer.
    In addition to imaging technology, NCI is investing in new biologic 
tests to improve our ability to identify cancer cells in their earliest 
possible stages of development. Among the research being supported:
    Molecular Analysis.--NCI's Innovative Molecular Analysis 
Technologies Program (IMAT) supports the development of non-invasive 
techniques for identifying molecular changes that distinguish cancer 
cells from normal cells. More than 100 research projects are under way, 
focusing on new approaches to analyze DNA, RNA, and proteins.
    Proteomics: Finding Protein Patterns.--Proteomics is the systematic 
study of protein expression and function. In the Clinical Proteomics 
Program, a joint initiative of NCI and FDA, researchers are discovering 
differences in patterns of protein in the blood from cancer patients 
compared to people without cancer and applying this knowledge to early 
detection of breast cancer.
    Biomarkers.--NCI's Early Detection Research Network (EDRN) is the 
first comprehensive network to develop and validate early detection 
markers for cancer. Researchers are studying a variety of molecules, 
proteins, genes, and other biological substances that may be the 
earliest warning signs that normal cells are on the road to becoming 
cancerous. Their discoveries are then translated into methods for 
detecting warning signals, sometimes even before full-blown cancer can 
develop.
    Finding Fingerprints of Cancer Cells: The Molecular Classification 
of Tumors.--All cells have unique ``signatures''--special 
characteristics related to which genes are active and which proteins or 
other products the cell manufactures. During the transformation of a 
normal cell to a cancer cell, the cell's signature changes, and the 
change becomes a signal of the presence of cancer. Researchers are 
developing profiles of molecular alterations in human tumors, such as 
breast cancer, using DNA, RNA, or protein-based technologies. This 
technology holds promise for improving the early detection, diagnosis, 
and treatment of cancer.
    Over the years, researchers have focused on examination of cells 
shed by breast tissue into the ducts. Investigators have now developed 
techniques for collecting nipple aspirates and ductal lavage and hope 
that it may be possible to evaluate suspicious breast masses detected 
by mammography by analyzing these secretions. It may be possible to 
spare at least some women the need to undergo a surgical biopsy.
    These are by no means established techniques, and it would be more 
accurate to say that they are being ``explored'' rather than ``used'' 
in breast cancer diagnosis. There are now a number of investigators 
around the country who have methods that enable them to collect these 
specimens, but there is no consensus yet on how they should be 
analyzed. The NCI is currently funding research through its exploratory 
grant programs to determine which substances or characteristics of 
cells present in these specimens will correlate reliably with the 
presence of absence of cancer in the breast. The research also includes 
development of new analytic technologies to detect particular 
alterations. This research has not yet progressed to a stage where 
large-scale clinical trials are ready to proceed.
    NCI also supports a number of resources for the research community 
ranging from tissue banks to registries to shared funding for national 
monitoring programs.
                    communicating about mammography
    It is not enough to make discoveries. We also must turn those 
discoveries into interventions that benefit people and communicate that 
information so women can use it to make important decisions about their 
health. The investments that NCI, ACS, CDC, and AHRQ made in the 1980s 
and 1990s led to effective interventions to enhance use of mammography. 
There is a solid armamentarium of effective interventions, and we have 
seen the former Black-white differences in mammography use disappear. 
There still is under-use of mammography among some groups, including 
older and Hispanic women. We are now working with the CDC, ACS, and 
other organizations to disseminate the effective interventions.
    NCI has several projects in place to improve the ways we 
communicate the results of research and to take advantage of new 
communication technologies. One example is a research project funded by 
NCI and AHRQ studying how to communicate about the benefits and 
limitations of screening tests. Researchers are also developing tools 
to help women ask the important questions and to examine their own 
preferences. These research efforts are exploring the capacity of new 
communication technologies, including online and other interactive 
health communication tools, to address women's questions.
                               conclusion
    Multiple factors come together in an equation that leads to longer 
and better lives for breast cancer patients. All of our current tools 
are important, and all must be improved because the outcome, although 
better than in the past, is not yet what it should be. We must retain 
what is adequate and appropriate but strive to discover what is better. 
Many of the new technologies now under development hold real promise. 
Detecting the molecular changes that lead to cancer will give us the 
opportunity to intervene in the disease process more effectively. Like 
you, I am impatient for these new approaches to prove themselves. The 
lives of our mothers, daughters, wives, sisters, and friends are at 
stake. We cannot allow ourselves to become complacent, accepting the 
status quo. Yet, we must not ignore the fact that our best available 
technology today, mammography, does save lives.
    I thank you for this opportunity to testify about this vitally 
important topic. I will be pleased to respond to your questions.

    Senator Mikulski. Thank you very much, Dr. von Eschenbach.
    I just want to be sure--it is the National Cancer 
Institute's position that women should continue to get annual 
mammograms starting at age 40?
    Dr. von Eschenbach. Every one to 2 years, Senator, is our 
recommendation. Whether there is a difference between every 
year or between one and 2 years is still not absolutely 
determined, but at least every one to 2 years.
    Senator Mikulski. Thank you.
    You are familiar with the Danish study done by two very 
eminent biostatisticians. Because of logistics, they could not 
come today, although we acknowledge the cooperation of the 
Danish Embassy, and with unanimous consent, I am going to enter 
their study into the record.
    [Document follows:]

    [GRAPHIC(S) NOT AVAILABLE IN TIFF FORMAT]
    
    
    Senator Mikulski. My question is this, Doctor. You have 
read the Danish study of Drs. Olsen and Gotzsche, and also the 
PDQ, which is really an advisory board to the NIH and NCI, has 
also raised yellow flashing lights. Could you give us your 
comments and analysis of the Danish study, and if you care to 
comment on PDQ, from which a board member will testify later. 
You have just said it clearly, and the position has been 
clearly since 1997. We welcome your commentary on these two 
studies that essentially dispute what you have just said.
    Dr. von Eschenbach. In summary, the investigators that you 
address looked at the seven randomized trials, made decisions 
about certain aspects of those trials in terms of how much they 
would weight them or include them in a combined analysis of the 
information called the meta-analysis. Based on their judgments 
and decisions about the relative value of some of those 
studies, they eliminated some of them from the ultimate 
analysis. Then, when they applied their meta-analysis, they 
concluded that the information was not significant enough to 
warrant continued support of mammography.
    Other statisticians, other experts, have looked at their 
analysis and have raised concerns about many of the judgments 
that they made on a statistical basis. So there is a difference 
of opinion among the experts as to how one should evaluate 
those seven combined trials.
    Other experts have looked at that information and have 
concluded, as the U.S. Preventive Services Task Force has, that 
the data still supports the value of mammography in the 
equation that I pointed out and must continue to remain an 
important part of that equation.
    So the issue here, Senator, is a difference in statistical 
interpretation and methodology. From the scientific 
perspective, there is value in that argument. From the clinical 
perspective, however, one must conclude that there is no 
indication that mammography should not be in that equation 
based on that analysis, even if you might want to argue whether 
it is providing the major part of that equation or a component 
of it.
    Senator Mikulski. Doctor, I have time for one more 
question. Essentially what you are saying is that one group of 
biostatisticians came to one set of conclusions and another has 
come to another, both competent people.
    Dr. von Eschenbach. Correct.
    Senator Mikulski. We are now again into lack of clarity--I 
am not saying from you--and my question is do you think--there 
have only been seven studies over 40 years in terms of the 
efficacy of mammograms in early detection--do you think it is 
time to do another study?
    Dr. von Eschenbach. No, I do not.
    Senator Mikulski. Could you comment on that, because it 
would then seem like we need a study to settle the disputes 
about the other studies.
    Dr. von Eschenbach. Those studies over that period of time 
enrolled over 400,000 patients, and over that period of time, 
much has changed with regard to the State of the art of 
mammography and our State of the art with regard to breast 
cancer care.
    To attempt to repeat that kind of study in which there 
would be a randomization whereby women by the flip of a coin or 
by chance would be assigned to either mammography or no 
mammography would not at this point in time be a viable or 
rational study, in my opinion, one that would not likely be 
able to be carried out at this point in time and certainly not, 
I believe, under our current structure.
    Senator Mikulski. But, Doctor, isn't that true of any 
clinical trial? Some get the treatment, and some do not; some 
get the diagnosis, and some do not.
    Dr. von Eschenbach. In terms of being able to attract a 
sufficient number of patients to the trial and in terms of 
being able to get them to accept a randomization by the flip of 
a coin as to whether they would or would not get mammography, I 
have and I believe others have serious concerns that that kind 
of trial could not effectively be carried out in a reasonable 
period of time to get a conclusive answer to the question; 
while in the meantime, where we believe we should be focusing 
our efforts is on even better methods of detection than 
mammography and to look at newer technologies and their 
applications in the kinds of clinical trials you are 
describing.
    Senator Mikulski. You raise a very good point. 
Unfortunately, my time is up. I think other of my colleagues 
will raise other issues. But I thank you; I think we are on our 
way to clarification.
    Senator Harkin?
    Senator Harkin. Thank you, Senator Mikulski.
    I have looked very carefully at the study that was done by 
Olsen and Gotzsche, and it seems to me that first of all, these 
were mammographies that were done in the 1960's and 1970's and 
maybe in the early 1980's. I do not know if they got into the 
1980's or not, but it was sometime in that time frame. As you 
have stated, we clearly have better mammography technologies 
now than we had at that time.
    Second of all, Olsen and Gotzsche, as I understand it, 
looked at the technical details of how the studies were set up. 
If I am not mistaken, others have looked at their study and 
basically refuted some of their findings based upon what 
happened later on in the clinical trials. I am sorry, I am just 
a layman speaking here--I am not a doctor or a biostatistician 
or anything like that. But it seems to me, as I read through 
their study, that Olsen and Gotzsche, looked at one part of the 
data from the clinical trials, and based upon that, they said 
there was not conclusive evidence of the value of mammography. 
They did not really look at all the data. At least, that is my 
layman's way of interpreting it. And based upon some 
statistical analysis they had done about how the groups were 
selected and who was screened and who was not screened, they 
reached these decisions. But they did not take into account 
that those things were adjusted for, if I am not mistaken, 
later on. Those anomalies, whatever they might have been, were 
adjusted for later on.
    Am I somewhat correct in that?
    Dr. von Eschenbach. Yes, Senator, you are quite on track 
with regard to your interpretation, as I also see it, and I 
believe that on the next panel, there will be experts far more 
sophisticated than I with regard to biostatistics. But I am in 
agreement with your interpretation.
    Senator Harkin. I know that to the general public this 
sounds like a lot of gobbledegook, and it is sometimes beyond 
my comprehension, too. But if you read the Danish study and 
really get into it, I am finding out that they just looked too 
narrowly at the data from the clinical trials. Second, they did 
not take into account the new technologies and the development 
of better mammography screening that we have today.
    Now I want to follow up on what Senator Mikulski was just 
getting to when her time expired. She spoke about future 
methods of breast cancer screening and new types of 
technologies. Could you elaborate a little bit on that and 
perhaps the time frame we are looking at?
    Dr. von Eschenbach. At the present time, the National 
Cancer Institute is supporting one trial that is looking at the 
value of digital mammography versus standard mammography as a 
method of improved detection. Other technologies that are being 
evaluated include PET scanning, or the use of positron emission 
tomography, and the evaluation of the function of lesions; 
magnetic resonance imaging is also being employed; and 
techniques whereby we are beginning to understand the biologic 
basis of tumors; even aspirates from the nipple that enable us 
to look at cells may be a way of detecting cancer in its 
earlier stages.
    So there are multiple methodologies that are being 
evaluated in the kinds of trials that Senator Mikulski is 
referring to.
    Senator Harkin. Dr. von Eschenbach, the National Cancer 
Institute recently announced the development of a new blood 
test--for detection of ovarian cancer. I believe it is a blood 
test that patients can take.
    Dr. von Eschenbach. Correct.
    Senator Harkin. Is there anything underway in terms of 
research that might lead to some kind of blood test for early 
detection of breast cancer?
    Dr. von Eschenbach. Well, that is one of the methodologies 
that, as it is validated in ovarian cancer, needs to be more 
broadly applied, and the underlying technique certainly opens 
up the hope that this would be applicable to many cancers, 
including breast.
    Senator Harkin. Of course, the ultimate goal of all the 
money that we have been putting into breast cancer research is 
to hopefully find a means of prevention, a vaccine or some 
other treatment that would be a preventive measure for breast 
cancer. Is there anything along those lines that you can tell 
us about?
    Dr. von Eschenbach. I think that what we are looking at, 
Senator, in that equation is that we would like to attack this 
problem at multiple places along the spectrum, including the 
ability to prevent it. We now know that there are agents that 
have been developed that can be preventive for breast cancer; 
tamoxifen and relaxifen are being clinically tested, and new 
drugs are also being developed that would perhaps have less 
toxicity, yet at the same time be able to provide that 
preventive effect as well.
    So I want us at the National Cancer Institute to have a 
multipronged attack or approach that looks at detection, 
diagnosis, treatment, and prevention, so that ultimately, we 
eradicate the deaths that we are seeing from this disease.
    Senator Harkin. Thank you, Doctor.
    Senator Mikulski. We have now been joined by Senator Bill 
Frist, the only physician currently serving in the U.S. Senate, 
who has brought such keen insight to all of our committee 
deliberations and is the ranking member of the Public Health 
Subcommittee.
    Senator Frist, I would like to turn to you. Senator Specter 
was here, but he had a meeting with the Steel Caucus with the 
President, and Senator Snowe was unable to come. So we are glad 
to see you.
    Senator Frist. Thank you. I would just ask that my opening 
statement be made part of the record, and I apologize for being 
a few minutes late.
    Senator Mikulski. Without objection.
    [The prepared statement of Senator Frist follows:]

               Prepared Statement of Senator Frist, M.D.

    During the past few weeks, there have been seemingly 
conflicting and often confusing reports about the benefits of 
mammography screening. I believe today's hearing will go a long 
way toward providing more clarity. It is important that women 
have as much credible information as possible about mammography 
as a breast screening tool so that they can make informed and 
appropriate decisions about their health.
    I want to extend a special welcome to Dr. Andrew von 
Eshenbach of the National Cancer Institute. I understand that 
this is your first time testifying before Congress. I am very 
pleased that you are here today.
    It is confusing for many Americans to read a report in the 
local paper 1 week about a recent study stating that 
mammography may not be beneficial, and then to read statements 
by public officials the next week stating that the government 
still recommends mammographies. Women can easily be confused 
about what they should be doing in the interest of their own 
health.
    In many ways, it would be easier to communicate with the 
public about how to take care of their health if there existed 
one static, scientific document which stated exactly what 
should be done, by whom, at what time, and at what place. 
However, science is a constantly evolving field, with new 
information being added daily regarding new therapies and new 
ways of looking at diseases. As we gain more information about 
how to diagnose, treat, and or even cure many illnesses, we 
must interpret new research, evaluate it in the context of 
other studies, and challenge our scientific and medical 
assumptions.
    Unfortunately, making the right health care choices becomes 
particularly difficult when there are conflicting research 
studies. During those tumultuous times, we generally rely on 
public health and health care experts to assist us in wading 
through the information and drawing appropriate conclusions, to 
provide guidance to the general public about appropriate health 
care choices. For mammography, the story is no different. 
Scientists and statisticians have been debating the relative 
merits of mammography as a screening tool for a number of 
years. In the mid-1990's, for example, there was a great deal 
of controversy over whether women in their 40's should receive 
mammographies. After more definitive studies became available 
and were analyzed, the National Cancer Institute eventually 
decided to recommend screening for women in their 40's.
    Last fall, the issue once again came front and center when 
Danish scientists reviewed seven leading studies of mammography 
screening and concluded that there were significant questions 
about the quality of the research--ultimately questioning 
whether using mammography as a screening tool results in a 
reduction of breast cancer deaths. This one study produced a 
flurry of discussions about the validity of mammography as a 
screening tool and the message that we should be sending to 
women about its value. However, as is the case with all 
studies, research must be put in the context of what has 
already been learned.
    That is why I was encouraged when the U.S. Preventive 
Services Task Force, an independent panel of experts in primary 
care and prevention that systematically reviews the evidence of 
effectiveness and develops recommendations for clinical 
preventive services, last Thursday released new recommendations 
regarding mammography, based on a review of eight randomized, 
controlled trials. These recommendations call for screening 
mammography with or without clinical breast examination, every 
two years for women ages 40 and older, as well as clarifying 
recommendations regarding breast self examinations. Their 
previous recommendations, in 1989 and 1996, endorsed 
mammography for women over age 50.
    Although the Task Force's recommendations provide guidance 
about the overall value of mammography for breast cancer 
screening, it does not endorse mammography as the perfect 
screening tool. We need continued research to improve the 
detection of breast cancer lesions and differentiation between 
cancer lesions and other non-cancerous lesions. Moreover, as 
better diagnostic tools to detect early-stage tumors are 
developed, additional research will be needed to guide our 
decisions about recommended treatment options. Finally, as we 
all are aware, the answer is not just to detect breast cancer 
but also to both prevent the incidence of the cancer and to 
appropriately treat any detected tumors. We must work to not 
only diagnose, but also to prevent and cure the diseases.
    Additionally, we must continue efforts to ensure that women 
receive quality mammography services without reducing access to 
those services, which is why it is important that we strengthen 
the Mammography Quality Standards Act (MQSA). I appreciate the 
testimony from the National Breast Cancer Coalition and the 
Susan G. Komen Foundation about this vital program, and I look 
forward to working with Senator Kennedy, Senator Gregg, Senator 
Collins, and my other colleagues on this Committee to 
reauthorize this important law.
    Senator Frist. First of all, welcome, Dr. von Eschenbach. I 
know this is your first hearing. The position that you have 
assumed is one that is very, very important to millions and 
millions of Americans, as you well know. I appreciate your 
sacrificing a practice of taking care of patients one-on-one 
for public service, for what is a terribly important position 
and initiative. Whether it is in the Patient Bill of Rights or 
coverage of clinical trials for cancer or for preventive 
medicine or for Medicare reform modernization, what we do with 
cancer is right at the center of all of these debates. I am 
delighted to have you before us today, initiating that 
discussion, so people can get to know you and you can get to 
know them.
    You and I have had the opportunity to talk about a number 
of issues. Mammography is an issue that we are spending a lot 
of time on today and a very important issue that, as has been 
mentioned, has been debated and discussed again and again--we 
are going to continue to discuss it to find just the 
appropriate place. As I can see from your chart, we see the 
change in mortality and the various parameters that are there. 
A and B will continue to change, as will C, over time, and that 
is the importance of these hearings.
    In my couple of minutes, let me just ask you to expound a 
bit on translational research. I think it is very important--
and I know that you feel very strongly about it--to make sure 
that the basic research findings that are so remarkable, that 
we have invested in in a doubling fashion at the National 
Institutes of Health, are translated into the types of 
diagnostic and treatment procedures, like mammography, like 
treatment for breast cancer.
    Could you share with us a little bit of your philosophy and 
what you hope to see happen; feel free to use mammography as an 
example of the importance of translational research.
    Dr. von Eschenbach. Thank you, Senator. I would be 
delighted to share that with you, and I think that breast 
cancer is a very important example of the opportunity and the 
challenge that translational research provides us.
    Specifically, one of the problems with mammography is the 
question as to whether we are detecting some breast cancers 
that, by their very nature, would not be virulent or aggressive 
and would then threaten a patient's life.
    We do not yet have a way of being able to accurately, 
totally, completely determine or predict that, so we must treat 
any cancer that we find as a dangerous cancer requiring 
significant intervention.
    Hopefully, as we begin to understand how cancer cells 
develop at the genetic level and why they behave the way they 
do based on their interactions with other cells, when we 
understand that at the basic, fundamental, biological level, we 
can design interventions that can interfere with, change, or 
alter that behavior, and we may then be able to use that 
information to define the aggressive cancers, treat them 
aggressively, to find the cancers that do not have those 
molecular-genetic characteristics and treat them in a more 
benevolent but effective fashion.
    So translational research will significantly improve the 
rational application of our treatments.
    Senator Frist. And what will that do to the protocols, and 
what can be recommended? How will that change those protocols?
    Dr. von Eschenbach. One of the important ways that I think 
it will change the protocols is that before a patient enters 
into a protocol, we can use the molecular and genetic 
information to stratify them, if you will, to separate them 
into high-risk and low-risk groups and then apply the 
particular treatment strategy or the protocol that we are 
testing; but we will know much more precisely the basis upon 
which we are gathering that information.
    Senator Frist. Thank you.
    Madam Chairman, I think I will forego; I know we have a 
number of other panels to hear from.
    Senator Mikulski. Thank you very much, Senator. That was an 
excellent question.
    I would now like to turn to Senator Jack Reed.
    Senator Reed. Thank you very much, Madam Chairman.
    Thank you very much, Doctor, for your testimony. At the 
core of today's hearing is a controversy about the efficacy of 
mammography in screening. Stepping aside from that, besides the 
advice that you are giving women today to continue the 
screening, is there other advice that you might give in terms 
of perhaps starting younger in terms of screening, or a 
different approach to it that would avoid the question of the 
efficacy of the tests and the statistical debate we are having 
today?
    Dr. von Eschenbach. No, Senator. We set the threshold at 40 
as what we believe to do the optimal or reasonable level at 
which we can recommend it and apply it. Now, again, the 
research that I alluded to earlier in terms of understanding 
the disease will hopefully lead us to be able to identify women 
who are at much higher risk than normal or average, and in 
those women, we may need to modify or change the 
recommendations as we go forward so we can detect them even 
sooner or earlier. But that is a work in progress, and we have 
not yet reached the point where we can make it a uniform 
recommendation.
    Senator Reed. You have experience in several different 
medical conditions, cancer, etc. Is there a similar controversy 
in other areas, for example, in terms of prostate or other 
cancers, where the testing regime and the efficacy are also 
debated as they are with mammography?
    Dr. von Eschenbach. Yes, sir, unfortunately, there are, and 
I personally was deeply involved in the issue of formulating 
guidelines for men for the use of prostate-specific antigen. As 
with mammography, in that situation, there is even less data or 
information upon which to make hard, specific, scientific 
recommendations.
    I think what we are faced with as clinicians responsible 
for the lives of patients with cancer is to apply the science, 
but at the same time use clinical judgment and arrive at the 
best recommendation we can today given the information that we 
have.
    The information on mammography is far better than the 
information for PSA and prostate cancer, and we are basing our 
recommendation to American women on what we have available as 
the best information.
    Senator Reed. But I would suspect that both of these areas 
have helped in terms of your analysis, that having experience 
in several different fields has helped inform your judgment 
about your recommendation today.
    Dr. von Eschenbach. What is most gratifying to you and to 
us is the fact that in both of these diseases, we are seeing a 
decline in mortality; we are seeing a decline in death rate. 
That gives us hope and a bit of comfort that we are at least on 
the right track. We are nowhere near where we need to be, but 
we are heading in the right direction.
    Senator Reed. Finally, Doctor, you indicated in your 
testimony the disparity between the incidence of in African 
American women and white women, Caucasian women. What role does 
mammography play in this disparity, and what might be other 
contributing factors?
    Dr. von Eschenbach. There are two very interesting 
observations that can shed some light on the answer to that 
question. One is that we are beginning to see the gap narrow 
between the mortality rate for black women and white women, so 
we are improving, we are closing that gap, and we are making 
progress. That coincides with the fact that there has been 
greater utilization of mammography among black women. So that 
hopefully, those are coincident. I cannot prove them to be 
cause and effect, but they are coincident, and they are both 
encouraging.
    Senator Reed. Thank you. One final point, Doctor. I do not 
know much about South Philly, but are you the only von 
Eschenbach in South Philly?
    Dr. von Eschenbach. My mother's maiden name was de Alfonso.
    Senator Reed. Now I understand, now I understand. Thank 
you, Doctor. The record is now complete. I yield back.
    Dr. von Eschenbach. Thank you, Senator.
    Senator Mikulski. Senator Murray?
    Senator Murray. Thank you very much, Madam Chairman, first 
for having this hearing, which I think is so important today, 
but also for your long-time work on the issue of breast cancer. 
We have been here before, debating this issue--Senator 
Hutchison remembers--and frankly, we have been through it too 
many times, and I think the bottom line is that women need to 
know what they can do to fight breast cancer, and 
unfortunately, this debate too often comes down to a debate 
between numbers versus women, and we have allowed abstract 
statistical data to confuse and distort the issues.
    I want to thank all the witnesses who are here today, 
especially the advocates, for the tremendous work that you do 
on behalf of so many women. I appreciate your continuing 
efforts to make sure that women have access to early screening 
and diagnosis.
    Madam Chairman, it seems to me, unfortunately, that we have 
allowed this controversy to shift the focus away from 
prevention and access to health care. This is not just an issue 
for women in their 40's or 50's, but for women who are in their 
20's and 30's who want to know what they can do today to 
prevent breast cancer. I hope we do not lose our focus on that 
issue.
    One issue that concerns me very much is that we do know 
that through better information and access, more women are 
getting regular mammograms, and we know that that has helped to 
boost survival rates; but we also know that access has not 
improved equally across the board for all women. Minority women 
have a much lower screening rate; in fact, the screening rate 
for Asian and Native American women is really dismal. I know 
there are many factors that contribute to those low rates, but 
I am very worried that the current conflicting and confusing 
messages are not going to help our efforts to expand access.
    Doctor, if you could just tell me what you think we need to 
do to make sure that this current controversy does not hinder 
our efforts to improve access for minority women, I would 
appreciate hearing your thoughts on that.
    Dr. von Eschenbach. Thank you, Senator Murray.
    We have tried to be very clear in our message so that we do 
not continue to contribute to some of the concern. At the same 
time, we are paying a great deal of attention within the 
National Cancer Institute, particularly through Dr. Reimer's 
division, to messages and communication and education so that 
patients do in fact have appropriate and timely and accurate 
information; and we are learning and studying how to reach out 
as effectively as we possibly can to various communities so 
that we can provide that appropriate message in the appropriate 
way.
    Senator Murray. I think that that is extremely important to 
do. Especially when information that comes out that is 
conflicting, it automatically offers women the excuse that they 
are looking for. So I think we need to especially now, at times 
like this, reach out again and make sure we are doing and 
saying what we need to do to make sure that women get screened.
    Let me ask you another question. We always focus on what 
age do you start having a mammogram every year, and we need to 
really get that message out; it is very important. But I am 
also very concerned about what we should be telling women who 
are in their 20's about what they can do now, before they start 
worrying about getting a mammogram when they are 40. What are 
we learning today that women can be doing even when they are 
young teenagers that will help decrease their risk of getting 
breast cancer?
    Dr. von Eschenbach. Well, we do not have the absolute cause 
and effect kinds of relationships where we can say that if you 
absolutely do this, we can guarantee that you will not have a 
problem. But we do recognize certain associations--for example, 
diet being one of them--and we are obviously encouraging a 
healthy lifestyle with regard to diet and exercise as part of 
that preventive process.
    What we need to do is research that will help us identify 
women who are at high risk early in life and also identify the 
most effective preventive methods, not just in terms of 
lifestyle but some of the biologic interventions that are safe 
and appropriate. Our whole area of cancer prevention is 
directed toward trying to identify those kinds of interventions 
and then apply them appropriately in women at high risk.
    Senator Murray. Good. I really appreciate that, and I hope 
that we do not allow these kinds of discussions to refocus away 
from making sure that we are doing that, because I really think 
that that is the much better answer in the long run, what we 
can do when we are younger so that breast cancer is not such a 
concern for women who are older.
    I have one other comment and question. I think there is 
another issue that has really been ignored in this debate, and 
that is the role that mammography has played not just in 
improving survival rates but in improving quality of life for 
breast cancer victims. The written statement of Dr. Leffall, 
who is the chair-elect of the Susan G. Komen Breast Cancer 
Foundation, shows that because of mammography, tumors have been 
detected earlier and smaller.
    Now, that is a huge benefit that I think has been lost in 
this debate, because options to mastectomy significantly 
improve quality of life and allow for a faster and quicker 
recovery.
    Can you talk a little bit about how mammography and early 
diagnosis have impacted quality of life for breast cancer 
patients?
    Dr. von Eschenbach. Thank you for pointing that out. I 
think that from the quality of life point of view, over and 
above just the mortality argument or discussion that we have 
been having, from the patient's point of view, that is an 
extremely important contribution. By detecting cancers earlier, 
one can then apply therapies that are going to be less 
mutilating and have less of an impact on quality of life, and 
that in itself is a major goal and objective for us. So I 
concur completely with your emphasis on that particular aspect 
of the issue.
    Senator Murray. Thank you very much, Doctor. I really 
appreciate your coming and providing the testimony today.
    Madam Chairman, again, I really want to thank you for 
holding this hearing to clarify this issue once again and to 
help us focus on what we can do to make quality of life better 
for all women in this country.
    Senator Mikulski. Thank you very much, Senator Murray, for 
your compliments but most of all for your ongoing advocacy.
    I invited the two Republican women who are not on the 
committee to join us today because of their longstanding 
advocacy on this issue. As I said, Senator Snowe and I have 
worked on this since we were in the House, but Senator Kay 
Bailey Hutchison is here, and Doctor, you will be interested to 
know that the women of the Senate have really worked on women's 
health on a bipartisan basis and particularly on the issues of 
breast and ovarian cancer. Senator Kay Bailey Hutchison has 
been an advocate in helping me get the Mammogram Quality 
Standards that were necessary, and of course, she is from the 
home State of the outstanding Komen Foundation. And also, you 
are on the Labor-HHS Committee on Appropriations, so you are 
also a member of this. I am sorry.
    Senator Hutchison. That is right, Madam Chairman, and you 
and I, of course, have worked on many cancer issues and trying 
to fund cancer research.
    But to give you the real background--I feel like it is deja 
vu all over again--in 1994, the Government representative came 
forward and said women should not have mammograms until they 
are 50. Well, Senator Mikulski called a hearing, and every, 
single woman Member of the Senate came and upbraided the 
Government official, who was sitting at that table by himself 
just like you are, and said how could you send this kind of 
mixed message. We have been working for years now to at least 
get early detection for women, because that is all we have--we 
do not have the cure--and finally, after about a month or so 
after that hearing, the entire NCI cratered, and everybody 
said, ``No, no, no--40--we think that is probably the most 
prudent thing to do. Women should have mammograms at the age of 
40.''
    Well, fast-forward to about a month ago, and we see the 
results of the study that say that mammograms are really 
useless and might even cause harm. I was looking at that, just 
astonished that we could be once again mixing our message based 
on, apparently, trials that were done in 1985. Now, there may 
have been other things that went into that, but we are talking 
about 1985 trials, and we are saying, well, you can do without 
a mammogram, and maybe walking is just as good as getting a 
mammogram.
    Well, here we are again, and Dr. von Eschenbach, I am so 
glad that you have clarified very quickly that 40 is the 
recommendation, because I know that we have saved lives. 
Everyone in this room knows that by early detection, we have 
saved lives. We also have put hundreds of millions of dollars 
into research to try to find the cure, and you will be in a 
pivotal position to help us find that cure so that we will not 
have to talk about mammogram anymore; we will cure this, and 
then perhaps we will not have to deal with cancer of this kind 
again, and we can move on to something else.
    But for now, I would ask you how you view this study that 
is based on these 1985 trials that came from the Danish 
researchers that would indicate that false positives are a 
reason not to go forward and do the only thing we know that 
will allow the early detection of a cancer tumor.
    Dr. von Eschenbach. There are two answers that I might 
offer, Senator. One is that certainly as we have improved the 
technology of not only mammography, but the ancillary studies 
that can be used to follow up mammography, including the 
ability to biopsy under ultrasound, we have actually been able 
to improve on the false positive concern, if you will.
    So I think that additional progress is improving some of 
those previous concerns and issues.
    The other thing that I think your question comes out, to 
come back to my example, is that we are seeing a decline, and 
if you want to use the number 6 per 100,000 as that decline, 
one could--and I think the debate has been around whether it is 
3 plus 3 equals 6, or 2 plus 4 equals, and there is an argument 
around the relative value of mammography--but I believe we all 
conclude that mammography needs to be a part of that equation, 
that it is continuing to add to that equation, and whether 
there is an argument among statisticians as to whether it is 3 
plus 3 or 2 plus 4, the important point is that it is 
contributing and must remain a part of the equation.
    Senator Hutchison. Anyone who has had a mammogram knows 
that you wonder which is worse--getting the mammogram or 
getting the cancer--but having said that, is there anything 
harmful that can be done in a mammogram, or maybe a wrongly 
given one, but is there in general a harmful effect of a 
mammogram?
    Dr. von Eschenbach. I believe that the greatest issue is in 
fact the discomfort and the humiliation that may go along with 
the examination, but other than that, other harms would be 
negligible, in my opinion.
    Senator Hutchison. Well, thank you, and I do hope that you 
will use your position to help us find the cure, because that 
is what has been missing for all these years that we have 
worked to try to eradicate breast cancer as a leading cause of 
deaths among women.
    Thank you.
    Dr. von Eschenbach. Thank you, Senator.
    Senator Mikulski. Now we turn to Senator Clinton, one of 
the newer members of the committee but certainly one of our 
most active.
    Senator Clinton?
    Senator Clinton. Thank you very much, and thank you for 
holding this hearing.
    And thank you, Dr. von Eschenbach, for now being in the hot 
seat for quite some time. I appreciate your clarification--I am 
sorry that I missed your testimony, and I just want to ask 
three brief questions just to be sure that I can accurately 
report to my many constituents who are deeply concerned about 
the controversy and also about the high prevalence of breast 
cancer in many parts of New York, higher than the national 
average.
    Is it fair to say that your testimony today reflecting the 
NCI position is that all women should get regular mammograms 
after the age of 40, or is it that women should be provided 
with information about the benefits and risks which they then, 
in consultation with their doctors, make their own decisions?
    Dr. von Eschenbach. We are recommending that it be a 
combination of both the performance and availability of the 
mammogram along with the education and understanding of the 
implications of it. I believe that both of those are important, 
but I would not leave out the mammogram as a primary part and 
the initial part of that recommendation.
    Senator Clinton. But a woman who is a potential recipient 
of a mammogram really has no independent way of determining the 
efficacy or the quality of the mammogram; so if I am asked by a 
constituent after this hearing what did Dr. von Eschenbach say 
should be done, what is my short answer?
    Dr. von Eschenbach. Beginning at age 40, you ought to have 
a mammogram every 1 to 2 years.
    Senator Clinton. OK, great. I just want to be absolutely 
clear about that.
    As to the second issue with respect to the quality and the 
efficacy, we will be reauthorizing the Mammography Quality 
Standards Act, recertifying it, I think this year. Will you be 
able to provide us with specific suggestions as to any 
modifications of the Act that might be helpful to address this 
controversy and increase the quality standards? I think there 
has been some debate about whether or not the MQSA has really 
lived up to its promise. Can you offer any suggestions as to 
what we can do to modify it when we reauthorize the Act?
    Dr. von Eschenbach. At this point, I could not, Senator, 
but I would be happy to provide that to you in subsequent 
information and material that would give you the kind of 
documentation that you need for an intelligent recommendation 
from me.
    Senator Clinton. That would be very helpful, because one of 
the things which is happening in New York, and I assume it is 
happening elsewhere, even before the back and forth of the last 
month or so, is that many physicians' offices and freestanding 
mammography clinics were eliminating the service because the 
reimbursement was insufficient to pay for the physician time, 
the technician time, and the overhead costs.
    So we have many parts of my State where it is very 
difficult to access a mammogram, and what I am worried about is 
that in light of this controversy, we will see more and more 
insurance companies determining that they will no longer cover 
the cost of mammography, concluding that because it is somewhat 
in dispute as to its importance, it is no longer a covered 
service.
    So I am hoping that your very straightforward statement 
that it is still the recommendation of the National Cancer 
Institute that women, staring at the age of 40, have 
mammograms, will give us the ammunition we need to avoid 
further cutbacks in access and reimbursement, which I am very 
concerned about.
    So I join the other members of this panel in thanking you 
for your testimony, thank you for taking on such an important 
task, because certainly those of us who have been involved in 
this issue for some time--and I see my friend Fran Visco out 
there--know that we have to do even more to find ways of 
preventing and curing breast cancer and that mammography is a 
tool in that fight, but it is not the principal weapon that we 
need to utilize.
    So thank you very much for being here.
    Dr. von Eschenbach. Thank you, Senator. You said it far 
better than I did. Thank you.
    Senator Mikulski. Thank you very much, Dr. von Eschenbach. 
If you would like to hang around, we would really welcome you 
at the end, perhaps, if you have any concluding observations.
    Dr. von Eschenbach. Thank you, Senator.
    Senator Mikulski. I will say to my colleagues that we have 
two excellent panels, one that we will call up now, which 
includes Dr. Donald Berry and Dr. Harmon Eyre.
    Dr. Berry is from the PDQ, and Dr. Eyre is from the 
American Cancer Society. They will be followed by a panel that 
will include the National Breast Cancer Coalition, a clinician 
representing the American College of Obstetricians and 
Gynecologists, and also a physician representing the Komen 
Foundation.
    Dr. Berry is an international expert and is the chairman of 
biostatistics at the University of Texas. He is also a 
principal investigator on a project funded by the National 
Cancer Institute to assess the relative contribution of 
screening mammography, tamoxifen, and chemotherapy in terms of 
the drop in breast cancer.
    We invited Dr. Berry to come and speak as a member of the 
Physicians' Data Query Screening and Prevention Board, the PDQ, 
which has raised some yellow flashing lights about the efficacy 
of mammograms.
    Dr. Harmon Eyre has a career-long interest in cancer 
research. He comes to us with an academic career in medical 
oncology. He has degrees from Utah and Hopkins. He has been 
recognized by the American College of Surgeons. We really 
welcome him to present the views of the American Cancer 
Society.
    Dr. Berry, we would like you to kick the panel off and give 
us the perspective of the PDQ, and then we will turn to 
questions.

  STATEMENTS OF DR. DONALD A. BERRY, CHAIRMAN, DEPARTMENT OF 
   BIOSTATISTICS, M.D. ANDERSON CANCER CENTER, UNIVERSITY OF 
   TEXAS, HOUSTON, TX; AND DR. HARMON J. EYRE, CHIEF MEDICAL 
 OFFICER AND EXECUTIVE VICE PRESIDENT FOR RESEARCH AND MEDICAL 
        AFFAIRS, AMERICAN CANCER SOCIETY, WASHINGTON, DC

    Mr. Berry. Thank you very much, Senator, and good 
afternoon. Thank you for inviting me to this important hearing.
    Just a word about Dr. von Eschenbach. I will say some 
things that disagree with Dr. von Eschenbach. I had the 
pleasure of serving with him on the faculty at M.D. Anderson 
for 2 years, and as a result of that have come to respect his 
opinion, his clinical abilities, and his person, and there is 
no one in medicine whose opinion I respect more than his.
    I serve on the PDQ Screening and Prevention Board. We 
discuss published literature and decide how to modify our 
website accordingly. This website is used by physicians and the 
lab public, so with respect to Senator Clinton's question, the 
women in her State can long onto the PDQ website and get 
information about screening benefits and risks.
    We assign levels of evidence to our statement. We are 
independent of the NCI. We are not advisory to the NCI. We do 
not establish guidelines. We do not make official 
recommendations.
    At a recent PDQ meeting, we discussed as a matter of course 
this paper that has been mentioned and referred to by Senator 
Mikulski and others by Olsen and Gotzsche that critiqued the 
randomized trials of screening mammography. We agreed with some 
of the criticisms but not with all. Our current statement 
indicates that the benefits of screening are uncertain, and 
based in part on this study, the plan is to modify the 
statement to add that the existence of a benefit is itself 
uncertain.
    The deficiencies with which we agreed are discussed in 
detail in my written report, which I ask to be included as part 
of the record. In each case, there was evidence of a bias 
favoring screening, but not all trials were subject to these 
biases.
    Briefly, first, women with pre-existing breast cancer were 
preferentially excluded from the screening group. Second, 
attribution of cause of death was not blinded. Third, in three 
of the Swedish trials, the timing of the control mammogram 
slipped, increasing the time to country breast cancer in the 
control groups. This is a technicality which we can get into if 
you would like, but it is an important bias. And fourth and 
finally, there have been no independent audits of the Swedish 
trials. In contrast, the Canadian trial which showed no 
screening benefit has been thoroughly audited.
    In my report, I explain how people can differ in their 
evaluation of evidence toward screening. At least 90 percent of 
what we know in medicine is the result of clinical observation, 
with the rest derived from randomized control trials. 
Experience is a great teacher, but when inferring the benefits 
of screening, clinical observation is flawed.
    Women with breast cancer detected mammographically have 
extremely good prognoses--extremely good prognoses--in 
comparison with those having cancers detected in any other way. 
But this does not mean that screening reduces mortality in 
itself. I explain why this is so in my report, and I discuss 
the associated biases. Hence the need for randomized trials.
    How impressive are the results of the trials? Suppose we 
ignore the Canadian trial which showed no screening benefit and 
take the results of the Swedish trials at face value. The most 
recent data from Sweden show a 21 percent reduction in breast 
cancer mortality. This is a paper that has been accepted to 
appear and is currently under embargo by the journal, so I 
cannot be too specific about it, but the 21 percent figure 
appeared in the press, and this is a lowering of the 30 percent 
figure which occurred earlier, and it applies to all ages; 
there is no distinction between less than 50 and greater than 
50.
    This is a relative risk reduction. One way to convert it 
into a more meaningful absolute measure of risk is to ask the 
corresponding increase in life expectancy. Out to 18 years of 
follow-up in the Swedish trials, this increase is about 4 days 
per women screened. In contrast, quitting smoking adds years to 
life expectancy.
    What should we tell women? The answer is the truth. The 
benefits of screening are uncertain, and women should know 
this; they should be informed of the possible benefits and 
risks along with the associated uncertainties and decide about 
screening for themselves. I discuss the risks of screening in 
my report, and I hope you ask me about that.
    Where do we go from here? We cannot do another randomized 
trial in this country--I completely agree with Dr. von 
Eschenbach--but there are several steps that we can take, and 
there are developments being pursued. One is that we should 
provide women with aids so they can make informed decisions 
about screening. Second, the Swedish trial should be 
independently audited.
    Third, there is an NCI-sponsored program called CISNET that 
addresses the question that Dr. von Eschenbach put up on the 
board regarding the decrease in breast cancer mortality, trying 
to apportion the relative contributions of screening 
mammography, hormonal therapy, and advances in chemotherapy.
    The fourth is the most promising of all. We know little 
about the biology of the disease, as Dr. von Eschenbach 
indicated, but we are learning. Cancers may manifest their 
metastatic potential when they are tiny, say, when they total 
only a few million cells, or they may start sloughing off their 
tumor cells for traveling through the rest of the body when 
they have become large enough to be detected mammographically. 
Screening would be effective in the second case, but not the 
first. We are learning fast about the biology of the disease, 
and soon will be able to decide which.
    I thank you for the opportunity to discuss this very 
important issue in women's health, a topic to which I have 
dedicated and will continue to dedicate my career. I am happy 
to answer questions.
    Senator Mikulski. Thank you very much, Dr. Berry.
    [The prepared statement of Mr. Berry follows:]
                   Prepared Statement of Donald Berry
      evaluating the evidence of benefit for screening mammography
    I serve on the PDQ (Physicians' Data Query) Screening and 
Prevention Editorial Board. We write statements for the NCI Website 
http://www.cancer.gov/cancer__information/ regarding screening for 
cancer and preventing cancer. However, we are independent of the NCI. 
Our statements are intended for and are accessible by physicians and 
the general public. We meet approximately six times per year to discuss 
recently published literature and on the basis of the available 
information we decide whether and how to modify our Website statements. 
We assign levels of evidence to our statements. Contrary to reports in 
the press, we are not advisory to the NCI, we do not establish 
guidelines, and we do not make official recommendations.
    I will give my understanding of the discussions and intentions of 
the PDQ Board. However, I have not been elected to be a spokesperson 
for the Board and so I do not have the right to speak for other members 
of the Board.
    My introduction to today's topic was my appointment five years ago 
to an NIH Consensus Development Conference Panel on Breast Cancer 
Screening for Women Ages 40-49. 1 had no ax to grind then and I have 
none now. My life is dedicated to understanding and fighting cancer--
breast cancer in particular. I am intimately involved in the prevention 
and treatment of this horrible disease. Nothing would please me more--
professionally and personally--than to have a tool that eliminates 
breast cancer or that turns it from a disease that kills into one that 
is chronic but can be controlled.
                         the randomized trials
    At the January 2002 PDQ Board meeting we considered an article 
authored by Drs. Ole Olsen and Peter Gotzsche of the Nordic Cochrane 
Collaborative and that appeared in The Lancet in October 2001. This 
article critiqued the randomized trials that have been conducted to 
evaluate the benefits of screening mammography and cited a number of 
deficiencies and flaws. Many of these were known previously and there 
was little original information in the review. However, it served to 
put the trials' deficiencies into perspective and led us to re-evaluate 
the credibility of the trials. We decided to revise our breast cancer 
screening statement and to refer to the Olsen-Gotzsche article. The 
plan is to discuss and possibly finalize the revision at our meeting in 
March. The current version of the statement indicates that the 
estimates of the benefits of screening are uncertain. Therefore, in a 
sense the revision will be minor. However, we plan to indicate that the 
existence of benefit is itself uncertain.
    Olsen and Gotzsche reviewed the seven randomized trials. One was 
conducted in Canada, one in New York, one in Edinburgh, Scotland and 
the other four in Sweden. The PDQ panel discounted some of the 
deficiencies pointed out by Olsen and Gotzsche but we agreed with 
others. In the first category, most of us (1) felt that their focus on 
all-cause mortality (rather than breast-cancer specific mortality) was 
too strong, (2) that imbalances in randomization were not a major 
concern (except in Edinburgh) and (3) regard the use of mammograms in 
the control groups (to coincide with the end of the screening period) 
of three of the Swedish trials to be a reasonable design strategy. From 
our perspective the trials had four types of major deficiencies. They 
applied to some but not all of the trials. The first three are 
potential sources of bias favoring the screening group and in each case 
there is some evidence of actual bias in the trials.
    (1) Women with pre-existing breast cancer were preferentially 
excluded from the screening group. The problem was most severe in the 
New York trial in which 853 women in the screened group and 336 in the 
control group were excluded because they had breast cancer at the time 
of randomization. Excluding women with breast cancer is not 
unreasonable, but the numbers excluded in the two groups would be about 
the same had there been no bias. If these women had been included and 
only 9 percent of the differential of 517 women died of their disease, 
the breast cancer mortality rate would have been higher in the screened 
group than in the control group.
    (2) Attribution of cause of death was made with knowledge of 
whether the woman was in the screened group. Blinding assessment of 
cause of death to assigned intervention is fundamental in good clinical 
trial practice. For example, an assessor might be more likely to 
attribute a death to lung cancer if the woman's cancer was detected 
through screening and to metastatic breast cancer if the woman had been 
in the control group. There is evidence that this bias was real. The 
numbers of deaths have changed in unusual ways from one report of the 
trial results to the next: The number of breast cancer deaths in the 
control group always increases over time but it sometimes decreases in 
the screened group.
    (3) In three of the Swedish trials women in the control group were 
supposed to have a mammogram, which was scheduled at the time of the 
last mammogram in the screened group. Then, deaths due to breast cancer 
in the control group would be counted only if they were diagnosed at or 
before this mammogram and in the screened group if they were diagnosed 
at or before the last mammogram. This design is reasonable. But the 
scheduled control mammogram slipped in all three trials, allowing for 
more time to detect cancers in the control group. The slippage was by 
as much as 18 months. As a consequence, the control group in the 
Goteborg trial had 21% more breast cancers detected than did the 
screened group. Such an observation seems impossible (in an unbiased 
design) because mammography is very good at finding breast cancers.
    (4) No independent audit of trial results. Having an independent 
audit is a generally accepted in medical research and it is essential 
for a trial to be credible. For example, the FDA routinely audits 
clinical trials that provide the basis for an experimental drug's 
safety and efficacy. None of the Swedish investigators have opened 
their results to external inspection (but some have recently indicated 
their willingness to do so).
    The Canadian trial was subject to none of these biases. It has been 
extensively audited and its data are openly available for external 
examination. Both parts of the Canadian trial (one admitted women in 
their 40s and the other admitted women in their 50s) found a higher 
breast cancer mortality rate in the screened group, although the 
increase was not statistically significant. The other trials fell prey 
to one or more of the biases, although it is not known whether there 
were biases in the first part of the Malmo trial.
       how can people differ so in their evaluation of evidence?
    Physicians learn by experience. At least 90 percent of what is 
known in medicine today is the result of clinical observation, with the 
remaining knowledge deriving from randomized clinical trials. 
Experience is a great teacher. But when it comes to inferring the 
benefits of screening, clinical observation is fundamentally subject to 
flawed interpretation.
    Women with breast cancer detected mammographically have extremely 
good prognoses in comparison with those having cancers detected in any 
other way. Mammographically detected tumors are smaller and are less 
likely to have spread to the axillary lymph nodes. Since women whose 
breast cancers were found by a mammogram do so much better, there is a 
tendency to attribute the benefit to mammography. Unfortunately, this 
logic is wrong. The fallacious aspect is not simply a nuance--it is a 
mistake that gives rise to profound misconceptions. And it is a logical 
lapse to which doctors and patients alike can fall prey.
    Suppose temporarily that screening mammography has no survival 
benefit. Clinicians would still see precisely what they do see. 
Consider a 50-year-old woman who has breast cancer and who is destined 
to die of her disease at age 60. However, she does not yet know that 
she has breast cancer. It would be found on a mammogram if she were to 
have one, and she would live for ten years with breast cancer. But 
without a mammogram it would show up clinically only when its symptoms 
become apparent, say at age 55. So without a mammogram she lives for 
only five years after her cancer is discovered. The discrepancy between 
ten years and five years results from what is called lead-time bias. It 
means that women whose cancers detected by mammography live longer than 
do those detected otherwise, and this is true even if screening has no 
true benefit.
    There is another kind of bias--called length bias--that is even 
more important in magnitude, but it is not as easy to understand. It is 
related to the fact that breast cancer is a heterogeneous disease. 
Again, assume temporarily that screening has no survival benefit. We 
understand some of the factors that give rise to this heterogeneity, 
but not all of them. Some cancers grow rapidly and others take a more 
indolent course. Suppose just for the sake of discussion that there are 
two kinds of cancers: half grow fast and the other half grow slowly. We 
cannot determine which is which and so we treat them similarly. Suppose 
that after their cancer is detected via mammography, patients having 
the first type live an average of five years and patients with the 
second type live an average of 35 years (not counting causes of death 
other than breast cancer). So the average survival for women whose 
cancers are detected by mammograms is about 20 years. In the absence of 
mammography the first type of cancer might show symptoms with only 
three more years to live (a lead-time of two years). Some portion--say 
one half--of the women who harbor the slowly growing tumors will die of 
other causes before it is discovered. The other half of these women 
will discover them with 24 more years to live, say, a lead-time of 11 
years. There will be 25 percent fewer breast cancers in the non-
mammography group. Two-thirds will live an average of three years and 
one-third will live an average of about 24 years, for an overall 
average of ten years. So women diagnosed with mammography live about 
ten years longer than those detected otherwise. This enormous 
difference is pure artifact since we assumed that screening had no 
benefit.
    The above assumptions were simplified to make a point. No one 
thinks that there are only two kinds of breast cancer. But everyone 
recognizes that the disease is heterogeneous. Length bias and lead-time 
bias are present regardless of the form of heterogeneity. Together they 
account for enormous differences in apparent survival, as measured from 
the date of diagnosis, between screened and unscreened cancer patients. 
These differences are so large that they are detectable by physicians 
in their everyday practices. No wonder physicians are persuaded of 
screening's benefits. But the observed benefits may be completely 
spurious. In other words, apparent survival from diagnosis may be 
longer, but life expectancy may not change at all. Hence the need for 
randomized trials.
                    relative risk vs. absolute risk
    If there is a benefit of screening then the benefit is modest. To 
see this, ignore the criticisms of the trials and take their results at 
face value. The benefits evinced vary considerably from one trial to 
the next. Outside of the Canadian trial (which showed no benefit), the 
highest quality results are from the Swedish trials. The most recent 
results (out to 18 years) of the Swedish trials show a reduction in 
breast cancer mortality of 21% (over all ages) in favor of screening. 
The value 21% is a relative risk reduction, which is convenient as a 
statistical measure of benefit. But relative risk is difficult to 
interpret clinically. One measure of absolute risk is to convert the 
21% into expected life gained per woman screened. In the first 18 years 
following initiation of screening in the Swedish trials the average 
gain is about 4 days. (In contrast, quitting smoking adds years to 
one's expected lifetime.) Of course, only those women who are 
eventually diagnosed with breast cancer share in any benefit. Suppose 
10% of the women get breast cancer eventually. Then each woman with 
cancer gains an average of about 40 days. How this is apportioned among 
the women diagnosed with cancer is not clear. From the trial results it 
is impossible to distinguish whether (i) each breast cancer patient 
gains exactly 40 days, (ii) fewer than one percent of patients gain 18 
years or more and the rest gain nothing, or (iii) something between 
these two extremes. Put another way, it is not possible to know whether 
a small proportion of lives are saved by screening or a large number of 
women have their lives extended by a small amount, or some combination 
of the two.
                       what should we tell women?
    The short answer is ``The truth.'' The benefits of screening are 
uncertain and women should be told this. They may be confused. 
Confusion is a legitimate state of knowledge, one that may be 
appropriate in this case. It is a mistake and it is patronizing to 
women to pretend that we know something we do not. Women have a right 
to hear about the risks of screening and about the uncertainties 
regarding the benefits of screening. They should hear all points of 
view and then decide for themselves. Making this decision will not be 
easy for some women. We should provide them with decision aids that 
will inform them of what is known and help them weigh the benefits and 
risks.
    The risks of screening may seem minor but they are important 
nonetheless, and they are common. From four percent to ten percent of 
women screened are found to have an abnormal result. The ensuing 
recommendations range from a follow-up mammogram to having a biopsy. 
Eighty to 95 percent of the abnormalities turn out to be benign. 
Obviously, not having cancer is good news, but an estimated 28 million 
women have mammograms each year, and so a million or more go through 
the anxious experience of an abnormal test until the final result is 
known. After ten mammograms the cumulative risk of a false positive 
result is about 50 percent and about 1 in 6 have biopsies that turn out 
to be negative. In addition, we know that screening misses about 15 to 
25 percent of breast cancers.
    Another potential consequence is overdiagnosis. Some breast cancers 
that may never have progressed become symptomatic during a patient's 
lifetime. We don't know which of these cancers will progress and so 
essentially all women with screening-detected breast cancer are treated 
surgically, with or without radiation. This may result in unnecessary 
surgery for some women. Of course, even this serious consequence may be 
acceptable if the test is saving the lives of other women.
    A problem with setting guidelines such as those we have now is that 
it conveys the message to physicians that screening is an imperative 
health measure. A woman who decides that the risks outweigh the 
benefits should not be made to feel that her decision is somehow 
irrational. A 58-year-old woman from New Jersey sent me the following 
lament: ``Sadly, in my experience anyway, I have found it impossible to 
have a rational conversation with a physician, where my concerns are 
respected on the topic of mammograms, as the NYTimes article says a 
patient should have. Doctors get belligerent and almost hostile if I 
say I have reservations about getting a yearly mammogram. The upshot is 
that I don't feel I have a good relationship with a physician, and that 
is not good. A good scientist is not afraid to express uncertainty on a 
topic or to discuss a topic openly. I'm afraid the practicing 
physicians who I have come across do not have that scientific mind-
set.''
                         where to go from here?
    It is not possible to do another randomized trial, at least not in 
the United States. Women want either to be screened regularly or not. 
Few would let a coin toss make their decision. However, there are 
developments that may help elucidate the issue, and steps that we can 
take.
    (1) Provide women with decision aids in which they are informed of 
the benefits and risks, including uncertainties, and helped to weigh 
them in making a decision.
    (2) Audit of the Swedish trials. A positive consequence of the 
PDQ's position and the ensuing discussion in the press was reported by 
John Crewdson in the Chicago Tribune of January 31, 2002: Several of 
the Swedish investigators ``announced last week that they would release 
their detailed data, including patient files, to researchers at the 
U.S. National Cancer Institute or another international body.'' 
(Hopefully, the recently announced NCI guidelines will not lead to the 
Swedes withdrawing this offer.) If an audit of these trials examines 
the biases and confirms the recently announced 21% reduction in breast 
cancer mortality then I for one will agree that screening has a 
benefit.
    (3) Cancer Intervention and Surveillance Network (CISNET). This is 
an NCI-sponsored program that considers a variety of cancers. I am one 
of seven Principal Investigators considering breast cancer. Breast 
cancer mortality in the United States has decreased by nearly 15% over 
the last decade. This coincides with the wide scale introduction of 
screening mammography. It also coincides with the dramatic upsurge in 
the use of tamoxifen and improvements in chemotherapy. We use 
statistical modeling to conclude how much screening mammography, 
hormonal therapy and chemotherapy have contributed to this decrease. Of 
special interest is the possibility of synergism between screening and 
treatment. For example, it may be that treatment with tamoxifen and 
chemotherapy has more benefit when a tumor is discovered by a mammogram 
at an earlier stage. We use annual data concerning who got screened, 
who used tamoxifen, etc. An advantage of this approach is that it 
applies to mammography actually used in practice in the late 1980s and 
into the 1990s, which may have been better than that used in the 
randomized trials. Another advantage is that we assess effectiveness in 
the context of actual clinical practice rather than in the possibly 
artificial world of clinical trials.
    (4) The third development is the most promising of all. Our 
understanding of the biology of breast cancer has increased greatly in 
recent years, but we still know relatively little. Breast cancer would 
not be fatal if it were to stay in the breast. Its lethality stems from 
its penchant for traveling to and setting up shop in other places in 
the body, such as in bone, the lungs, liver and brain. The question is, 
When does it do these things? Perhaps cancers manifest their metastatic 
potential (or not) when they are tiny, say when they total only a 
million or so cells. If so then they will have dispatched their 
malevolent messengers from the breast to the rest of the body before 
even the best mammography can detect their presence. Or it may be that 
they start sloughing off tumor cells only when they become large enough 
to have been detected and removed. We know little about such matters. 
And we know little about the relationship between the biological 
characteristics of tumors and how to treat them. These issues are being 
addressed by researchers around the world. Research progress will help 
us better understand the relationships between biological markers, 
early detection and treatment. Especially exciting are the genomics and 
bioinformatics revolutions. These are in their infancies and are well 
funded, but they deserve all the attention they have received.
    Thank you for the opportunity to discuss this extremely important 
issue in women's health, a topic to which I have and will continue to 
dedicate my career. I would be happy to answer questions or provide 
further details.

    Senator Mikulski. Dr. Eyre?
    Dr. Eyre. Good afternoon, Madam Chairwoman and 
distinguished members.
    As chief medical officer at the American Cancer Society, I 
am honored to be here today and want to thank you for the 
opportunity to testify about the strong science supporting the 
value of mammography in saving lives.
    The American Cancer Society is the largest community-based 
health organization dedicated to preventing cancer, saving 
lives from cancer, and diminishing suffering from cancer.
    We have established very ambitious goals for the year 2015 
to reduce the incidence and death rates of cancer as well as 
improve the quality of life of cancer patients. In order to do 
that, cancer prevention and early detection is a critical 
aspect of this strategy.
    You have heard from Dr. von Eschenbach about the magnitude 
of the breast cancer problem, but one fact he did not give you 
which I think is astounding is that a woman who dies of breast 
cancer in America loses 19 years of life due to premature 
death, as judged by average life expectancy. As a medical 
oncologist and cancer specialist, I have personally taken care 
of over 1,000 patients with breast cancer and witnessed the 
suffering that occurs to patients and their families from 
breast cancer, and I believe that we are making vast progress 
in this country, saving thousands of lives from breast cancer, 
and I hope to not see that reversed.
    We too would add our encouragement behind the U.S. 
Preventive Services Task Force's recent affirmation of 
mammography and believe that it adds to the scientific evidence 
behind it. The scientific evidence supporting mammography in 
reducing breast cancer death rates is solid, and I would like 
to share just a few comments about the Society's position on 
this.
    Over 100 years ago, it was hypothesized by a French 
physician that breast cancer began as a single focus, gradually 
began to spread, went through the lymphatic channels into the 
vascular channels, resulting in the death of the person. This 
concept has been verified and gives rise to the notion that if 
you can find it early enough, surgical removal of the cancer 
results in cure.
    It was not until the 1950's, however, that we began to find 
mammography able to detect early breast cancer, and this gave 
rise in the 1960's, actually, to the HIP study in New York City 
which was the first large-scale randomized trial, with 62,000 
women randomized to mammography and clinical breast exam versus 
usual care. The result of that study after follow-up was a 30 
percent reduction in death rate in breast cancers in the study 
group compared to the control group.
    Before moving on, I would like to discuss with a little bit 
of evidence the data on size and stage of cancer. If you find 
early disease--no lymph node involvement, no disseminated 
disease--5-year survival of breast cancer in America is 97 
percent. In contrast, if you find breast cancer when it has 
already demonstrated spread, 79 percent of those women will die 
in that first 5 years. Our goal is survival, and the scientific 
evidence has repeatedly demonstrated that screening can help 
achieve this goal.
    Following the HIP study, the American Cancer Society and 
the National Cancer Institute launched a major nationwide 
demonstration project, the BCDDP, in which at 10 centers, 
280,000 women were screened from 1973 to 1980, and comparing 
the results of those individuals to the results of the 
population revealed a substantial reduction in mortality.
    Subsequent to those trials, there have been studies in 
Great Britain, in Sweden, and in Canada. Almost all of those 
studies except the Canadian studies have demonstrated a 
statistically significant reduction in mortality. The Cochrane 
group, as you know, has recently criticized these studies. We 
find their analysis flawed. We do not agree with the fact that 
those studies had substantial imbalances within them, and in 
fact the Cornell group pointed out in the Malmo study that 
Senator Harkin referred to that if you had just followed the 
people longer, there was a significant reduction in mortality, 
and the Cochrane group did not even acknowledge that second 
report.
    We believe that mammography is not a perfect test; it has 
flaws. It is an interim effort to help control breast cancer, 
and as we progress--and we applaud Dr. von Eschenbach's 
scientific studies, and we are funding scientific studies into 
finding answers as to how to present cancer, how to block it 
from occurring, and if it occurs, how to cure it--it will only 
be then that we will get the final control. But in the 
meantime, mammography is of value in reducing the death rate 
from breast cancer, and the American Cancer Society applauds 
and continues to support this effort with information to 
patients, to women, and with the recommendation that women 40 
and over should have annual mammograms.
    Thank you.
    [The prepared statement of Dr. Eyre follows:]
               Prepared Statement of Harmon J. Eyre, M.D.
    Good afternoon, Madam Chairwoman, Mr. Chairman, Senator Frist, 
Senator Specter, and distinguished members of both Committees. I am Dr. 
Harmon Eyre, Chief Medical Officer and National Vice President for 
Research and Medical Affairs of the American Cancer Society. I am 
honored to be here today, and I want to thank you on behalf of the more 
that 28 million volunteers and supporters of the Society for the 
opportunity to testify about the strong scientific evidence supporting 
the value of mammography in saving lives from breast cancer. The 
American Cancer Society commends you for conducting this very timely 
and important hearing.
    I respectfully asked that my comments be submitted for the record.
    The American Cancer Society is the largest nationwide community-
based voluntary health organization dedicated to eliminating cancer as 
a major health problem by preventing cancer, saving lives and 
diminishing suffering from cancer through research, education, advocacy 
and service. We have set ambitious goals for the year 2015 to reduce 
the number of people dying from and being diagnosed with breast and 
other types of cancer, and to significantly improve the quality of life 
for all cancer patients, survivors, and their families. While we 
believe that national achievement of these goals is possible, increased 
awareness and utilization of cancer prevention and early detection 
tools is critical to our success.
    Madam Chairwoman and Mr. Chairman, before setting out to explain 
the American Cancer Society's view on the benefits of mammography, I 
would like to take a moment to call attention to the terrible impact 
that breast cancer is having on women in this country. This year, 
203,500 new invasive cases of breast cancer will be diagnosed, and an 
estimated 40,000 women will die of the disease. On average, a woman 
dying of breast cancer loses approximately 19 years of life she might 
otherwise have had. The human face on those statistics translates into 
families watching a loved one struggle with advanced, unsuccessfully 
treated disease, and a family and community that ultimately are left to 
mourn her loss. As a physician and medical oncologist, I have treated 
thousands of breast cancer patients in my career and observed first 
hand the heartbreak this disease visits on families and loved ones. 
Over the years, I have also witnessed the progress we have made, so 
that fewer women are dying from breast cancer. I do not wish to see our 
country lose the ground we have gained.
    To this end, we are hopeful that the recent announcement of the 
U.S. Preventive Services Task Force's update of their breast cancer 
screening guidelines and their endorsement of mammography for women 
ages 40-69, will add to the weight of the wide-scale rejection of the 
recent mistaken notion that mammography is valueless.
    Madam Chairwoman, Mr. Chairman, and members of both committees, the 
scientific evidence supporting the value of mammography in effectively 
reducing deaths from breast cancer is solid, and I appreciate having 
the opportunity today to share with you the Society's view on this 
important subject.
            the origins of early detection in breast cancer
    The importance of detecting localized breast cancer is well 
established. It was first recognized in the mid-18th century by a 
French physician who proposed that breast cancer originated as a 
localized disease that subsequently spread through lymphatic channels 
to the general circulation. This key concept established the idea that 
surgery, if performed early, offered the potential to cure breast 
cancer. Effective means of early detection eluded us, however, until 
the early 20th century when it was first demonstrated that breast 
disease could be detected with x-rays, allowing for diagnosis of breast 
cancer even before symptoms, such as lumps, could be detected by a 
woman or her physician.
    As you well know, the path toward turning a promising idea into a 
practical solution can be a time consuming journey in the scientific 
world, because of the high standards of scientific evidence that are 
required. Promising work in breast imaging continued through the first 
half of the 20th century, eventually leading to a turning point in the 
early 1960s when Dr. Philp Strax, a radiologist in one of the Health 
Insurance Plan of Greater New York medical groups, proposed a large-
scale study to evaluate the potential of mammography and clinical 
breast examination to reduce deaths from breast cancer. Professor Sam 
Shapiro, Director of Research and Statistics at the Health Insurance 
Plan, and Dr. Louis Venet, a surgeon with experience in clinical breast 
examination screening programs, later joined him as co-investigators. 
This study became the Health Insurance Plan of Greater New York 
Project, historically known as the HIP Study, and was initiated in 
December 1963. It was the first randomized, controlled trial to 
evaluate the efficacy of breast cancer screening with clinical breast 
examination (CBE) and mammography. Approximately 62,000 women aged 40-
64 were randomly assigned to two groups: the study group was offered 
annual clinical breast examination and two-view mammography for four 
years, and the control group received usual care.
    The fact that this study was a randomized controlled trial is 
important because, with respect to cancer screening, it is critical to 
know whether the actual act of screening is the factor making the 
difference in saving women's lives. The ideal study would be one in 
which you had two identical groups of people, with the only difference 
between them being whether they were screened. Obviously, a study like 
that is impossible. Therefore, the next best thing is to randomly 
assign a large group of individuals to either the group that is offered 
screening or the group that receives usual care. If our randomization 
has succeeded, and the study is well organized to maintain the 
integrity of equality between the study group and the control group, 
then we come very close to the theoretical ideal of two identical 
groups. Randomization of the women in the study controls for factors we 
know about and factors we don't know about that could bias our 
findings. It helps us demonstrate whether or not screening, and not 
some other factor, is the reason death rates are reduced.
    The HIP study was a dramatic turning point. It offered hope for the 
first time that through intervention we could reduce the number of 
women who died from breast cancer. The randomized HIP study 
demonstrated that there were approximately 30% fewer breast cancer 
deaths in the study group compared with the control group. Without 
question, the results of the HIP study ushered in a new era in breast 
cancer control, one in which there would be increasing emphasis on 
detecting and treating breast cancer before the onset of symptoms. 
However, scientists are rarely willing to recommend wholesale change in 
health policy based on one study.
                    the logic behind early detection
    Before I talk about the next series of studies, I want to quickly 
discuss the logic behind early detection and the relationship to the 
underlying biology of breast cancer. Breast cancer is a progressive and 
systemic disease, in which our ability to treat and cure a small tumor 
is much greater than our ability to treat and cure a larger tumor. 
Treatment is easier and the outcomes are better, when the cancer is 
caught before there is lymph node involvement and before the cancer has 
metastasized, or spread, to distant organs. There is no more consistent 
and straightforward measure of a breast cancer patient's prognosis than 
the size of the tumor. A few statistics to put this in perspective: 
When breast cancer is still localized--meaning that it has not spread 
to other organs--97 percent of patients survive for five years or more. 
Once the disease has spread to other organs, however, prognosis is 
bleak, with 79 percent of patients dying within five years. Our goal is 
survival--and scientific evidence demonstrates that screening can help 
us achieve the goal of lives saved. Indeed, the important role 
screening plays in reducing breast cancer deaths has been demonstrated 
repeatedly.
  promising concept to promising solution: the importance of routine 
                        breast cancer screening
    As I mentioned, the HIP study was not enough on its own to 
recommend screening to the general population. Before recommending 
screening to the general population, we would have to not only know 
that screening works, but that it was possible to implement an 
effective screening program in the community. The results of the 
landmark HIP study led the American Cancer Society and the National 
Cancer Institute to collaborate on a larger project to determine the 
practicality of bringing mammography screening to women at the 
community level. This project, known as the Breast Cancer Detection 
Demonstration Project, or BCDDP, screened over 280,000 women at 29 
centers between 1973 and 1980. Participation rates were high over the 
course of the study and final analysis underscored the importance of 
mammography screening--nearly half of all breast cancers in this study 
were found by mammography alone.
    Furthermore, among study participants, breast cancers were 
diagnosed at more favorable, early stages when compared with breast 
cancer cases among women nationwide during the same period. Most 
importantly, overall long-term survival has been much better among 
participants in the screening study. The bottom line is that, based on 
these two studies, we now had enough scientific evidence to say that 
mammography was an effective tool to detect breast cancer early, and 
breast cancer deaths would be reduced if we detected the disease before 
it had spread. Mammography was a tool that could make a difference.
    Thanks to the groundbreaking results of the BCDDP and the HIP 
study, the Society determined that there was sufficient evidence to 
promote routine breast cancer screening in the U.S. as a public health 
initiative in 1980. As the largest national health organization devoted 
to reducing cancer incidence and deaths, the American Cancer Society is 
well recognized as a primary resource for cancer screening guidelines. 
Our screening guidelines are established through a rigorous scientific 
review process and are re-evaluated at least every five years. We have 
reviewed the scientific evidence relating to mammography repeatedly 
since 1980, and we have continuously concluded that while improvements 
in technology are certainly welcome, mammography remains the best tool 
we currently have to detect breast cancer early. In fact, as the 
Institute of Medicine recently concluded, mammography presently is the 
gold standard by which breast cancer is detected early.
    As I mentioned, evaluation of mammography has continued. Between 
1976 and 1982, six additional randomized controlled trials were 
initiated in Edinburgh, Sweden, and in Canada. While there are 
differences in the results, all of these studies (with the exception of 
the Canadian studies) show a benefit from breast cancer screening with 
mammography, both with and without clinical breast examination. In 
fact, the trials show a statistically significant reduction in breast 
cancer death by about 25-30 percent for women aged 40 and older and 
similar benefits for women in their forties compared with women aged 50 
and older.
    The accumulation of evidence from randomized trials over the years 
has strengthened the science behind breast cancer screening. In fact, 
one remarkable observation from the trials is that in the group offered 
screening, the observed reductions in the mortality rate in each trial 
are consistent with reductions in the rate of advanced breast cancer 
when compared with the control group. Put simply, the studies showed 
that detecting breast cancers early increases the chances of survival.
    It is important to note that trial results derive from controlled 
environments. It is also necessary to demonstrate whether true benefits 
are being achieved under real-life circumstances. In Sweden where 
screening is a national health priority, those women receiving regular 
screening have been shown to reduce their risk of dying from breast 
cancer by over 40 percent compared with women who do not get regular 
screening--a fact that should not be ignored.
   revisiting complex questions: reports from cornell university and 
                                cochrane
    Madam Chairwoman and Mr. Chairman, as you know, in spite of the 
overwhelming evidence, mammography has not been without its detractors. 
Recently, two of these detractors have been able to gain widespread 
media attention and cause great confusion among the public about the 
value of mammography. I am speaking of course about the Cochrane Review 
on Screening for Breast Cancer as published in the Lancet. In my view, 
this current confusion is a regrettable development that is harmful to 
women. Given the weight of evidence from the trials and the reductions 
in breast cancer death rates observed in real life instances, the 
conclusions of the Cochrane Review are quite frustrating to many in the 
scientific community. Indeed, the Cochrane conclusions are at odds with 
the most fundamental understanding of breast cancer as a progressive 
disease. Moreover, these conclusions run contrary to decades of 
supporting scientific evidence from the individual trials, meta-
analyses, observational studies and case series, national trends, and 
confirmatory, independent expert reviews conducted by medical and 
scientific groups in North American and Europe.
    As you are probably aware, the Cochrane report rejected five of the 
seven major mammography trials as flawed. The researchers then claimed 
that the two remaining trials showed that mammography was not 
beneficial. Inexplicably, one of the reports they selected was an early 
report of the Malmo study. The early report was made before there had 
been sufficient time for follow up and therefore did not show a 
difference in breast cancer deaths between the study group and control 
group when all deaths in each group were compared. For some unknown 
reason, the Cochrane review ignored a second later report of this study 
that had allowed sufficient time for follow up. This later report did 
indeed show that mammography was beneficial. In fact, it showed that 
there were 19% fewer deaths in the group offered screening.
    Because most breast cancer deaths do not occur rapidly after 
diagnosis, experts in the evaluation of screening have known for years 
that a lengthy period of follow up in a screening study is necessary to 
observe a lower mortality rate if there is one. In fact, this very 
point was strongly made in a report in the Lancet only a few weeks ago 
by investigators from Cornell University. The Cornell investigators 
demonstrated that once a sufficient amount of follow up was allowed, 
even the first Malmo study shows a clear reduction in breast cancer 
deaths. In other words, the Cochrane analysis used incomplete data, 
making their conclusions suspect.
    Knowing that the results of a scientific study can have a great 
impact on many aspects of health care and health policy, standards for 
conducting these types of studies are set high and are adhered to by 
most of the scientific community. Unfortunately, on close examination, 
it is evident that the Cochrane review does not adhere to some of these 
standards and is deeply flawed. Indeed, it appears that the review's 
investigators failed to perform a careful examination of the published 
literature--for example, missing the second Malmo report--and made 
arbitrary and inconsistent judgments about study quality. Moreover, the 
Cochrane analysis concluded that the only reliable endpoint for 
comparison was not death from breast cancer, but death from all causes.
    Using death from all causes as the means for evaluating mammography 
effectiveness is far-fetched in the extreme. The trials were designed 
to demonstrate a difference in breast cancer deaths--not deaths from 
all causes. To demonstrate a difference in deaths from all causes, an 
enormous number of people would need to be enrolled in any trial. These 
trials were too small to individually demonstrate a difference in all 
cause mortality and were never intended to do so. Moreover, breast 
cancer screening cannot logically be expected to reduce deaths from hip 
fractures, diabetes, trauma, or other causes of death.
    Furthermore, the Cochrane analysis alleges that some of the trials 
should be ignored because of possible bias and error in determining the 
cause of death. This assertion is simply wrong, since the level of 
error, due to dishonesty or incompetence on the part of blinded and 
non-blinded expert panels, would have had to be entirely habitual to 
change the results so completely. All told, the claims made by the 
Cochrane review are based more on conjecture than an actual 
demonstration of errors.
    The authors of the Cochrane analysis are part of a group in the 
scientific community who hold that studies should look only at all-
cause mortality, not on mortality from breast cancer alone. This train 
of thought is quite misleading, because the goal of any preventive 
health program is not to prevent death, which will occur eventually, 
but to reduce our chances of dying prematurely Breast cancer screening 
makes sense for women between the ages of 40 and 70 because breast 
cancer is a leading cause of death in that age group--it offers women 
the chance to save those 19 years of life that I mentioned at the 
beginning of my remarks.
    This raises another point. Screening is an undertaking in which we 
test the many to find the few. No screening test is 100 percent 
accurate. In some cases, cancer will be missed during screening. In 
other cases, women will be told they need additional tests for 
abnormalities that ultimately turn out not be cancer. Providers must 
handle each step of the screening process with great sensitivity. 
Likewise, more education can be done to assure women that ``false 
positives'' are part of the pathway to a normal interpretation. A group 
of investigators at Dartmouth found that women are highly accepting of 
false positives as part of the process of saving lives from breast 
cancer. This does not mean we should not devote more attention to 
reducing the avoidable false positive rate, but it is important to note 
that many women understand the inevitability of false positives and 
accept them as part of the process of early detection.
    Another criticism of mammography is that it detects ductal 
carcinoma in situ, or DCIS, a non-invasive cancer. In the course of 
screening for invasive breast cancer, we will detect DCIS. Since not 
all DCIS will progress to invasive disease, screening has been 
criticized for over treating DCIS.
    Madam Chairwoman and Mr. Chairman, approximately a third of DCIS 
may progress to invasive disease and we do not know which will or will 
not progress. The notion that detection of DCIS should be avoided, or 
that screening should be postponed until DCIS progresses to invasive 
disease betrays a fundamental misunderstanding about the biology of 
breast cancer and the interplay between disease progression and early 
detection. The intent of breast cancer screening is the detection of 
small invasive cancers in order to give women an advantage in fighting 
their disease. The challenge today and in the future is tailoring the 
treatment of DCIS to ensure that it is treated appropriately and that a 
woman is not put through a greater treatment ordeal than is necessary--
but that's a treatment issue not a screening issue. The only option for 
avoiding the diagnosis of DCIS is not being screened for breast cancer, 
which would make no sense at all since the incidence rate of invasive 
breast cancer is many times greater than the chance of a diagnosis of 
DCIS.
    All told, in addition to numerous critiques of the Cochrane Review 
in published literature by well-known experts on screening, no national 
or professional body has found that this review's conclusions are 
convincing. As additional reviews are published, and as additional 
national groups reject the review's flawed interpretation of the data, 
it is our hope that policymakers and others will devote more attention 
toward setting the record straight. Mammography, while not a perfect 
tool, is currently the best tool we have to catch breast cancer early 
and to reduce deaths from the disease.
                               next steps
    Madam Chairwoman, Mr. Chairman, and members of the Committee, we 
have made incredible progress towards reducing deaths from breast 
cancer in North America and Europe. Here in the U.S., after nearly two 
decades of a public-private partnership in health promotion, a majority 
of women aged 40 and older are receiving mammograms. The efforts to 
improve the quality of mammography, and in particular the importance of 
the landmark Mammography Quality Standards Act of 1992, which the 
Chairwoman authored, have assured every woman in this country of higher 
quality breast imaging. These efforts have produced results. The death 
rate from breast cancer has declined by over 20% in the last decade. 
According to the American Cancer Society, progress in the U.S. in 
breast cancer screening, improved therapy, and increased awareness 
means that there will be many thousands fewer women who will be 
expected to die this year from breast cancer than would have died if 
mortality rates were the same today as they were in 1989. Furthermore, 
new technology, such as digital mammography, computer-aided detection, 
and potentially MRI hold the promise for even more successful breast 
imaging technology--but at this time, mammography is the best tool we 
have.
    The American Cancer Society will continue to provide information 
designed to inform women of the benefits and limitations of mammography 
screening. We are confident that, armed with information, women and 
their health care providers will continue to see mammography as the 
best current strategy to reduce death from this disease, and that those 
whose confidence was shaken by the recent media attention will regain 
their confidence as the authoritative and credible interpretation of 
the scientific data on mammography prevails. To this end, we urge women 
40 and older to continue to follow the advice of their physician and be 
screened for breast cancer annually.
    Madam Chairwoman, Mr. Chairman, and members of the Committee, thank 
you again for the opportunity to speak to you today.

    Senator Mikulski. Senator Harkin, you chair the 
appropriations committee on the other part of this joint 
hearing, so why don't you kick off the questioning of this 
panel?
    Senator Harkin. Thank you very much, Madam Chair.
    Dr. Berry, again, in layman's terms, let me try to propound 
this question. All things being equal, if a woman has the 
opportunity to have mammogram screening available to her after 
age 40--and she can obviously do a self-exam and have a 
physical every year--would it be your advice to her to skip the 
mammogram, assuming she can afford it, it is available and so 
on? Would you say just skip it, or would you advise her to have 
a mammogram as part of the toolbox that we talked about earlier 
of different things that we can do to try to detect breast 
cancer?
    Mr. Berry. I would not advise either way. I would discuss 
with the woman--as, for example, I have with my wife and 
daughters--what the benefits are, what the uncertainties are 
associated with those benefits, what the risks are--and the 
risks may be more important for one woman than for another 
women--and if that woman, including members of my family, 
decided to have a mammogram, I would support that to the 
utmost; if they decide not to, I would support that as well.
    Senator Harkin. Is it true--or, is it factual--that the 
earlier breast cancer is discovered, the higher the possibility 
will be--or probability will be--that a woman could 
successfully have that treated one way or the other--through 
surgical removal or whatever--and have a longer life span and a 
healthier quality of life than if that woman waited until the 
cancer had grown and metasticized?
    Is that a factual statement or not? Do you want me to 
repeat it?
    Mr. Berry. No, no. I think I understand the question. If a 
woman has cancer--if somebody says to you, ``I have cancer,'' 
and it was detected mammographically, that woman has incredibly 
good prognosis. If it is not detected mammographically she has 
poor prognosis. That does not mean that the mammogram did it.
    As Dr. von Eschenbach indicated, there are tumors that are 
relatively indolent that are found with mammogram that may not 
ever be found in the course of the woman's life. Autopsy 
studies have shown in the United Kingdom that women have as 
much as 35 percent invasive disease that never affected their 
health.
    There is a lead time bias. There is a lead time associated 
with mammography that if you find it earlier--it is a very 
compelling notion--if you find it earlier, you may be able to 
treat it better. Does it really turn into a benefit? That is 
what the randomized trials are about. But there is a lead time 
bias. If you look at a woman, and you find the woman let us say 
5 years earlier, that woman is going to live 5 years longer 
after you have found the disease. That is one of the two biases 
I talked about in my report.
    Senator Harkin. In your statement, you say that ``Women 
with breast cancer detected mammographically have extremely 
good prognosis in comparison with those having cancer detected 
any other way. Mammographically detected tumors are smaller and 
are less likely to have spread to the auxiliary lymph nodes.''
    Let me put it this way: I had a telephone conversation 
yesterday with some breast cancer survivors in Iowa, and one 
woman said about false indications, ``Well, I would rather have 
a false positive than a false negative.''
    Mr. Berry. Obviously.
    Senator Harkin. Obviously. So I do not know that there is 
any way to detect at an early stage whether a cancer is 
indolent or aggressive.
    Mr. Berry. So far not.
    Senator Harkin. So far not. Therefore, it would seem to me 
logical that if a woman could find a cancer earlier, not 
knowing whether it is indolent or aggressive, and it could be 
removed with the least invasive procedure, it would seem to me 
she would be far ahead, rather than waiting until later on.
    Mr. Berry. If you could find the first cell that mutated, 
there is no question. The issue is when between that time--and 
it becomes detectable by our current mammography--when between 
that time does it have a metastatic potential--and there, we do 
not know. It may already be doing its dastardly deeds when it 
is only a few million cells, when it cannot be detected 
mammographically.
    Senator Harkin. I do not know how to respond to that. It 
would still seem to me, again as a layman, that the earlier you 
can detect a cancer, the better your prognosis is going to be.
    Mr. Berry. There is no question about that. The question is 
does it translate into a benefit for mortality. There are 
examples--for example, the neuroblastoma issue, where we 
detected lots of cancer really early, and we found out that it 
did not convert into a mortality reduction.
    Senator Harkin. I guess we are playing some kind of a word 
game here. I do not like to put it in those terms, but it just 
seems to me, again, that if I have breast cancer, I know that 
if I wait it is going to metasticize at some point.
    Mr. Berry. Not necessarily.
    Senator Harkin. More often than not?
    Mr. Berry. No, no--well, actually, it depends on whether it 
is detected mammographically or otherwise. If it is detected 
mammographically, fewer than 50 percent will ever metasticize. 
If it is detected otherwise, something possibly greater than 50 
percent.
    Senator Harkin. Well, if it is detected mammographically, 
and fewer than 50 percent metasticize, that is because 
something has been done, right? I mean, you do not just detect 
it with mammography and say, okay, we are not going to do 
anything. Something has to be done.
    Mr. Berry. Yes, but the question, Senator Harkin, is what 
has been done. Several things have been done. One is that you 
have found more cancer, and some of the cancer that you have 
found may be incredibly important to find. I am not saying that 
mammography is not good. It may be incredibly important to 
find. But some of what you find is not important to have found. 
The problem is, of course, that we cannot distinguish which.
    Senator Harkin. Okay. I know what you are saying you would 
say to women. You would tell them all the odds and let them 
make up their own mind.
    Mr. Berry. Yes.
    Senator Harkin. But we are lay people, you know; we are not 
scientists. We want to know odds-on what is the best thing to 
do. We look to the medical community for this kind of advice 
and guidance and direction. And what I am hearing from most of 
the medical people I spoke to yesterday is that, as I said in 
my opening statement, mammography is not the sole thing, but in 
combination with other things it is a useful tool for early 
detection. And the earlier you detect it, the better your 
prognosis is going to be.
    Mr. Berry. If a woman says, ``OK, you have told me all this 
stuff and it does not make any sense to me. Just tell me 
whether to get a mammogram,'' and she says it to a doctor who 
has her best interest at heart, and the doctor says, ``I think 
you should get a mammogram,'' and she does, that is fine. I 
very much encourage that. But I want that woman to be exposed 
to--if she wants--all the information that she can digest.
    Senator Harkin. Thank you very much. My time is up.
    Thank you, Madam Chair.
    Senator Mikulski. Thank you. I think that was a very 
important exchange.
    Senator/Dr. Frist?
    Senator Frist. Thank you both for your excellent 
presentations.
    Dr. Berry, do you counsel patients at all?
    Mr. Berry. No, I do not.
    Senator Frist. Your training is a Ph.D. in biostatistics.
    Mr. Berry. That is correct.
    Senator Frist. You are being asked questions, really, that 
center on the doctor-patient relationship, and you are 
answering from statistical data and your analysis of those 
statistics.
    Mr. Berry. That is why I put it in terms of my family. My 
family listens to me--although not always.
    Senator Frist. I think that just for the audience, it is 
very important. If you hear a biostatistician looking at 
statistics and looking at the lead time bias and your 
explanation, which is very clear in your presentation and in 
your writing--I think we need to be very careful in posing 
hypothetical questions to you. If you just listen, you might 
say, here is a clinician who says he does not really--in terms 
of counseling patients regarding who should get a mammogram or 
not--and really, you should not be in that position to provide 
clinical advice to a particular patient. That is really what 
you are saying.
    Mr. Berry. That is correct. That is absolutely correct.
    Senator Frist. With that, if someone comes to a clinician 
and the clinician calls you on the phone, you will basically 
tell the clinician what you have written here. Once again, you 
are not going to say whether that patient should get a 
mammogram or not. Based on the data out there, would you ever 
feel comfortable being in a position of answering whether 
someone should get a mammogram--again, recognizing that you are 
not a clinician--as a patient or a woman who comes to you, or a 
husband, to the question of ``Should I or my wife get a 
mammogram?'' Are you comfortable advising them or counseling 
them at all, even given what you know?
    Mr. Berry. If somebody were to come to me and say, ``I am 
putting myself in your hands; you are to decide whether I get a 
mammogram,'' I would run away.
    Senator Frist. I think that is right. I think that is the 
correct answer. But it is a position that physicians are in, 
because they are looking at the biostatistical data. It is 
clearly confusing to the American people and people around the 
world where the statistics are limited and do not give the full 
answer. In your written statement, you do say that ``When it 
comes to inferring the benefits of screening, clinical 
observation is fundamentally subject to flawed 
interpretation.'' The implication of that to me is that one 
should not rely on clinical observation.
    Mr. Berry. In the context of screening. It is very 
important in the context of treatment. A doctor gives Mrs. 
Smith a treatment, and Mrs. Smith does well. He or she learns 
from that, and that is very important. What I am saying is you 
cannot learn in screening.
    Senator Frist. And the biostatistician through screening 
looks at large populations, which I think is potentially 
dangerous--inferring how you should treat a particular patient. 
That is the implication in your written testimony, and to me it 
is very dangerous as a physician to make that inference.
    Could you just comment, because people are listening to 
your interpretation of biostatistics, and they are taking down 
what you should advise the individual woman. I think that is 
dangerous as a clinician. So I just want to ask for your 
response to help me understand that. And I think that is what 
Senator Harkin is struggling with as well. In his hypothetical 
question, you answered it appropriately, but I do not think it 
leaves the correct image of what we really want to answer, and 
that is an individual woman coming in asking should she get a 
mammogram or not.
    Mr. Berry. I think there is a distinction between talking 
about the individual as an abstract and the individual as a 
particular one.
    Senator Frist. Yes, I agree.
    Mr. Berry. The individual as a particular one, I completely 
agree. The individual as an abstract, I am interested in 
communicating with particular women, with women as individuals. 
These are not policy statements that I am interested in. Other 
members of the PDQ may differ from that. I am interested in a 
particular woman's decisions and what kinds of things she 
should consider. When it comes to an individual, Jane Smith, 
that is a whole different story.
    Senator Frist. I think that is really important for us to 
understand in the hearings. The advocates, I think, will really 
be talking about individuals. But as we look at biostatistics, 
it is confusing to me as a clinician because I am in the 
business of looking at, whether it is transplantation or large 
populations, what to infer down to the patient. When I read 
what you said, ``But when it comes to inferring the benefits of 
screening''--which, again, you qualified--``clinical 
observation is fundamentally flawed or subject to flawed 
interpretation''--it is screening that is right. I did not pick 
it up, either; that is the benefit of mass screening. But when 
it comes to an individual patient, which is what both patients 
want and what physicians want, clinical observation may not be 
flawed because it really does very much determine what goes on 
with that particular patient, as you said, in that situation.
    I do not want to belabor this, but again for the broad 
audience here, I think we have to be very careful in taking 
biostatistics and saying that basically, the observations which 
are applied to screening in a statement on policy of screening 
may not apply when it comes to the individual patient. Correct 
me if I am wrong.
    Mr. Berry. I agree.
    Senator Frist. OK. I will stop there.
    Senator Mikulski. Are you sure?
    Senator Frist. Yes. Thank you.
    Senator Mikulski. First of all, Dr. Berry, I want to thank 
you for being here. And know that the rigor of the questions in 
no way challenges you and your dedication to trying to provide 
for women from your perspective the best information they need. 
So please know that the rigorous exchange is in no way 
challenging your commitment.
    Mr. Berry. Thank you very much I appreciate that.
    Senator Mikulski. I just want that on the record, and I 
think we would all concur with that.
    In time, I might come back to you, but I want to turn to 
the American Cancer Society and Dr. Eyre. I want to be clear on 
your testimony. Could you repeat what are the guidelines of the 
American Cancer Society for women to have or not have 
guidelines? What are the American Cancer Society's 
recommendations and the rationale behind them?
    Dr. Eyre. Senator, thank you for the question. Far and away 
the most important guideline for breast cancer is that women 
age 40 and older who are at average risk should have an annual 
mammogram combined with a clinical breast exam by their doctor.
    We also advocate for teaching breast self-examination 
beginning at age 20, and for women between ages 20 and 40, they 
should have a clinical breast exam by their doctor at least 
every 3 years.
    Those are our screening guidelines for breast cancer. We 
also advocate cancer prevention guidelines that speak to some 
of the points that Dr. von Eschenbach talked about. They are 
nutrition, physical activity, and modest consumption of alcohol 
at most if a person drinks, in order to do what we know how to 
do to diminish a woman's risk.
    We do have additional information about women at high risk, 
but that does not apply across the board.
    Senator Mikulski. When you say ``average risk,'' what does 
that mean. For the women and the men who love them watching 
this on TV or hearing reports on this, what would be an 
``average risk'' as they are calculating what they should be 
discussing with their physicians?
    Dr. Eyre. The average risk accounts for 70 to 80 percent of 
women in America. What we define as ``high risk'' are those 
individuals with first degree relatives with breast cancer, or 
those women who have had a breast abnormality such as atypical 
ductile hyperplasia on previous exams or biopsies, so that they 
fall into a high-risk group or the extremely high-risk group, 
those who have a genetic predisposition with the BRCA-1 or 
BRCA-2 gene.
    So we are talking about average risk individuals as those 
women who do not fall into those high-risk categories.
    Senator Mikulski. Dr. Eyre, prior to this hearing, some 
things were brought to my attention, and I do not have the 
data, but it goes to women on birth control and also women who 
have sought hormone replacement therapy.
    You have spoken very clearly, thank you, on where there is 
a genetic predisposition. But information was brought to my 
attention that women either on the pill, and now particularly 
women who are taking hormone replacement therapy seem to have 
escalating breast cancer when there has been no genetic 
propensity and so on.
    Could you comment on what you have heard and also what your 
comments might be on these issues related to hormone 
replacement therapy, in terms of the average risk and should I 
be getting a mammogram--particularly those young women who 
might be on the pill, women who are ``going through the 
change.''
    Dr. Eyre. The American Cancer Society has followed 1.2 
million Americans by using our volunteers to enroll these 
individual, and we now have 16-year follow-up data; half are 
women, and half are men. We have looked very, very carefully at 
the risk factors associated with breast cancer in women, 
including the two that you just mentioned, that is, birth 
control pills and hormone replacement therapy. With both 
prolonged use of oral contraceptives or prolonged use of 
hormone replacement therapy, the risk of developing breast 
cancer does increase over time. However, when you actually look 
at the fatality rates, those women do not have a higher death 
rate. There could be multiple answers for that. They may be 
being seen by their doctors more often, being examined, getting 
mammograms, or they could be having a cancer develop that is a 
less aggressive cancer, so that the actual death rate for women 
in those categories is nearly the same as those who do not take 
those hormones, either birth control pills or hormone 
replacement therapy.
    Senator Mikulski. Would you encourage--and ``you'' meaning 
again the American Cancer Society--those women who are either 
on the pill or who have hormone replacement therapy to get 
annual or close to annual mammograms because of this emerging 
set of information?
    Dr. Eyre. The American Cancer Society very clearly 
recommends that women discuss with their doctors all of their 
risk factors, being age, sexual status in terms of reproductive 
status and use of hormones, either as birth control pills or as 
hormone replacement therapy, their exercise level, their 
weight, etc, and together, all of those factors should be taken 
into account in determining health behavior, and one of those 
health behaviors is screening.
    We think that that adds to the impetus for a woman to have 
an annual mammogram and an annual clinical breast exam.
    Senator Mikulski. Thank you very much, Doctor. I think we 
could go through another whole line of questions particularly 
where a young women might start birth control at age 20, and 
would have 20 years of use of the pill by the time she hit 40. 
That, by my definition and I presume by yours, would be 
prolonged use and I think would raise this.
    I am now going to turn to Senator Clinton for any questions 
she might have.
    Senator Clinton. Thank you, Madam Chairman.
    I especially want to thank my colleagues, Senator Harkin 
and Senator Frist, for their very informative lines of 
questioning. I just have a few specific follow-up questions.
    Dr. Berry, in your written testimony, you have a reference 
to the audit of the Swedish trials, and you have a 
parenthetical statement that, ``Hopefully, the recently 
announced NCI guidelines will not lead to the Swedes 
withdrawing this offer.'' Could you explain what that means?
    Mr. Berry. Apparently--and I am going from what John 
Kuntzen said in the Chicago Tribune--the Swedes have agreed to 
open up their studies to audit and analysis from other 
international people, including the NCI, and this was 
apparently due to the controversy that has been going on in 
this country; they wanted to settle that controversy by doing 
what people have been asking them to do for many years. And I 
am concerned that they follow through on that, and I hope that 
these proceedings and others do not slow down that impetus.
    Senator Clinton. Well, what would it be about the NCI 
guidelines that would lead them to withdraw the offer?
    Mr. Berry. Well, there may be no more reason to open it up. 
If there were----
    Senator Clinton. The fact that the NCI reiterated their 
guidelines.
    Mr. Berry. Yes.
    Senator Clinton. OK. It is not something in addition to 
that.
    Mr. Berry. No, no, no; just less uncertainty in this 
country.
    Senator Clinton. Well, I would hope that if there are any 
Swedes out there, you do not withdraw the audit offer, because 
it seems to me that we all have a common interest in trying to 
determine what the facts are insofar as that is possible.
    Dr. Eyre, what are the international standards with respect 
to mammography? Are you aware of what the recommended standards 
are in Europe or in Canada at this point?
    Dr. Eyre. They vary depending on the health care system and 
the recommendations that they make to the public. There are a 
number of countries, including Sweden, who recommend 
mammography at age 40 or age 50, depending on the criteria that 
they use and on an every-one-to-two-year basis. Great Britain 
recommends mammography; a number of other countries do. Some in 
Europe do not recommend mammography. The issue primarily before 
this last discussion about the quality of the randomized trials 
has been on a cost-benefit analysis basis rather than on an 
issue of reduction in mortality.
    There are some countries in the world where breast cancer 
is much less common--in Asian countries--than it is in European 
or North American countries, so for many of them, it would be 
less important because of the decreased frequency, or the 
burden of the disease is less.
    In many European countries, the incidence and death rate of 
breast cancer exceeds that in the United States and Canada, and 
in those areas, some of them choose to do it, and some do not.
    Senator Clinton. Thank you very much.
    I thank both of the panelists. I guess, having heard the 
testimony thus far and certainly having reviewed the written 
testimony, I think that although there may be questions and 
certainly additional work that needs to be done, and this is 
obviously something to be weighed, I think I would weigh 
heavily the clinical experience and recommendations of Dr. Eyre 
as well as NCI, and I think that until we learn otherwise, that 
seems to be the better course of action. I appreciate the 
testimony.
    Senator Mikulski. Thank you very much.
    Mr. Berry. Senator Mikulski, can I just make one comment 
about something Dr. Eyre said, or is that out of order?
    Senator Mikulski. No. As I said, it is a comment, but 
remember, this is not a debate.
    Mr. Berry. OK. It is an occupational hazard that I have 
that I complain about people who look at particular aspects of 
data that make a point that they want to make and ignore other 
aspects.
    Dr. Eyre pointed to the Cornell study that addressed the 
Malmo trial and points out that if you look between years 8 and 
11, you get a benefit for screening. What they do not point out 
is that if you look between years 3 and 6, you get a negative 
benefit for screening. In fact, the increase in mortality 
between those years was 58 percent--30 deaths versus 19 deaths. 
That study was really very flawed, much more flawed than any of 
the trials that we are talking about.
    Senator Clinton. Well, Dr. Berry, could I ask you--as far 
as I am aware, there are only two widely utilized other forms 
of screening--either self-exam or clinical physician 
screening--is that right?
    Mr. Berry. That is as far as I know, yes.
    Senator Clinton. Right. So this is a crapshoot, right? I 
mean, part of what we are trying to figure out here is that a 
lot of women either cannot or will not do self-exams, do not 
know what they find if they do them, and a lot of doctors may 
or may not have the same clinical judgment that their neighbor 
down the hall might have.
    So in each of these instances with respect to screening, we 
are comparing, it seems to me, imperfect methods across the 
board. So part of what we are attempting to do--and I think 
Senator Frist's questions certainly got to this point--it is of 
very little benefit for most of us laypeople who are on the 
receiving end of conflicting advice to hear the difference 
between one and three and five and eight and the rest of it, 
when we have to make a judgment. And based on the best 
available information, and even based on many of the most 
unequivocal statements in your own written testimony, we put 
our odds with going ahead and having mammography, knowing, as 
we know, that it is not the perfect answer. It is like getting 
your teeth x-rayed; maybe the caries they find would never turn 
into something that you would have to have filled or have a 
tooth pulled, but you do the best you can with what information 
you have.
    Senator Mikulski. Thank you, Senator Clinton.
    This concludes this panel. We want to thank you for your 
testimony and your contributions.
    We now turn to a panel that includes the advocacy groups 
and also testimony in behalf of the American College of 
Obstetricians and Gynecologists.
    We welcome Fran Visco from the National Breast Cancer 
Coalition; Dr. Carolyn Runowicz on behalf of the American 
College of Obstetricians and Gynecologists, who is a 
constituent of Senator Clinton, and she will introduce here; 
and Dr. Leffall, chairman-elect of the Susan G. Komen Breast 
Cancer Foundation.
    Fran has been introduced by Arlen Specter, but for all 
those who have been in the women's health advocacy arena for 
some time, she is a legend for her tireless and intrepid work 
to ensure that women have access to the best health care and 
the best information. She has received many awards and is 
herself a 14-year breast cancer survivor. We look forward to 
her testimony.
    Senator Clinton, do you want to introduce the good doctor?
    Senator Clinton. Thank you very much.
    It is my pleasure to introduce Dr. Carolyn Runowicz, who is 
the vice chairman of the Department of Obstetrics and 
Gynecology at Saint Luke's Roosevelt Hospital in New York. She 
faces the dilemma of what to tell her patients about 
mammography every single day, in fact, many times a day. She is 
speaking on behalf of the American College of Obstetricians and 
Gynecologists, and I am delighted that she could be with us on 
this panel.
    Senator Mikulski. Thank you. We look forward to your 
testimony.
    We turn also to Dr. LaSalle Leffall, who is chairman-elect 
of the Susan G. Komen Breast Cancer Foundation. He comes to us 
as the chairman of the Department of Surgery at Howard 
University, a position he has held for more than 25 years, and 
he is going to serve for 1 year as chairman of the Komen 
Foundation, which of course has been one of the leading 
advocacy groups, well-known for its Race for the Cure, and for 
not only raising money but also for raising consciousness, as 
is Ms. Visco's group, which represents 60,000 individual 
members and 500 groups in terms of grassroots advocacy in terms 
of access, accuracy, and also challenging a lot of the 
attitudes of the establishment.
    Ms. Visco, we count you as a friend and an advisor, and we 
turn first to you. We are glad to see all of you.

  STATEMENTS OF FRAN VISCO, PRESIDENT, NATIONAL BREAST CANCER 
    COALITION, WASHINGTON, DC; DR.CAROLYN D. RUNOWICZ, VICE 
CHAIRMAN, DEPARTMENT OF OBSTETRICS AND GYNECOLOGY, SAINT LUKE'S 
  ROOSEVELT HOSPITAL, NEW YORK, NY, ON BEHALF OF THE AMERICAN 
  COLLEGE OF OBSTETRICIANS AND GYNECOLOGISTS; AND DR. LASALLE 
  LEFFALL, JR., CHAIRMAN-ELECT, SUSAN G. KOMEN BREAST CANCER 
                     FOUNDATION, DALLAS, TX

    Ms. Visco. Thank you, Senator Mikulski and other members of 
the committee, for inviting me to testify and for holding this 
hearing.
    You have described the National Breast Cancer Coalition, so 
I do not need to do that. But the question you have posed is 
``What do women need to know?'' Of course, the ultimate goal 
that we all share is to save women's lives.
    Unfortunately, over the years, mammography has come to be 
equated with breast cancer. Too many organizations, 
individuals, and policymakers focus their breast cancer work on 
how to get screening mammograms to healthy women. Yet you have 
heard and read much about where we are in breast cancer and 
what the future holds for this disease. We are learning more 
about the molecular basis of the disease. There is much more 
emphasis on how to prevent this disease from occurring to begin 
with. We are talking more about the environmental links to 
breast cancer. We are looking at targeted therapies. We are 
understanding that there are many different types of breast 
cancer, and we are beginning to learn how to treat them.
    How do we detect breast cancer at its very early stages, 
and if so, do we know what to do with it?
    These are many of the questions that we are working on 
today. It is an exciting time in breast cancer, and while we do 
not have answers, there is much work to be done that will take 
billions of dollars and much attention.
    Yet we continue to spend billions of dollars on 
mammography. Where is this other money going to come from? 
These are priorities that must be set based on solid scientific 
evidence.
    I want to make a couple of comments in response to 
statements that were made earlier. First of all, we must be 
clear that mammograms do not prevent breast cancer. We really 
do not know how to prevent breast cancer for any individual 
woman.
    No. 2, the data show that there are more mastectomies in 
the groups in the trials that are screened by mammography than 
in the control groups. That is an important point when we begin 
to talk about quality of life in this issue.
    Also, it is important to know that biostatisticians are 
experts in this debate; they are experts in looking at clinical 
trials, designing them, and interpreting data on which clinical 
decisions must be made.
    But again, your question is ``What do women need to know?'' 
Well, they need to know the truth. Our goal should not be to 
provide a clear, simple message. Our goal here should be let us 
find the truth about what will save women's lives, and let us 
get that information and those interventions to women.
    A clear, simple message, while comforting, is not 
necessarily correct. This is an incredibly complex issue, as 
you can tell--lead time bias, length bias. There are renowned 
scientists on every side of this issue, questions about the 
trials, many of which are important substantive questions; 
questions about how to interpret results, what are the risks--
and a false positive is not the only risk of a mammogram--what 
are the benefits, how do we quantify them.
    We cannot pretend that this complexity and these 
controversies do not exist, and it cannot be resolved simply by 
issuing a clear, simple guideline.
    I am not going to address the complexities of the trials. I 
was a reviewer for the U.S. Preventive Task Force. I disagreed 
with their recommendations. I have spent a great deal of time 
analyzing the information, analyzing the data, and my written 
testimony addresses those issues--my written testimony which I 
submit for the record together with the Question and Answer 
that the National Breast Cancer Coalition has put together for 
the public on these issues.
    I trust women. I think women are quite capable of 
understanding complexity and dealing with medical uncertainty. 
At the National Breast Cancer Coalition, we have developed a 
number of programs to educate the public about these issues, to 
give them the tools to enable them to deal with the uncertainty 
and to seize the power to make informed decisions. This 
includes the Q and A I referenced, a number of science and 
advocacy training programs.
    So the goal is truth, not just clarity and a simple 
message; and the truth seems to be that there is uncertainty 
about the evidence or about the existence, or if it exists, the 
extent of the benefits of screening mammography. Some will say 
30 percent reduction in mortality, others will say 20, some 
will say none. We have heard about lead time and length bias; 
do we save lives or simply add days to lives.
    These are all legitimate issues that women are capable of 
understanding and making their own choices on.
    I have just two more quick points. If the goal is to save 
women's lives, if we had taken the billions of dollars put into 
building an infrastructure for screening mammography and breast 
self-exam videos and shower cards, and provided health 
insurance for the women of this country, I think we would have 
saved many more lives.
    A woman testified on behalf of the Coalition last year for 
the CDC treatment legislation about her support group sharing 
one prescription for tamoxifen because the other women did not 
have health coverage. That is the reality of what women with 
breast cancer are facing. And again, that would save more 
lives--I believe even the most ardent supporter of mammography 
screening would admit that.
    So let us focus our efforts now on getting an independent 
review of the Swedish data on the screening trials by an 
organization such as MedicoLegal Investigations in the UK; let 
us get the best possible answer we can for women under the 
circumstances, and let us move on. Let us find out how to 
prevent this disease, how to detect it truly early, how to get 
nontoxic therapies, and how to get quality care to all women. 
And finally, let us reauthorize the Mammography Quality 
Standards Act, because diagnostic mammography will continue, as 
will screening mammography, and we need to make certain that it 
is done well.
    Thank you very much.
    Senator Mikulski. Thank you, Ms. Visco. As always, you 
raise eyebrows.
    [The prepared statement of Ms. Visco follows:]
                    Prepared Statement of Fran Visco
    Thank you, Chairmen, members of the Senate Health, Education, Labor 
and Pensions Aging Subcommittee, and members of the Senate 
Appropriations Labor, Health and Human Services and Education 
Subcommittee, for your dedication and leadership in working with the 
National Breast Cancer Coalition (NBCC) in our fight to eradicate 
breast cancer.
    I am Fran Visco, a breast cancer survivor, a wife and mother, a 
lawyer, and President of the National Breast Cancer Coalition.
    The National Breast Cancer Coalition is a grassroots organization 
dedicated to ending breast cancer through the power of action and 
advocacy. The Coalition's main goals are to increase Federal funding 
for breast cancer research and collaborate with the scientific 
community to design and implement new models of research; improve 
access to high quality health care and breast cancer clinical trials 
for all women; and, expand the influence of breast cancer advocates in 
all aspects of the breast cancer decision making process.
    On behalf of NBCC, which is made up of more than 600 member 
organizations and 70,000 individual members, I would like to thank you 
for the opportunity to testify today on this critically important 
issue.
    I believe it's very important to put the current debate about the 
effectiveness of screening mammography in the right context. What this 
debate is really about is saving women's lives, and improving the 
quality of their lives--not about attacking or defending mammography. 
For decades, mammography has been linked to preventing breast cancer 
deaths. We used to think that the earlier we catch breast cancer, the 
easier it will be to treat. Yet, we are beginning to better understand 
the complexities of this disease. And we are realizing that the concept 
of early detection being the key to reducing mortality may not be the 
whole story. Some very small cancers can be very aggressive, regardless 
of when they are detected, and other big tumors caught later may never 
cause a death. We must consider screening mammography, not only in 
terms of how early and effectively it detects tumors, but also in terms 
of the impact early detection will have on a woman's treatment options 
in light of what we now know about this disease.
    We also must be clear about the realities and limitations of the 
early detection tools that exist today. Currently, there is no truly 
early detection. Often, by the time a tumor is found, it has been in 
the breast for 6 to 10 years. The goal must be to detect the tumors at 
their earliest stage, or prevent them in the first place.
    Mammography should be accepted for what it is: followed by 
treatment, it may extend the lives of some women who have breast 
cancer, but it does not prevent or cure breast cancer, and it has many 
limitations.
    At best, this is simply not good enough. We need more reliable and 
less invasive tools developed to detect breast cancer. We need more 
targeted and more effective treatments for this disease and a better 
understanding of how one tumor differs from another. And, we need a 
clearer understanding of what causes this disease, and how to prevent 
it.
    It is also important to keep in mind that this debate is not about 
diagnostic mammography (for women with symptoms of breast cancer), but 
about screening mammography (the healthy population of women). This 
issue must be considered in the context of the limited health care 
dollars available for breast cancer. What are the best use of resources 
to reduce mortality and improve quality of life for women?
    The National Breast Cancer Coalition respects the difficult 
challenge in developing a public health message, which may differ from 
the personal decisions that individual women and their doctors will 
make. But, our goal today is to explain what we do and do not know 
about how to reduce breast cancer mortality. The truth is not always 
clear, but we believe that women deserve to be fully informed, and that 
they are capable of understanding the complexities around this disease.
                               background
    The National Breast Cancer Coalition believes that the debate over 
the effectiveness of mammography in reducing breast cancer mortality is 
vitally important. For too long, mammography has been inextricably and 
erroneously linked with ``prevention'' of breast cancer. Mammography 
screening of women age 40 and above has become the standard of care for 
women in the United States. It has become a multi-billion dollar 
business. Organizations exist solely to raise awareness about 
mammograms and breast self-examination. Legislation has proposed to 
teach high school students about breast self-examination. Campaigns 
directed to the public about the importance of screening are increasing 
in number. For much of the public, mammography is the most important, 
if not the only, issue in breast cancer.
    Women are told that early detection saves lives. Yet, the evidence 
of mortality reduction from screening is conflicting and continues to 
be questioned by scientists, policy makers and some members of the 
public. Breast self examination has become part of the culture of 
breast cancer, even though there is no evidence whatsoever to support 
its efficacy.
    The fact that breast cancer screening is now high on this nation's 
agenda must not color the analysis of the evidence. Recommendations on 
breast cancer screening must have as their goal saving women's lives, 
not preserving an infrastructure.
    In my testimony today, I will make four major points.
    First, I will explain NBCC's position on mammography screening.
    Second, I will respond to the recent studies about what more we now 
know regarding the effectiveness of mammography reducing mortality.
    Third, I will discuss what these new data mean for women, and for 
the decisions they must make.
    Finally, I will give NBCC's recommendations for where we need to go 
from here.
     the national breast cancer coalition's position on screening 
                              mammography
    The National Breast Cancer Coalition has long acknowledged the 
limitations of mammography screening. For years, NBCC has said that 
mammography is not the answer to the breast cancer epidemic. Although 
it may be difficult to accept, it is vital that women know the truth 
about breast cancer screening and the false sense of security it 
provides. As breast cancer activists, NBCC welcomes the long overdue 
criticism and discussion of the effectiveness of existing breast cancer 
screening methods.
    We must accept that we do not know how to detect breast cancer 
truly early or how to prevent or cure this disease. Instead, we should 
focus our attention on getting those answers. NBCC believes the goal 
must be to focus research efforts on true prevention and on stopping 
breast cancer from occurring altogether. We must work together to find 
new, more accurate ways to detect and treat this disease.
    The Coalition also believes that women who have access to 
mammography must have access to treatment. Screening alone does not 
reduce mortality. It is for that reason that NBCC was proud to be the 
originators, and lead advocates on working with Members of Congress, 
many who sit on your Committees, to enact the Breast and Cervical 
Cancer Treatment Act in the 106th Congress. As you know, this law 
ensures that low-income women screened and diagnosed with breast cancer 
through Federal programs can now have access to the treatment they 
need. NBCC had to fight four, very long, hard years to get women in 
this program treated as well as screened. There was a lot of opposition 
along the way, mainly because people were afraid that we were 
criticizing screening. This debate must not be about saving screening, 
but rather, about reducing breast cancer mortality. It is about women's 
lives.
    NBCC also believes that mammography should be of the highest 
quality possible. The Coalition commends your Committees' leadership in 
enacting the Mammography Quality Standards Act (MQSA), which 
established minimum national quality standards for mammography 
facilities and personnel as well as a rigorous annual inspection 
program to ensure those standards are being met. We appreciated the 
opportunity to testify before Congress during reauthorization of this 
program in 1998, at which time we urged that the women be notified 
directly of the results of their mammogram, and that Congress continue 
to ensure the highest quality mammography by maintaining the rigorous 
inspection process initially contemplated.
    NBCC supports reauthorization of this important program this year, 
and would be happy to provide the Committee with additional information 
or recommendations.
                    nbcc's response to the evidence
    The National Breast Cancer Coalition's general position on 
mammography is that guidelines on mammography screening should only be 
issued if scientific studies prove that such programs save lives, and 
if the benefits outweigh the risks.
    As your Committees know, there are seven published randomized 
trials of mammography screening. The oldest of these trials, the New 
York Trial, was conducted in the 1960's. Four of the trials were 
conducted in Sweden, one was conducted in Canada, one was conducted in 
the United Kingdom, and one was conducted in the United States. The 
seven trials are known as:
    The New York trial or HIP trial--enrolled women 40-64
    The Malmo trial--enrolled women 45-69
    The Two-County trial--enrolled women over age 40
    The Edinburgh trial--enrolled women ages 45-64
    The Canadian trial (parts 1 and 2)--enrolled women ages 40-59
    The Stockholm trial--enrolled women ages 40-64
    The Goteborg trial--enrolled women ages 39-5
    Two of these trials--the Malmo and Canadian trials--found that 
mammography did not benefit women. In these trials, the women who got 
mammography screening had the same breast cancer mortality as the women 
who did not. The other five trials found that mammography did benefit 
women and reduce breast cancer mortality by about 30% on average. 
Although a majority (five of seven) of the trials found that 
mammography is beneficial, we cannot simply conclude that mammography 
saves lives.
    First, the reliability and quality of each trial must be evaluated. 
Some trials may have been poorly carried out, and some trials may not 
be applicable to the general population of women. Also, it is important 
to note that a majority of trials does not necessarily represent a 
majority in the number of individuals who participated in the trials.
    Many scientists have critiqued these trials, however, the most 
thorough peer reviewed evaluation to date was recently conducted by 
Drs. Gotzsche and Olsen, Danish scientists affiliated with the well-
respected Cochrane Collaboration. These scientists set out to review 
and evaluate all seven of the mammography trials to determine the 
quality of each. The authors had no conflicts of interest and were 
unbiased at the start of the review. Their findings were published in a 
recent issue of The Lancet medical journal as a systematic review.
    The findings of the systematic review prompted an independent panel 
of experts (the PDQ screening and prevention editorial board) at the 
National Cancer Institute to conduct its own evaluation of the seven 
mammography trials. After its review, the panel concluded that there is 
insufficient evidence to show that mammography screening prevents 
breast cancer deaths in any age group of women. Moreover, it concurred 
with Drs. Goetze and Olsen that the Malmo and Canadian trials were the 
highest quality trials, and that they did not show that mammography 
reduces breast cancer mortality. Finally, the review found that 
mammography could also have negative effects--including more aggressive 
treatment and more unnecessary surgeries.
    The authors of the systematic review do not state that there is 
proof that mammography is ineffective. Rather, the evidence is unclear.
    Most recently, the U.S. Preventive Services Task Force (USPSTF) 
recommended screening mammography, with or without clinical breast 
examination, every one to two years for women ages 40 and over. The 
Department of Health and Human Services (HHS), and the National Cancer 
Institute (NCI), have endorsed these recommendations.
    NBCC believes that these recommendations were premature and that 
the Task Force should not have made recommendations until the 
individual data is released by the Swedish investigators and analyzed 
by an independent review.
    It seems clear that in a situation like the present, where data 
exist that could answer the questions posed, those data should be 
released and analyzed before recommendations are made. In addition, the 
fact that data exist that could help answer the question of whether 
screening results in fewer breast cancer deaths, but more deaths from 
other types cancer or other causes, should have compelled the Task 
Force to demand the data before it made recommendations.
    Moreover, the Task Force relied on evidence to recommend screening 
mammography for women age 40-49 that clearly does not rise to a level 
sufficient to support screening. In fact, only one trial was designed 
to answer the question of screening in women aged 40-49, and it found 
no benefit. In the remaining trials, women in that age group were a 
cohort of the larger population. In previous recommendations, the Task 
Force did not recommend screening women in this age group; since there 
is no new data to show a benefit for these women, it is unclear why the 
Task Force changed its recommendation.
   what does this mean for women trying to make informed healthcare 
                               decisions?
    The National Breast Cancer Coalition believes strongly that women 
deserve to know the truth. If the truth is that evidence is unclear, 
then they should know that. Progress in eradicating breast cancer means 
accepting uncertainty regarding best treatment and detection methods. 
Women and doctors have to understand, and live with this uncertainty, 
understand the risks, and make individual decisions.
    This issue is not black and white. The public needs to accept 
uncertainty, and move toward educating themselves so they can make 
their own decisions on an individual basis. Women are capable of 
understanding that to date, no screening tool allows for truly early 
detection of breast cancer. Meaning, by the time a tumor is detected, 
it has been in the breast for 6-10 years. Women also need to understand 
that some cancers will never spread to other parts of the body, so 
detecting these cancers won't save lives--rather, treatment would be 
unnecessary, and possibly harmful. We just don't know.
                       where do we go from here?
    First, the National Breast Cancer Coalition believes that the most 
useful thing we can do now is make certain that there is an independent 
review of the data. NBCC would like to first better understand what the 
results of these trials mean. The Swedish researchers must allow all of 
the individual data to be released to an independent reviewer like 
Medico Legal Investigations, Ltd. in Knebworth, England. This may 
resolve many of the concerns and questions raised by Drs. Gotzsche and 
Olsen, and may provide better answers about the effectiveness of 
mammography.
    Second, the cost of mammograms cannot be ignored. Remember, we are 
not talking here about women who have been diagnosed with a disease. We 
are talking about the screening of a healthy population of women. 
Mammography screening is a multi-billion dollar expenditure. We must 
ask ourselves whether this is the best expenditure of finite dollars? 
Especially in light of the fact that we know using these resources to 
buy healthcare for underserved and uninsured women would unquestionably 
reduce mortality.
    We must ask the critical questions: What is the best use of 
resources? What are the pros and cons? This is a debate that must 
happen. These are the issues that we must grapple with before we decide 
to just accept the status quo.
    Finally, NBCC urges the public not to just sit and fret over the 
lack of clear consensus on mammography. Instead, we need to be 
advocating for more research and resources going towards true 
prevention and better methods of treatment and detection.
    Precious time, resources and attention continue to be diverted away 
from promising research and funneled into an oversold panacea for 
breast cancer detection. The issue is about saving women's lives, not 
saving the institution of mammography. We must continue to look ahead 
of the curve to see what more can be done regarding prevention and 
detection. Only then will we be able to eradicate this disease.
    I want to thank these Committees for the opportunity to testify 
today. I have enclosed NBCC's Question and Answer document on 
mammography, and ask that it be included in the record. I would be 
happy to answer any questions.

    Senator Mikulski. Dr. Runowicz, please.
    Dr. Runowicz. Good afternoon, Madam Chair and distinguished 
members of the subcommittee. I appreciate your invitation to 
testify today on behalf of the American College of 
Obstetricians and Gynecologists, or as it is better known, 
ACOG.
    I am a practicing physician who is no stranger to dealing 
with concerned patients when scientific controversies raise 
questions about their health and safety. In this particular 
debate, I also wear a third hat--I am a 10-year breast cancer 
survivor.
    The American College of Obstetricians and Gynecologists 
represents nearly 40,000 physicians dedicated to improving 
women's health care. Our members are seeing women on the front 
lines of the breast cancer struggle. We provide women with 
clinical breast exams, refer them most often for mammography, 
and often make the diagnosis of breast cancer. Some of us, like 
myself, are also gynecologic oncologists and assist in the 
treatment plan.
    ACOG agrees that an extensive and objective reassessment of 
all mammography data may be justified. Until further reanalysis 
of the data is conducted, ACOG continues to recommend 
mammography screening every one to 2 years for women in their 
40's and annual mammograms beginning at age 50.
    We are here today because of publicity surrounding a study 
done by Danish researchers recently published in Lancet. The 
Lancet study questions one of the most widely held beliefs in 
preventive medicine--that screening healthy people for cancer 
and detecting it early saves lives. It is important to note 
that this is not a new study but a reanalysis of already 
existing published data.
    Scientific debate on critical issues like this one is 
common. ACOG supports periodic, evidence-based, peer-reviewed 
analysis of all available data on mammography, including a 
review of studies like the one in Lancet. We take its criticism 
of prior mammography research very seriously, and we want to 
make sure that the Lancet study itself stands up to rigorous 
review.
    In fact, the U.S. Preventive Services Task Force announced 
last week a different conclusion than that of the Lancet study. 
Their review of the data found that breast cancer deaths among 
women randomized to screening in seven trials that included 
women older than 50 showed a 23 percent reduction in mortality. 
And contrary to prior testimony that you have heard today, in 
1993, an independent analysis of the actual data from the five 
Swedish trials cited in the Lancet study showed a statistically 
significant 24 percent reduction in breast cancer mortality in 
the screened group.
    With such conflicting data, where do we go from here?
    Initially, I think that all of us--Members of Congress, 
doctors, patients, journalists, researchers--need to understand 
the difference between the very rigorous standards that 
scientific evidence must meet to clearly prove the worth of a 
test and the proctocolitis of what must be done in physicians' 
offices when conclusive scientific evidence (1) is not yet 
available or (2) may never be available.
    I make this second point because at this time and in the 
future, there would be clear ethical and moral problems in 
performing a randomized prospective clinical trial in breast 
cancer screening that medical scientists say are the highest 
qualify of scientific proof. How many women today would be 
willing to go without breast cancer screening in a clinical 
trial to prove or disprove a statistical point? We may have to 
live with a certain amount of uncertainty when it comes to the 
results of mammographic screening trials.
    I also think we need to educate our patients about the 
facts behind the recent media hype--and that is what this is 
all about--media hype. While the Lancet study has raised 
several important issues, as a practicing physician, I have to 
look at this through the eyes of individual patients. I explain 
to patients that this debate has nothing to do with the 
effectiveness of breast cancer treatment. There is agreement 
that treatment saves lives. Instead, the debate is whether 
earlier treatment made possible by the early detection of 
tumors is better than later treatment.
    I tell them that early treatment made possible by early 
detection does make a difference. I explain why I think the 
accumulation of research trial evidence over the years has 
strengthened the science behind breast cancer screening and 
that the data in aggregate demonstrate improved health 
outcomes, with benefits outweighing the harmful effects.
    I discuss the recent controversy and my own 
recommendations. I explain that scientific debate on critical 
issues is common, but well-established guidelines should be 
followed unless there is compelling evidence to alter or 
abandon them.
    The news stories have already had a large impact on 
patients. They are confused, and they express a loss of faith 
and confidence in mammography. Some even misinterpret the media 
coverage and take away the message that mammography is bad and 
even causes cancer.
    Over the years, we have made significant strides in 
educating women about mammography by breaking down financial, 
physical, and psychological barriers to women seeking 
mammographic screening. I fear, as does ACOG, that these 
barriers might be reinforced by this negative attention and 
uncertainty generated by the media hype.
    As already mentioned by Senator Mikulski, I and ACOG are 
also deeply concerned that the ongoing controversy might 
discourage health insurance plans from covering this important 
screening tool.
    As frustrating as this controversy may be to women 
suffering from breast cancer, the silver lining is that it 
brings to light a goal that we all share--the need to be even 
more vigilant in supporting research efforts to enhance not 
just early detection, but treatment as well as prevention and 
finding a cure for breast cancer. Until then, mammography 
remains as one of a number of strategies that can help save or 
improve women's lives.
    Even if the screening tests that we have now are not as 
good or as conclusive as we would like, they are the best we 
have at the moment. As a practicing physician, I would be 
derelict in my duties if I advised women to stop having 
mammograms.
    On behalf of ACOG and my patients, I thank you for holding 
this hearing and for the opportunity to testify today. I would 
be happy to answer questions.
    Senator Mikulski. Thank you very much, Doctor.
    [The prepared statement of Dr. Runowicz follows:]
            Prepared Statement of Carolyn D. Runowicz, M.D.
    My name is Carolyn D. Runowicz, and I appreciate your invitation to 
testify today. I appear before you on behalf of the American College of 
Obstetricians and Gynecologists (ACOG), and as a practicing physician 
who is no stranger to dealing with concerned patients when scientific 
controversies raise questions about their health and safety. In this 
particular debate, I also wear a third hat: I am a 10-year breast 
cancer survivor.
    The American College of Obstetricians and Gynecologists (ACOG) 
represents nearly 40,000 physicians dedicated to improving women's 
health care. Ninety-five percent of board-certified obstetricians and 
gynecologists in the United States are members of ACOG. Our members are 
seeing women on the front lines of the breast cancer struggle: we 
provide women with clinical breast exams, refer them most often for 
mammography, and often make the diagnosis. Some of us, like myself, are 
gynecologic oncologists and assist in treatment plans.
    I am currently Vice Chair of the Department of Obstetrics and 
Gynecology at St. Luke's-Roosevelt Hospital in New York City. I also 
serve as Director of Gynecologic Oncology Research for the Women's 
Health Service Line of Continuum Health Partners, Inc. and I am 
Professor of Obstetrics, Gynecology and Women's Health at Albert 
Einstein College of Medicine (AECOM). Since 1994, I have chaired the 
gynecologic subcommittee of the Breast Cancer Prevention Trials that 
are part of the National Surgical Adjuvant Breast and Bowel Project.
    ACOG agrees that an extensive and objective reassessment of all 
mammography data may be justified. In fact, ACOG continually updates 
its own clinical recommendations by periodically reviewing all data. 
Until further reanalysis of the data is conducted, ACOG continues to 
recommend mammography screening every one to two years for women in 
their forties and annual mammograms beginning at age 50.
    We are here today because of publicity surrounding a study done by 
Danish researchers, members of the Cochrane Collaboration, recently 
published in Lancet (referred to here as the Lancet study). The Lancet 
study questions one of the most widely held beliefs in preventive 
medicine: that screening healthy people for cancer and detecting it 
early saves lives. It is important to note that this is not a new 
study, but a re-analysis of published data.
    Scientific debate on critical issues like this one is common. ACOG 
supports periodic, evidence-based, peer-reviewed analysis of all 
available data on mammography--including a review of studies like the 
one in Lancet. We take its criticism of prior mammography research very 
seriously, and we want to make sure the Lancet study itself stands up 
to rigorous review.
    In fact, the U.S. Preventive Services Task Force (USPSTF) announced 
last week a different conclusion than that of the Lancet study. The 
USPSTF review of the data found that the pooled effect size of the 
combined trials was sizable and statistically significant. Breast 
cancer death among women randomized to screening in seven trials that 
included women older than 50 showed a 23 percent reduction in 
mortality.
    In addition, an earlier independent analysis of individual-level 
data from the five Swedish trials cited in the Lancet study, conducted 
under the auspices of the Swedish board of health and published in 
1993, showed a statistically significant 24 percent reduction in breast 
cancer mortality in the screened group.
    With such conflicting data, where do we go from here?
    Initially, I think all of us--members of Congress, doctors, 
patients, journalists, or researchers--need to understand the 
difference between the very rigorous standards that scientific evidence 
must meet to clearly prove the worth of a test, and the practicalities 
of what must be done in physicians' offices when conclusive scientific 
evidence (1) is not yet available, or (2) may never be available.
    I make this second point because at this time and in the future 
there would be clear ethical and moral problems in performing the 
randomized, prospective clinical trials in breast cancer screening that 
medical scientists say are the highest quality of scientific proof. I 
ask you: how many women today would be willing to go without breast 
cancer screening in a clinical trial to prove or disprove a medical 
researcher's point? We may have to live with a certain amount of 
uncertainty, when it comes to the results of mammographic screening 
trials.
    I also think we need to educate our patients about the facts behind 
the recent media hype on the usefulness of mammography. While the 
Lancet study has raised several important issues and I am very 
interested in the scientific debate, as a practicing physician I have 
to look at this through the eyes of individual patients.
    It is important to explain to our patients that this debate has 
nothing to do with the effectiveness of breast cancer treatment. There 
is agreement that treatment saves lives. Instead, the debate is whether 
earlier treatment made possible by early detection of tumors is better 
than later treatment.
    Then I explain why I believe that early treatment does make a 
difference. I am very careful to explain to women that early diagnosis 
combined with early treatment translates for many women into a better 
future. I believe that early detection in most cases helps us to 
prolong women's lives, even those destined to die from breast cancer. 
Early diagnosis can affect the quality of women's lives in positive 
ways.
    I explain why I think the accumulation of research trial evidence 
over the years has strengthened the science behind breast cancer 
screening. There has been an important decline in death rates from 
breast cancer, nearly 2 percent every year during the 1990s and nearly 
4 percent since the mid-90s, which has been attributed to improvements 
in treatment and a trend towards earlier detection. In the 1980s, only 
13 percent of U.S. women were getting mammograms and the average size 
of tumors was 3cm. By the late 1990s, 60 percent of women were having 
regular mammograms and the average size of tumors decreased to 2cm.
    So, I note that although mammography is not a perfect screening 
tool, it is very effective. Mammography can have false-positive 
results, which may cause anxiety, biopsies, and cost--although these 
diminish from ages 40-70. However, the data in aggregate demonstrate 
improved health outcomes, with benefits outweighing the harmful 
effects.
    I discuss the controversy and my own recommendations noting of 
course that the decision on whether to be screened is theirs. I explain 
that scientific debate on critical issues is common, but well-
established guidelines should be followed unless there is compelling 
evidence to alter or abandon them.
    The news stories have already had a large impact on patients. They 
are confused and express a loss of faith and confidence in mammography. 
Some misinterpret the media coverage and take away the message that 
mammography is ``bad'' and can even cause cancer!
    Over the years, we have made significant strides in educating women 
about mammography by breaking down financial, physical, and 
psychological barriers to women seeking mammography screening. I fear 
that existing barriers and negative attitudes towards mammography might 
be reinforced by the negative attention and uncertainty generated by 
the media hype. It is too soon to know if women will turn away en masse 
from mammography and we will turn the clock back in the fight to treat 
breast cancer. I am also deeply concerned that the ongoing controversy 
about the value of screening mammography might discourage health 
insurance plans from covering this important screening tool.
    As frustrating as this controversy may be to the women suffering 
from breast cancer, the silver lining is that it brings to light a goal 
I think we all share: the need to be even more vigilant in supporting 
research efforts to enhance not just early detection but also 
treatment, as well as prevention and finding a cure for breast cancer. 
Until then, mammography remains as one of a number of strategies that 
can help save or improve women's lives.
    Even if the screening tests we have now are not as good or as 
conclusive as we would like, they are the best we have at the moment. 
As a practicing physician, I would be derelict in my duties if I 
advised women to stop having mammograms.
    On behalf of ACOG and my patients, I thank you for holding this 
hearing and for the opportunity to testify today. I am happy to answer 
any questions.

    Senator Mikulski. Dr. Leffall, we would be happy to hear 
your testimony in behalf of the Komen Foundation.
    Dr. Leffall. Thank you very much, Senator Mikulski and 
other distinguished members of the committee.
    As a surgeon oncologist and medical educator, I have 
devoted most of my professional life to the study of cancer. 
After I completed my surgical oncology training and Memorial 
Sloan Kettering Cancer Center and 2 years in the Army, I 
returned to Howard University in 1962 and have been there since 
then, so this is now my 41st year on the surgical faculty at 
Howard and my 41st year in the active practice of surgical 
oncology, and the major part of my practice consists of 
patients who have breast problems; thus my major interest in 
this.
    The Komen Foundation was established some 20 years ago by 
Nancy Brinker to honor the memory of her sister, Susan Goodman 
Komen, who died of breast cancer at the age of 36. Today the 
Komen Foundation is the Nation's largest private funding 
sources of breast cancer research and community-based outreach 
programs.
    Modern medicine is fully of uncertainty, but today the 
assault on mammography has created a cloud of confusion and an 
atmosphere of suspicion. It has also done a true injustice to 
American women who understand that screening is not prevention. 
We are not surprised, but certainly we are disappointed.
    That said, we concur with the expert opinion of our times--
mammography is an imperfect screening tool and one that should 
be made better. But we want to emphasize that we think it is 
the most appropriate thing now for women, screening 
mammography.
    While we are working to unlock the secrets of what causes 
breast cancer and eventually prevent the disease for future 
generations of women, the Komen Foundation understands the 
realities facing women and their families today. Therefore, the 
Foundation applauds the mammography screening recommendations 
reported last week by the U.S. Preventive Services Task Force 
and the National Cancer Institute.
    Affiliates of the Komen Foundation currently provide grants 
for more than 1,600 breast health education and breast cancer 
screening and treatment projects in their communities. In 
addition, the Komen Foundation Research Program awarded more 
than $20 million in grants during the last year alone to 
support cutting-edge research in institutions around the globe.
    As someone who is on the front lines and seeing patients 
every day with breast problems, many of whom have breast 
cancer, I know firsthand how both mammography and breast cancer 
treatment have changed during the last 20 years. Mammography is 
better. The radiologists are better. The technicians are 
better.
    Two of the crown jewels of health care policy in the United 
States, both of which came about in the last decade, are the 
Mammography Quality Standards Act and the CDC's Breast and 
Cervical Cancer Early Detection Program. Senator Mikulski, the 
Komen Foundation applauds your efforts and being a leader in 
the MQSA. It is so important to ensure the high quality of 
mammography for women. We know that quality mammography 
certainly saves lives.
    Mammography screening to reduce breast cancer mortality 
must be sensitive enough to detect the disease. Poor-quality 
mammography reduces the sensitivity and specificity of the 
screening test. The use of dedicated, up-to-date equipment is 
key to the performance of high-quality screening tests. Since 
the MQSA enactment, women throughout this country have gained 
further confidence in their mammogram.
    My next statement was alluded to by Senator Murray earlier 
today. In the early 1980's, when only 13 percent of women in 
the United States were getting mammograms, the average tumor 
size at detection was about 3 centimeters. By the late 1990's, 
when 60 percent were getting mammograms, the average detected 
tumor size was 2 centimeters. For many women, early detection 
means the possibility of less invasive treatments in some cases 
as well as the option of breast conservation surgery instead of 
mastectomy.
    In the past decade, breast cancer mortality rates have 
declined in the United States, and Dr. von Eschenbach showed 
that on his charts. This is due in large measure to early 
detection and timely treatment. That is important--early 
detection and timely treatment.
    Regular mammography as part of a three-step breast health 
regimen that includes monthly breast self-exams and annual 
clinical exams saves lives. It enables women, as true partners 
in their health care, to become familiar with the normal look 
and feel of their breasts.
    While mammography can sometimes lead to false negative 
results when a woman and her caregiver discover a suspicious 
lump that did not show up on a mammogram, further examination 
does not always entail surgery. We have means now of making a 
diagnosis with image-guided biopsies and tests like that.
    There is also the risk of false positive results, and an 
abnormal mammogram is in fact not breast cancer, which may also 
result in further tests.
    But while these risks may result in unnecessary procedures 
for some women, our constituents in America's communities tell 
us that even these serious consequences seem acceptable if they 
are faced with the possibility of a life-threatening disease.
    We encourage the Senate to allow steadfast hearts and large 
minds to rule the day and advocate instead for the 
recommendation of the U.S. Preventive Services Task Force to 
take advantage of the only widely available screening tool 
currently proven to find breast cancers before they grow to the 
size that can be felt by hand.
    The National Cancer Institute declares that the evidence 
will not support a change in their recommendations. We at the 
Komen Foundation will remain true to our recommendations as 
well.
    Thank you for this opportunity to appear before you today, 
Senator Clinton and Senator Mikulski.
    [The prepared statement of Dr. Leffall follows:]
          Prepared Statement of LaSalle D. Leffall, Jr., M.D.
    On behalf of the Susan G. Komen Breast Cancer Foundation, thank you 
Senator Mikulski, Senator Harkin, Senator Frist, and Senator Specter 
and other committee members here today, thank you for creating a forum 
for public discussion on the most recent debate on breast health.
    The Komen Foundation is one of the largest private funding sources 
for breast cancer research today, and was begun by Nancy Brinker 20 
years ago in honor of her sister, Susan Goodman Komen, who died of 
breast cancer at the age of 36. Helen Keller has long been a hero of 
Nancy's, and she once said, ``Doubt and mistrust are the mere panic of 
timid imagination, which the steadfast heart will conquer, and the 
large mind transcend.''
    Modern medicine is full of uncertainty . . . This can be 
purposeful, however, for it is uncertainty which lends life its 
fascination when partnered with the desire to comprehend. But today, 
the assault on mammography has created a cloud of confusion, an 
atmosphere of suspicion, and an injured party of women. Discounting the 
power of uncertainty, the recent debate has thrust ambiguity upon this 
significant subject of public health. Unproductive reiteration of the 
relative merits of various scientific inquiries has created confusion. 
We're not surprised, but we are disappointed.
    Imagine two computers on one hand, and a couple of mastermind 
logicians on the other, testing which group analyzes chess moves more 
advantageously. Would you be surprised if your results were conflicting 
if one computer had a Pentium Chip, and the other did not?
    The ``Pentium Chips'' of Mammography in the United States are the 
Mammography Quality Standards Act, the BCCEDP, and other new 
initiatives of the last decade. The vast improvements in film, 
machinery, training, and access are part and parcel to mammography's 
``Pentium Chip''.
    That said, we concur with the expert opinion of our times. 
Mammography is an imperfect screening tool. We are investing heavily in 
better technologies. Yet, we know improvements take time. So while we 
are working to improve early detection and eventually uncover true 
forms of prevention, the Susan G. Komen Breast Cancer Foundation 
applauds the mammography screening recommendations reported last week 
by the U.S. Preventative Services Task Force and the National Cancer 
Institute.
    The Komen Foundation will continue to recommend the three-step 
approach to positive breast health including monthly self breast 
examinations beginning at age 20; clinical breast examinations at least 
once every three years beginning at age 20 and annually after age 40; 
and annual screening mammography beginning at age 40.
    The Task Force's recommendations, underscored by Secretary 
Thompson's remarks, take us one step closer to clearing the confusion. 
Because, before women start canceling screening mammography 
appointments, we need clear guidelines for those making the decision 
today about their health care based on the best currently available 
information and technology. Until a foolproof mechanism of detection is 
widely available, the Komen Foundation strongly encourages women to 
continue having mammograms.
    At the same time, the Komen Foundation will continue to focus 
research dollars on improving the quality of screening technology as 
well as research that will one day lead to a cure for breast cancer. 
The Komen Foundation Research Program awarded more than $2.4 million in 
grants last year to support institutions conducting cutting-edge 
imaging technology research.
    In total, the Komen Foundation awarded $20 million in research 
grants last year in support of the fight against breast cancer, it's 
eventual cure, prevention and eradication. In addition, Komen 
Affiliates provided grants for more than 1,600 breast health education, 
screening and treatment projects in 116 communities across the country.
    Since 1998, the Komen Foundation Research Program has funded grants 
to improve breast imaging technology totaling $3,320,927. We have also 
funded considerable research aimed at finding a way to cure or prevent 
breast cancer, to wit: proteins associated with breast cancer totaling 
$4,786,144; Angiogenesis totaling $754,148; Oncogenes totaling 
$1,845,348; Growth Factors totaling $4,051,553; Antibodies totaling 
$2,998,787; and BRCA genetic abnormalities totaling $2,082,024. Please 
find detailed information about grants in each category as an addendum 
to my testimony.
    The benefit of early detection is undisputed, but with it comes the 
potential risks for additional procedures and/or over-treatment. 
``False-positive'' results may lead to further imaging or biopsy that 
end up with a benign finding. When there are historic data (i.e., 
previous mammograms) for comparison, however, the rate of false 
positives can be decreased, thus the need for regular screening rather 
than a one-time view only.
    The detection of breast cancers that may never have progressed to a 
dangerous stage during a patient's lifetime also counts toward the 
``risk'' side of the equation. But since we don't know which breast 
cancers will progress, virtually all these women are treated 
surgically, with or without radiation and chemotherapy. And while these 
risks may result in unnecessary procedures or treatment for some women, 
our constituents in America's communities tell us that even these 
serious consequences seem acceptable if they are faced with the 
possibility of a life-threatening disease.
    Mammography can also sometimes lead to false-negative results. For 
this reason, when a woman and her caregiver discover a suspicious lump 
that did not show up on a mammogram, it should be examined by other 
means--but that doesn't always entail surgery. There are well-accepted 
alternative ways of assessing whether a lump detected through clinical 
exam, or even an abnormal mammogram, is breast cancer other than 
through surgical biopsies. These methods include MRI, ultrasound, and 
ultrasound-guided or stereotactic (x-ray guided) biopsy. The cost of 
making a breast cancer diagnosis is lowered dramatically by appropriate 
use of ultrasound and image-guided biopsies.
    So, while we have the potential for false-negative and false-
positive findings on the one hand, we have the case for early detection 
on the other. The larger the tumor, the longer or faster it has been 
growing. This often translates into more aggressive treatment, as 
larger tumors are more likely to have spread beyond the initial site. 
And even with more treatment, the survival chances of women with larger 
tumors is not as good as those with tumors smaller in size.
    As previously stated, the Komen Foundation is funding research into 
new imaging technology with a goal of diminishing false-positive and 
false-negative outcomes. Further, and more critically, we are funding 
research to identify which tumors in which women are likely to spread 
aggressively and become life-threatening. Our funding of studies of 
molecular markers associated with breast cancer or other abnormalities, 
including inherited genetic changes, tumor growth factors and gene 
proteins, totaled nearly $3 million in 2001 alone.
    In the early 1980's, when only 13 percent of women in the U.S. were 
getting mammograms, the average tumor size at detection was about 3cm. 
By the late 1990's, when 60 percent were getting mammograms, the 
average detected tumor size was 2cm. For many women, early detection 
also means the option of breast conserving surgery, instead of a 
mastectomy.
    Mortality rates have also declined in the U.S. in the past decade. 
Some argue that lowered mortality rates for breast cancer may be 
attributable to better treatment options rather than early detection. 
It is intriguing however, to review data compare from countries that do 
and do not have national screening programs. The breast cancer 
screening program in Sweden is arguably the most comprehensive in the 
world. Denmark, Sweden's Scandinavian neighbor to the South, does not 
have a screening program. Germany also does not have a comprehensive 
screening program and never has. The U.S. has a growing program of 
mammography screening, with Medicare and Medicaid coverage, CDC 
programs, and private insurers.
    The incidence of breast cancer per 100,000 population is lower in 
Germany than in the Sweden; lower in Denmark than in the U.S. 
Nonetheless, the ratio of mortality to incidence rate (which 
approximates the percentage of people who will die from the disease) is 
far lower in Sweden (22 percent) and the U.S. (23 percent) compared to 
Germany (32 percent) and Denmark (36 percent).

------------------------------------------------------------------------
             Country                Incidence    Mortality      Ratio
------------------------------------------------------------------------
Sweden...........................        81.03        17.48          22%
United States....................        91.39        21.22          26%
Germany..........................        73.65        23.74          32%
Denmark..........................        86.15        29.16          36%
------------------------------------------------------------------------

    Further, the rate of mortality decline in Germany and Denmark have 
not kept pace with the declines in the U.S. Between 1990 and 1996 (the 
last year of data for all four countries), breast cancer mortality 
declined 12 percent in the U.S. and 8 percent in Sweden, compared to 1 
percent in Denmark and Germany.

------------------------------------------------------------------------
             Country                   1990         1996       %change
------------------------------------------------------------------------
Denmark..........................        26.88        27.25          -1%
Germany..........................        21.87        22.03          -1%
Sweden...........................        17.80        16.39           8%
United States....................        22.54        19.75          12%
------------------------------------------------------------------------

    Dr. Gabriel Hortobagyi, of M.D. Anderson, believes that both early 
diagnosis and treatment play an important role in the decrease, 
stating, ``The available data would indicate that early diagnosis would 
reduce risk of mortality by about 25-30 percent and that optimal 
adjuvant chemotherapy plus hormonal therapy would reduce risk of 
mortality by about 30-45 percent. However, neither approach has been 
applied to its full potential--not every woman between ages 40 and 65 
has annual mammograms, and not everybody with primary breast cancer 
larger than 1cm receives optimal adjuvant systemic therapy.'' It is 
interesting to consider therefore, that the decrease in mortality 
observed in the U.S. may be only a fraction of the decrease one would 
observe, were both early detection and optimal timely treatment be 
available to all eligible women.
    The Komen Foundation appreciates the significant role economics 
play in screening, and that new interventions must also be cost-
effective. However, we cannot align ourselves with a ``bottom line'' 
philosophy, as therein the cheapest patient is a dead patient. Thus, 
while we consider all screening and treatment with an eye toward cost-
effectiveness, the Komen Foundation still puts faith in a procedure 
that yes, holds elements of uncertainty, but also holds proof of lives 
saved.
    There are unanswered questions, not only behind mammography, but 
also behind its debate. What has really spurred this vigorous 
deliberation yet again? If the opponents of mammography vehemently deny 
substantial benefits, arguing instead that the risks tip the scales 
unfavorably, why then is there no call for a national ``cease and 
desist'' for all screening?
    There is always a role for economics, but if that's the heart of 
this debate, then lay it on the table and have it examined objectively. 
If there's an argument for spending public and private dollars on 
research rather than screening, then it too should be aired for public 
examination.
    To truly eradicate breast cancer, we must not only meet the 
immediate needs of women facing this disease today, but we must also 
invest in research for future generations. This is how grants are made 
at Komen--investing in tomorrow and today. But even then, the fight is 
not won. The greatest tragedy would be to discover that elusive cure or 
prevention and not be able to get it into the hands of each and every 
person who needs it, regardless of where they live or their ability to 
pay.
    Clearly, the issues of risk and economics need to be spoken in a 
language women will understand. And for that, we encourage the members 
of these two committees to review this issue carefully to resolve the 
unanswered questions and confusion surrounding the risks of 
mammography. It is too hard to argue that a decrease in deaths of 
American women due to breast cancer is not related to a link in 
awareness and its sister messages of early detection and annual 
screening.
    Women are in a quandary. Will you send the message to your mothers, 
sisters, aunts, wives and daughters to wait for a lump to be felt to 
find their breast cancer, even when we are able to find it much 
earlier? Public Health is in a quandary. Will even low-cost, effective 
screening methods be disallowed in a time of tightened healthcare 
budgets? And researchers are in a quandary. Will their years of 
research be allowed to go fallow due to politically motivated debate?
    Rather, let us allow ``steadfast hearts'' and ``large minds'' to 
rule the day, and advocate instead for the recommendation of the U.S. 
Preventative Services Task Force: take advantage of the only widely 
available screening tool we currently have proven to find breast 
cancers before they grow to the size that can be felt by hand. The ACS 
sees no reason to change its screening recommendation. The NCI declares 
that the evidence will not support a change in their recommendations. 
We at the Komen Foundation will remain true to ours as well. Thank you 
for this opportunity to appear before you today.

    Senator Mikulski. Thank you very much.
    Senator Clinton, I am happy to do the wrap-up questions; if 
you want to go first and lead off this round, we are happy to 
have you do so.
    Senator Clinton. Thank you very much.
    I want to thank the panelists. We have three extremely 
dedicated witnesses who have given their lives to this fight 
against breast cancer.
    I could not agree more with the point that Fran Visco made 
about the inequitable distribution of resources with respect to 
dealing with breast cancer. In fact, most of our major health 
problems are more likely to fall disproportionately on the 
poor, on the people who do not have access to affordable, 
quality, reliable health insurance. I think that the National 
Breast Cancer Coalition's constant advocacy on behalf of more 
resources and better access has been an extremely important 
part of this debate, and I hope that it is not a point that is 
going to be forgotten, because we still have a lot of work to 
do.
    I want to ask Fran about what the Coalition's current 
review of insurance coverage with respect to not only 
mammography but to breast cancer treatment in general has led 
you to conclude about any action that we need to be 
contemplating with respect to insurance coverage.
    Ms. Visco. I think one of the most important issues before 
the Congress now is coverage for oral anti-cancer drugs. As you 
know, breast cancer is primarily a disease of older women. 
Medicare does not cover tamoxifen, which is probably 
responsible for much of the decrease in mortality that you have 
seen in the charts that Dr. von Eschenbach put up. That is a 
critically important question in breast cancer, much more 
important than if a woman has to wait 3 months for a screening 
mammogram.
    I also want to say that there is no way that the National 
Breast Cancer Coalition would let up on pushing for access to 
health care for all women and all Americans.
    Another point that I need to have the opportunity to make 
is about breast self-exam. There is no scientific evidence that 
breast self-exams save lives. That is another infrastructure 
that has been built up in this country based on no evidence, 
and in fact the evidence that we are seeing now indicates that 
there may not be a difference in mortality through teaching 
breast self-exam.
    Senator Clinton. Thank you.
    Dr. Runowicz, I really appreciate your perspective, both as 
a physician and as a breast cancer survivor yourself. What is 
the best way for us to dispel the confusion and to some extent 
even more than that, the despair that women feel about knowing 
what they are supposed to do and who they can believe and how 
they make the decisions. I think that what the American Cancer 
Society and the National Cancer Institute and others have said, 
which is, I think, putting it sort of simply, that you cannot 
let the perfect be the enemy of the good, and until we know 
something more than we know now, it is prudent to continue to 
recommend the same standards that we have adopted.
    How do we get that message out?
    Dr. Runowicz. I think that is a very big challenge, and one 
article on the front page of The New York Times can undo all 
the good of all of the organizations. But I think that 
hammering home the same consistent message and letting patients 
know that controversy is what science is all about, and that is 
how we make new discoveries, but until we have other data that 
make us change these guidelines, these guidelines are based on 
good science, and we need to get that message out over and over 
again.
    Senator Clinton. I thank you for your role in doing that.
    And Dr. Leffall, thank you for your years of service to 
patients and as an advocate and spokesman. From your 
perspective also dealing with patients and from the Komen 
Foundation work that you do, is there more that we could do in 
the Congress to try to convey more support for the clinicians' 
work that you and Dr. Runowicz and others are doing? How can we 
help you get the message out, and from your perspective, what 
additional steps should we be taking in funding to try to move 
the breast cancer debate beyond mammography to prevention and 
cure and some of the other issues that are at the root of it?
    Dr. Leffall. We must always be concerned about those, 
Senator Clinton, prevention and cure. But one thing that I 
think you can do--so many of my colleagues who are radiologists 
are now telling me that they are no longer willing to perform 
mammography because the reimbursement they receive is not worth 
it from a pragmatic point of view. They say, ``I want to help 
patients''--that is why we are in medicine, to help patients--
``and I do not get enough to pay the expense in my office.''
    So that is something that certainly can be done, but in 
addition to that, as long as we can continue to emphasize that 
until we have something better, the things that are based on 
science--and the mammography recommendations are based on 
scientific data--and we are not opposed to other people looking 
at those data to be sure that they are what they say they are, 
and if there is a difference of opinion, let us talk about it; 
let us not try to hide it. But that is something that we can do 
for the radiologists who perform mammography.
    Senator Clinton. Thank you, because as I said earlier, that 
is a big problem in New York and is becoming a real barrier to 
access, so that even if women are presented with all sides of 
this issue and make the determination that they want a 
mammogram, it is becoming harder to get one, either because of 
access or affordability.
    Dr. Leffall. That is correct.
    Senator Clinton. I want to again thank Chairman Mikulski 
for holding this important hearing along with Chairman Harkin. 
It was a very important service.
    Senator Mikulski. Thank you very much.
    Senator Harkin?
    Senator Harkin. Thank you very much, Madam Chairman.
    Dr. Leffall, regarding one point you just mentioned, I just 
want to say that I do have a bill in to increase that 
reimbursement rate for radiologists. I have been hearing from 
them, and just yesterday in Iowa the question was asked as to 
what does a mammogram cost. They said $100 to $120, somewhere 
in that range. I think the reimbursement is now around $75; is 
that right?
    Dr. Leffall. Average.
    Senator Harkin. Average about $75?
    Dr. Leffall. Yes.
    Senator Harkin. So you are right--a lot of people are just 
turning people away.
    Dr. Leffall. They are not doing it anymore; that is 
correct, Senator.
    Senator Harkin. So I do have a bill in to get the 
reimbursement raised, and if I can find something to attach it 
to this year, I will attach it.
    Dr. Leffall. Very well.
    Senator Harkin. I am wondering, though, if I will get 
comments on the floor that maybe this is not necessary. I don't 
know. Is it necessary? With the confusion that seems to be out 
there now, people will say, ``Why do you want to increase the 
reimbursement rate to radiologists who do mammograms when we do 
not even know if mammograms are effective? Maybe we should not 
do it.''
    Dr. Leffall. But most groups in the United States believe 
that until we get something better, this is what we should 
continue to recommend. That is why the Komen Foundation is 
recommending it, ACOG, NCI, the American Cancer Society--
because we believe that it is based on the available science 
that we have today. And we would like to emphasize that we are 
not opposed to a re-look at the data to be sure that it is what 
we say it is, and let patients know the truth. We are not 
trying to hide the truth. But when you come up with something 
better--and Dr. von Eschenbach mentioned some things like the 
PET scan, MRI, digital mammography--when they prove to better, 
we can go to that, but until then, I think we should stick with 
what we have that we know can make the diagnosis early. And you 
have asked many questions today about early detection, which is 
extremely important.
    Senator Harkin. Fran Visco, we have worked together now for 
over 10 years.
    Ms. Visco. Yes, that is right.
    Senator Harkin. You said in your testimony that we have got 
to ask if mammography screening is the best use of finite 
dollars. Well, if not, then, what do we do?
    Ms. Visco. Well, I think we should use them to give health 
coverage to women. I think that women need to be reimbursed for 
their medicine. I think that more women need to have access to 
quality care. There are many areas that are looking at truly 
early detection, looking at how to prevent breast cancer, 
looking at nontoxic targeted therapies.
    The mammography debate is sucking up all of our time, all 
of our dollars, all of our attention, all of our focus. There 
is so much more to eradicating breast cancer, and that is where 
we need to move those dollars.
    Senator Harkin. How much do we spend yearly on mammography?
    Ms. Visco. It is a multibillion-dollar number; exactly how 
many billions, I do not know. I have seen numbers recently, but 
they are not in my head; I know that it was many billions.
    Senator Harkin. Are most covered by insurance and 
Medicare--mostly Medicare?
    Ms. Visco. Probably. I do not know the answer to that 
question.
    Senator Harkin. I would like to find that out.
    Senator Mikulski. But not for the poor. Senator, just in 
the interest of a little dialogue, you have Medicare covering 
mammography, but that is every other year--but at least it is 
something, and we spearheaded that. Then, those of us who have 
private insurance receive reimbursement, but again, you have 
got to watch your time on that, or they will not cover that. 
But for poor women, the only thing that we have is the breast 
and cervical screening program at CDC, which the women of 
Congress initiated and, Senator, you have been steadfast in 
helping provide the funds for it.
    Did you hear what I just said? [Laughter.]
    Senator Harkin. I am sorry. Everybody is talking to me at 
one time.
    Senator Mikulski. I said that for reimbursement, Medicare 
provides it for the women over 65 every other year; for other 
women, it is reimbursed through private health insurance, and 
again, it has age guidelines; third, for poor women, the only 
tool--and it is a down-payment tool--is for the breast and 
cervical cancer screening at CDC, and that is funded through--
--
    Ms. Visco. The treatment component that we worked on for 4 
years and last year, we were finally successful in getting 
enacted into law, where women who are screened through the CDC 
program, once they are diagnosed, become Medicaid-eligible for 
their treatment.
    Senator Mikulski. That is right. But you fund in Labor-HHS 
the CDC program; but if it were not for your funding in the CDC 
program, poor women would not even have an option--and by and 
large, even there, it is still a rather spartan number of women 
who can participate. But even when they are screened, the 
Medicaid is also an option to the State.
    Ms. Visco. It is an optional program with the States, but 
the National Breast Cancer Coalition has been very successful 
over the past year in getting 39 States so far to opt in.
    Senator Mikulski. Bravo, bravo for that.
    Ms. Visco. Thank you.
    Senator Mikulski. But again, for poor women--you see.
    Senator Harkin. My staff tells me the amount spent on 
mammograms yearly is $3 billion. I assume that it is all 
covered by insurance and Medicare. So it is a sizeable sum of 
money. We are up to $800 million into research now; right?
    Ms. Visco. Yes.
    Senator Harkin. We finance $800 million for breast cancer 
research. So it is a lot of money for mammography.
    Ms. Visco. And remember, access to health care, too, for 
these women to treatment and to oral anti-cancer drugs--very 
important issues in breast cancer.
    Senator Harkin. Well, again, we're trying to clear this up 
and trying to get a definitive answer to women out there. What 
would you tell my nieces? Both of their mothers died of breast 
cancer. They are now in their late 30's now, maybe almost 40, 
and they have been getting breast cancer screening because of 
that. What would you tell them?
    Ms. Visco. I would tell them to go to the National Breast 
Cancer Coalition website and look at our question-and-answer, 
which lays out all of the issues on this very debate, and we 
would be happy to help them work their way through it, and then 
they can make up their minds about what they want to do. But I 
think women have the power and the capability to understand 
this complexity and to make a decision on what to do.
    Senator Harkin. I believe that is true also, but I think 
early detection right now is still the best.
    Ms. Visco. We may not know how to detect breast cancer 
early enough.
    Senator Harkin. I know that. I read that in your testimony.
    Ms. Visco. Believe me, I wish----
    Senator Harkin. And we are working on the blood test, as we 
did for ovarian cancer. That might be possible for breast 
cancer. They are working on it now. But in the meantime we do 
not have it. It might not be early enough, but finding it with 
mammography is earlier than detecting it during a physical 
exam.
    Ms. Visco. But the issue is does it make a difference, and 
that is the debate around the trials.
    Senator Harkin. I thought the answer to that was, all other 
things being equal, yes, it makes a difference. The earlier you 
detect it, the better the quality of life and the higher 
probability of having a longer life.
    Ms. Visco. Let me respond that the data do not necessarily 
show that in terms of length of life, but certainly quality of 
life. The data from the trials show that more mastectomies are 
performed in the group that is screened by mammography than in 
the control group, because we do not know how to treat very 
early breast cancer, and we tend to do mastectomies often in 
that population.
    Senator Harkin. Or lumpectomies, or something like that.
    Ms. Visco. Yes, but the data show that more mastectomies 
are done in the mammography screened group. That is the data.
    Senator Harkin. But that data from the sixties, seventies 
and eighties.
    Senator Mikulski. And now we have new approaches.
    Senator Harkin. Yes, we have new approaches now. That is 
why I keep saying the Danish study does not take into account 
some of the new technologies and new interventions that we use 
now.
    Ms. Visco. OK. I know we can have this debate forever, and 
again, I believe that our Q and A lays out some of these 
issues, and perhaps it warrants a longer debate at another 
time. But sometimes breast cancer is not a very logical 
disease; it is a very complex disease.
    Senator Harkin. Well again I ask, as I asked the other 
panelists: all things being equal, if someone has the insurance 
coverage or if they are low-income and can get access to the 
breast and cervical cancer screening program, should they go 
ahead and have a mammogram?
    Every single person I talked to yesterday in my State of 
Iowa answered yes. These were clinicians, doctors, nurses, and 
breast cancer survivors. Every single one said yes. I am not a 
doctor and I would not give advice, but I think one of the 
purposes of our hearing is to try to clear the air a little and 
get a little more clarity for the women of this country.
    You are right, women can make up their own minds----
    Ms. Visco. Yes.
    Senator Harkin [continuing]. But it is very difficult to 
make up your mind when you are faced with a life-threatening 
illness, and the people in whom you put your trust and 
confidence do not have definitive answers or clear guidelines 
for you.
    I keep coming back to my basic question: all other things 
being equal, is early detection better than later detection, 
and will mammography give you earlier detection?
    Dr. Runowicz, what do you say?
    Dr. Runowicz. I would like to answer several of the 
questions that you have raised. On your nieces, there has been 
a breast cancer prevention trial that has been completed in 
this country and showed that tamoxifen prevented breast cancer, 
and there is the STAR study now. If they meet the eligibility 
criteria--and I do not think they will because they are not 
postmenopausal--but I would certainly encourage that they look 
into clinical trials and that they certainly discuss the issue 
of tamoxifen.
    As far as right now, there is no compelling evidence to 
alter any of our guidelines. Every, single major institution, 
every, single major organization, is still saying ``Stick with 
your guidelines,'' which are from age 40 to 50 every one to 2 
years--some organizations are every year, such as the American 
Cancer Society; others are every one to two, such as the 
National Cancer Institute, and the American College of Ob-Gyn--
after 50, every year until there is another comorbid condition 
which precludes the sensibility of continuing mammography.
    The debate here today is a statistical debate. The debate 
here today is media hype. The debate here today is The New York 
Times front page. That is why we are here today. We are not 
here because there is new data. We are here because there are 
statisticians who, in their own group, the Cochrane group, 
which is an excellent group--these two investigators did not 
have the entire group behind them, and the Lancet article that 
they published was not published with the entire backing of 
that group. Instead, that group published a separate article, 
and they have their website, where dissension from the two 
authors.
    That is why we are here today--because somebody has 
reanalyzed data, and they have chosen, based on their 
statistical evaluation, that they wish to exclude other 
studies, to which other groups like the U.S. Preventive 
Services Health Task Force said no, we do not agree with their 
exclusions.
    So looking at the raw data again--and it has been done in 
1993--but looking at that raw data again will perhaps readdress 
these issues. But there is no compelling evidence, there is no 
new evidence, to alter our guidelines.
    Was that clear?
    Senator Harkin. That is very clear.
    Dr. Leffall. Senator, I would just like to echo--you asked 
the question about your nieces--without any question, I believe 
the answer is yes, please get the screening mammogram. And this 
is not saying you are opposed to any of the other things that 
have been mentioned today in terms of access to care. What 
could be more important than access to health care? It is one 
of the most important things. But today we are talking about 
the mammography debate, and it is a debate, a statistical 
debate.
    But I think Dr. Frist, a colleague, mentioned it. When you 
are sitting with a patient, and that patient--once again, you 
go with a lot of information--they say, ``You are asking me to 
make a decision in a few minutes, and you have spent your 
entire professional life studying this. I do not think you are 
being fair to me.'' I would get that when I used to go into a 
lot of detail; yet you try to inform patients. Patients should 
be informed. Patients are very intelligent. They should be 
informed. But when we cut through the chaff to get to the 
wheat--get the screening mammogram--that is the answer.
    Senator Harkin. Thank you all very much. I appreciate it.
    Senator Mikulski. Before we conclude--because I said I 
would be the wrap-up questioner--I just want to reiterate 
essentially what has come out of this hearing and then have a 
final question for you, Doctor.
    First of all, what we see is that the biostatisticians 
disagree. That is clear. And they will continue to look at data 
and analyze it.
    Clinicians, those who have the lives of patients in their 
hands, do not disagree that clinicians agree and recommend in 
the most enthusiastic, unabashed, and unqualified way that we 
follow the existing guidelines that have been established by 
the National Cancer Institute, recently reaffirmed by the 
Preventive Services Task Force at HHS, and have also been the 
longstanding recommendations of the American Cancer Society.
    So this hearing should not end without it being clear that 
those who are in charge of America's public health, its 
research institutes, the oldest cancer organization in the 
United States of America, and representing the clinicians all 
agree that if you are 40 or older, you should have a mammogram 
every other year, and if there is indication of greater risk, 
either genetically or because of medications, to pursue it.
    That is where there is agreement. There is also agreement, 
whether it is among the biostatisticians or among the advocacy 
groups, where again there is disagreement.
    But first of all, yes, we need access. We need access to 
women's health care. And as part of that, if you have access to 
health care, your doctor can then recommend what are the best 
next steps. It could be diabetes; it could be lung cancer, 
which is the biggest killer of women; it could be heart 
disease, etc. But we need access to health care, and then, 
access also to treatments, which means the way we need to look 
at our patients' bill of rights. I believe, Doctor, that ob-
gyns should be designated also as primary care providers. You 
are the first and sometimes the only physician that women see, 
and you are the one who can say, ``Wow, 20 years on birth 
control--we had better get you in now, even though you are 38 
years old.'' So access is important.
    Of course, this debate is moot for the poor because of 
limited access to health care and the even further limited 
nature of access to treatments, even where there is diagnosis. 
We have all heard that.
    I thank all of you for mentioning the mammogram quality 
standards as well as the Cervical and Breast Screening Act at 
CDC.
    Thanks to the advocacy groups, and Fran, I particularly 
want to mention your group. We really pushed for that. I take 
pride that I was one of the prime movers of that initially, and 
then we had these fine men of the Senate really support us. We 
now know that it has made a difference, and we welcome any 
views on the mammogram quality standards, so we thank you for 
that.
    So that is where we agree. We agree that we have got to 
have our mammogram quality standards. We agree that we need 
research on new tools and on new treatments--but new tools and 
new treatments are a hollow opportunity if we do not have 
access to health care for women, and the start for what is the 
best way to go for whatever we confront really needs to start 
with access to health care.
    So that, then, is where I think we agree, and I think if 
people ask me, ``What do you think about all this, Senator?'' I 
would say that we need to stay the course in terms of the 
existing guidelines until there is clear, compelling, and 
convincing evidence otherwise. We really need to pursue these 
mammogram quality standards as well as new research.
    I am going to close with the access issue. I have raised 
this issue, as have Senator Clinton and others. We have got to 
be really careful that while we scientifically disagree, we do 
not end up discouraging health insurance plans from covering 
this important screening tool. It might not be the best tool 
right now, although it seems to be the only reliable, or at 
least pretty reliable, tool. In fact, we would like the health 
insurance industry to take a whole new, fresh look at women's 
health care and what they reimburse, starting with designating 
the ob-gyn as the primary care physician, along with other 
internists.
    So we say to the insurance companies that we hope you have 
learned something, and we say most of all to American women 
that if you are over 40, get a mammogram; if you are under 40, 
let us find a way to get you in to talk to someone to see if 
you are at risk and go from there.
    Thank you very much. I really want to thank everyone who 
presented their views today, and to the biostatisticians, thank 
you even for your disputed presentations, because they have 
caused us now to take a new look at where we are. So we thank 
you, and we encourage you to continue in your own good work.
    This hearing stands adjourned.
    [Additional material follows:]

                          ADDITIONAL MATERIAL

          Prepared Statement of Claudia I. Henschke, PhD, M.D.
    Our testimony on behalf of mammography screening is based on our 
recent article published in The Lancet on February 2, 2002 
\1\ \2\ \3\. We there responded to the 
publication by Olsen and Gotzsche (also published in The Lancet, 
October 20, 2001) in which they concluded that of the seven major 
mammography studies, five were severely biased and thus could not be 
used to evaluate mammography. They stated that neither of the remaining 
two (Malmo and Canadian) studies considered to be acceptable showed a 
benefit.
---------------------------------------------------------------------------
    \1\ .abMiettinen OS, Henschke CI, Pasmantier MW, Smith JP, Libby 
DM, Yankelevitz DF. Mammographic screening: no reliable supporting 
evidence? Lancet 2002;358:404-06.
    \2\ .abMiettinen OS, Henschke CI, Pasmantier MW, Smith JP, Libby 
DM, Yankelevitz DF. Mammographic screening: no reliable supporting 
evidence? BM__1__www.theLancet.com.
    \3\ .abLetter to the editor. Lancet 2002, Feb 23. In press.
---------------------------------------------------------------------------
    In our paper, we focused on the Malmo and Canadian studies that 
Olsen and Gotzsche deemed acceptable to illustrate that they, among 
many others, ignored larger and even more fundamental flaws in their 
analyses and that this lack of understanding led them to produce 
misleading, falsely nihilistic evidence. These fundamental flaws are 
inherent in the currently prevailing approach to assessment of any 
screening test for cancer: the failure to continue screening long 
enough in a study for its benefit to become evident and the failure to 
assess that resulting benefit, namely the reduction of cancer deaths, 
during a relevant time period, that is, sufficient distant from the 
onset of the screening program. If the approach is flawed, conclusions 
drawn from such an evaluation will also be flawed.
    We showed that in the Malmo study, mammography provided for a 55% 
reduction in the breast-cancer case-fatality rate in women 55 years and 
older and about a 30% reduction in those aged 45 to 54. This benefit, 
however, only became evident after six years of screening, that is from 
the seventh year of screening onward. It was only in the Malmo study 
that screening was not discontinued prematurely as had been done in the 
Canadian study.
    It should be self evident that when a screening test picks up a 
cancer and this cancer is cured by the early intervention provided by 
the early detection, the death that would have otherwise occurred in 
the absence of screening would have been at some point in the future, 
typically years later. The better the screening test, the earlier the 
detection, the longer the time required before the evidence of the 
benefit becomes apparent. Thus, when assessing the screening benefit, 
screening must continue for sufficiently long to recognize the deaths 
which were prevented in the screened group as compared to the control 
group. Many studies have been done to evaluate mammography, yet we 
still are left in a state of confusion. This situation should not be 
repeated with screening for other cancers. Thus, we endorse these 
public hearings, but plead that before anything else, the fundamentals 
of research on screening for cancer be re-examined in open discussions. 
Some current examples of the now prevailing flawed approach are worth 
noting.
    The National Cancer Institute (NCI) is about to embark on a new 
trial to evaluate spiral CT for lung cancer. This study will cost 
approximately $300 million (approximately the same amount the U.S. is 
planning to spend on rebuilding Afghanistan), will last 10 years, and 
its current design exhibits the same fundamental flaws that we have 
addressed. The ongoing PLCO (Prostate, Lung, Colon, Ovary) screening 
study currently underway, started in 1993 and projected to last until 
2014, is the most expensive screening study ever performed by NCI until 
the recently contemplated spiral CT study. The PLCO costs approximately 
$150 million. It similarly ignores the fundamental principles we 
addressed. We therefore expect both of these studies to yield 
misleading results. In addition, these studies take so many years to 
complete that the screening they seek to evaluate may well be obsolete 
by the time the study is completed. For example, the lung component of 
the PLCO will evaluate the chest x-ray screening for lung cancer. In 
1993 this may have been a reasonable consideration; by 1999, it was 
clear that spiral CT was far superior in detecting early lung cancer, 
and by 2014, even spiral CT likely will be outdated.
                                UPMC Health System,
                                 Pittsburgh, PA 15213-3180,
                                                 February 21, 2002.
Hon. Arlen Specter,
U.S. Senate,
Washington, D.C. 20510.
    Dear Senator Specter: I am the Director of the Breast Program at 
the Magee-Womens Hospital/University of Pittsburgh Cancer Institute and 
the protocol chairman for the National Surgical Adjuvant Breast and 
Bowel Project STAR trial, the Study of Tamoxifen and Raloxifene that is 
funded by the National Cancer Institute. I understand that on February 
28 you will be participating in a Labor, Health and Human Services and 
Education Appropriations Subcommittee and the Health, Education, Labor 
and Pensions Public Health Subcommittee joint hearing on mammography. 
As you prepare for this hearing, I wanted to bring to your attention 
another important weapon in our battle against breast cancer--breast 
cancer risk assessment.
    While the debate over mammography is critically important, the 
statistics show that mammography alone is not enough. In addition to 
mammography and other tools for early detection, attention also needs 
to be focused on prediction and prevention--identifying those women who 
are at highest risk for breast cancer, and intervening to prevent them 
from developing breast cancer in the first place. Fortunately, women at 
high-risk now have several ways to reduce their risk and help prevent 
breast cancer. However, these options all involve difficult risk/
benefit decisions, which heightens the importance of better predicting 
which women are most likely to benefit from early, preventative 
intervention.
    One approach to refining our predictive abilities is to move risk 
assessment from statistics to science. Along with evaluating a woman's 
family history, age and other general risk factors, we now have 
biologically-based risk assessment tools to consider. For example, 
ductal lavage is a procedure in which the cells lining the milk ducts 
are collected and analyzed under a microscope to determine whether they 
are abnormal. Published studies demonstrate that high-risk women with 
atypical milk duct cells have a significantly increased, near-term risk 
of developing breast cancer. Using such individualized risk 
information, we can identify women at very high risk for breast cancer 
and better target our ability to offer them risk reduction options.
    Because of my commitment to encouraging the routine practice of 
risk assessment among breast care specialists, I am currently serving 
as the chair of the Risk Assessment Working Group (RAWG), which 
consists of 13 leading breast specialists. On February 27, 2002, 
members of the RAWG will participate in the first risk assessment 
symposium of its kind at the 19th Annual Miami Breast Cancer 
Conference. At the conference, we will be presenting a consensus Risk 
Management Strategy, which will help guide breast specialists in the 
practice of risk assessment and the management of high-risk women. I 
have attached copies of two posters on breast cancer risk assessment 
and ductal lavage that will be presented at the Miami conference. 
Following the conference, the RAWG plans to broadly distribute the 
guidelines to the breast health community and pursue publication in a 
peer-reviewed journal.
    As more prevention options become available for women at high risk 
of breast cancer, individualized risk assessment becomes increasingly 
important. I would like to stress, however, that neither risk 
assessment nor ductal lavage are substitutes for breast cancer 
screening. Rather, they are intended to serve as adjuncts to 
mammography and breast physical examinations. Early detection and 
preventative measures are both critical to our fight against breast 
cancer.
    I hope that you will submit my letter to the record, so that you 
can share this important information about breast cancer risk 
assessment with your colleagues. Please feel free to call me at (412) 
641-6500 if you have any questions or if I may be of further assistance 
to you or your staff. Thank you for your leadership on this and other 
important women's health issues.
            Sincerely yours,
                            Victor G. Vogel, MD, MHS, FACP,
                            Professor of Medicine and Epidemiology,
                               Director, Magee/UPCI Breast Program.
                                 ______
                                 
  Prepared Statement of the Agency for Healthcare Research and Quality
    The Agency for Healthcare Research and Quality (AHRQ) respectfully 
submits the following testimony on the effectiveness of screening 
mammography for the record.
    Today's hearing is very timely in light of the recommendation from 
the U.S. Preventive Services Task Force (USPSTF) released last week on 
February 21, 2002, by HHS Secretary Tommy G. Thompson. The USPSTF is a 
leading independent panel of private-sector experts in prevention and 
primary care sponsored by AHRQ that conducts rigorous, impartial 
assessments of scientific evidence for a broad range of preventive 
services. In its new recommendation, the USPSTF endorsed screening 
mammography every 1-2 years for women ages 40 and over.
    AHRQ's mission is to support research designed to improve the 
outcomes and quality of health care, reduce its costs, address patient 
safety and medical errors, and broaden access to effective services. 
The research sponsored, conducted, and disseminated by AHRQ provides 
information that helps people make better decisions about health care.
    With this mission, AHRQ-funded research activities provide 
meaningful, evidence-based information on screening mammography to 
women and their clinicians. The Agency does this in three ways: first, 
supporting research that informs the quality of mammography and 
interpretation of mammograms; second, supporting a review of the up-to-
date evidence on mammography screening by the U.S. Preventive Services 
Task Force (USPSTF); and third, developing evidence-based materials for 
patients and clinicians.
                           quality mammograms
    Screening mammography is an important tool for reducing deaths from 
breast cancer in women 40 and older. However, it is not a perfect tool. 
Because it is not as specific a test as it could be, false positives 
can occur which often require repeat screening and/or biopsies. This 
can cause significant anxiety among patients and their families, as 
well as unnecessary health care expenditures. In addition, problems 
with mammogram interpretation and communication of results to patients 
can result in cancers that are missed and treatment that is delayed.
    As a result, the effectiveness and usefulness of mammography have 
been the subject of controversy for many years. AHRQ, along with other 
agencies of the Department of Health and Human Services, have worked to 
build the foundation of evidence for the effectiveness of mammography 
and to ensure that patients have access to high quality screening.
    One of AHRQ's earliest activities in this area was the development 
of a clinical practice guideline on how to identify the elements of 
high quality mammography screening.
    The guideline, developed in 1994 by an independent panel sponsored 
by AHRQ's predecessor, the Agency for Health Care Policy and Research, 
was entitled Quality Determinants of Mammography. The multidisciplinary 
panel that developed the guideline comprised radiologists, radiologic 
technologists, medical physicists, family practice physicians, a nurse, 
an obstetrician-gynecologist, a surgeon, a pathologist, an internist/
oncologist, and consumer representatives. Many of these panel members 
also served on the original Food and Drug Administration (FDA) National 
Mammography Quality Assurance Advisory Committee.
    The guideline provided information to clinicians on providing high 
quality mammography services and also gave patients information on how 
to determine the quality of the mammography services they received.
    It is important to note that science and research are continually 
moving forward, and that medical practice must keep pace. In 2001, AHRQ 
reviewed the guidelines it had developed in the 1990s to determine 
which were still scientifically valid. Among those found to be out of 
date was the Quality Determinants of Mammography, a guideline that was 
published in 1994 and is therefore 8 years old.
    Given the restructuring of AHRQ's guideline development activities 
in 1996, the evidence base for the guideline has not been updated since 
its initial release. A recent study sponsored by AHRQ has shown that 
the lifetime of a guideline is variable, but, generally, guidelines 
should be reviewed every 3 years
    AHRQ now makes evidence-based guidelines available through the 
National Guideline Clearinghouse (NGC), an Internet-
based compendium of more than 1,000 evidence-based clinical practice 
guidelines found at http://www.guideline.gov. At this time, the site 
contains 76 guidelines related to breast cancer and 23 related to 
mammography. AHRQ sponsors the NGC in partnership with the American 
Medical Association and the American Association of Health Plans. The 
NGC Web site provides the most current recommendations on screening 
mammography from leading guideline developers in the United States and 
around the world.
    The NGC is an internationally recognized source of high-quality, 
evidence-based clinical information. Currently, NGC has approximately 
55,000 user sessions and 950,000 hits a week. Guideline developers are 
contacted yearly to verify that their guidelines are considered 
current. After 5 years, if the developer has not reviewed its 
guideline, it is withdrawn from the site.
                        research on mammography
    AHRQ sponsors health services research that helps to inform the 
delivery and quality of health care services. The Agency has supported 
a number of important studies on the quality of mammography, its 
interpretation, and access to screening.
    A study by Craig Beam, Ph.D., of the Medical College of Virginia, 
found that U.S. radiologists looking at the same mammogram are likely 
to interpret it quite differently. In their study sample, Dr. Beam and 
his colleagues found that some radiologists referred 100 percent of 
women with cancer for biopsy, while others referred only 47 percent. 
Inaccuracy in mammogram interpretation may mean that breast cancer goes 
undetected or is detected at a later stage, when it is more difficult 
to treat successfully.
    Another AHRQ study, co-funded with the National Institutes of 
Health, is attempting to identify reasons for variability in the 
interpretation of mammograms. The study, led by Joann Elmore, M.D., at 
the University of Washington, is a unique collaboration among three 
geographically distinct breast cancer surveillance programs in the 
states of Washington, New Hampshire, and Colorado. This collaboration 
will permit the collection of breast cancer outcome and interpretive 
data on more than 500,000 mammograms from 91 facilities and 279 
radiologists.
    Dr. Elmore's study is especially timely because it takes place in 
the community setting where the majority of mammograms occur. Although 
mammography facilities are subject to rigorous accreditation standards 
regulated by the FDA, requirements do not include an evaluation of 
radiologists' accuracy levels in mammography or address the issue of 
variability in interpretation. Identifying the causes of variability of 
interpretation will be extremely important in enhancing the quality of 
screening mammography.
    The Agency also is supporting research to understand barriers to 
breast cancer screening and improve access. For example, a study funded 
by AHRQ found that negative attitudes about mammography might play a 
role in the disproportionate number of breast cancer deaths among 
African American women compared with white women. Knowledge of 
screening recommendations and access to free mammograms were not enough 
to get some low-income black women to keep their mammography 
appointments. Most of the women who skipped their appointments said 
they were embarrassed or believed that a mammogram was unnecessary if 
they didn't have any symptoms.
    Another study funded by AHRQ found that a major reason women cite 
for not undergoing breast and cervical cancer screening is that their 
physicians never recommend it. Older women, in particular, are less 
likely to be screened. This may be due in part to conflicting 
professional recommendations for screening older women, the many 
competing causes of mortality as women age, and possible negative 
attitudes about screening held by doctors and their older female 
patients.
    An important element of AHRQ's research agenda is helping to ensure 
that the research it sponsors is translated into improved clinical 
practice. The first step in this translation is the publication of 
these findings in the professional literature. The Agency also works 
with professional and patient groups to disseminate the findings to 
those who can put them to work in routine medical practice.
                 new uspstf mammography recommendation
    The debate over the usefulness of mammography has recently 
intensified. Much of this debate has focused on the critiques of the 
scientific literature on mammography screening by Olsen and Gotzche of 
the Nordic Cochrane Center in Copenhagen.
    Over the last two years, the USPSTF has been reviewing the same 
scientific literature. The findings from this review were the 
foundation of the mammography recommendations released by Secretary 
Thompson on February 21.
    Acknowledging that the scientific evidence is not perfect, but not 
as flawed as others have claimed, the USPSTF recommends screening 
mammography every 1 to 2 years for women age 40 and older. Evidence of 
benefit and reduced mortality is strongest for women aged 50-69, the 
age group generally included in screening trials.
    The evidence was unclear on when women should have their first 
mammogram and how frequently they should be screened, so the Task Force 
recommends that women should discuss their personal preferences and the 
harms and benefits of mammography with their clinicians to determine 
when to start routine screening mammography and the optimal interval 
for screening.
    AHRQ is working to get the new USPSTF recommendation translated 
into improved clinical practice and into information that will help 
reduce confusion and anxiety among patients.
    As a start, AHRQ has made the new recommendation on mammography 
available on our Web site at http://www.ahrq.gov/clinic/3rduspstf/
breastcancer/index.html. Also available are a fact sheet for clinicians 
and information for patients.
    AHRQ also will use the Put Prevention Into Practice (PPIP) program 
to help get this information out to preventive services providers and 
patients around the country. PPIP, an AHRQ program, is designed to 
increase the appropriate use of clinical preventive services, such as 
screening tests, immunizations, and counseling, which are based on 
USPSTF recommendations.
                               conclusion
    AHRQ has a tradition of supporting and conducting evidence-based 
research and translating that research into improved clinical practice. 
The Agency also has led the way in providing evidence-based information 
for health care decision making for mammography, other important 
screening tools, and other clinical issues.
    As HHS Secretary Tommy G. Thompson said on February 21, screening 
mammography can save lives. But this test is not perfect, and we need 
more research to improve the mammography and the interpretation of 
results. We also must ensure that women have the information they need 
to make decisions about their own health. Finally, it is particularly 
important that we continue periodic evaluations of the available 
scientific literature to ensure that medical practice and patient 
decision making are based on an up-to-date foundation of evidence.
    Thank you very much for the opportunity to comment on this 
important issue, and we look forward to any questions that you may 
have.
 Prepared Statement of the Food and Drug Administration, Department of 
                       Health and Human Services
                              introduction
    Madam Chairwoman, Mr. Chairman, members of the Committees, thank 
you forgiving the Food and Drug Administration (FDA or the Agency) this 
opportunity to present this statement for the record regarding 
Mammography Quality Standards Act (MQSA) of 1992.
                               background
    The MQSA of 1992 was enacted in response to serious concerns about 
the quality of mammography. This procedure is an aid in combating the 
mortality associated with the growing incidence of breast cancer. In 
spite of the current controversy about the studies showing the benefits 
of mammography screening and in the absence of consensus about the 
scientific issues, the Department of Health and Human Services (HHS) 
and FDA support the conclusion reached by the U.S. Preventive Services 
Task Force. High quality mammography continues to be the best available 
tool for the early detection of breast cancer and MQSA provides our 
best assurance of that quality.
    Mammography can reveal cancerous lesions up to 2 years before a 
woman or her doctor can feel a lump, and is a significant contributor 
to the current 5-year survival rate of 86 percent. Mammography 
represents life-saving ammunition in the war on breast cancer which is 
the most common non-skin cancer and, after lung cancer, the second 
leading cause of cancer deaths among women.
    To achieve these benefits, all elements of the mammography system 
must be of high quality. Mammography is a highly challenging 
radiographic examination of the breast. The equipment must be capable 
of producing quality images and be maintained and operated by qualified 
individuals. Physicians who interpret these images must also be highly 
skilled. If the quality of mammography is poor, an incipient cancerous 
lesion may be missed. False negative diagnoses can delay early 
treatment and result in avoidable deaths. Poor quality mammography can 
also lead to false positive diagnoses, in which normal tissue is judged 
to be abnormal, resulting in needless anxiety for patients, costly 
additional testing, and unnecessary biopsies.
    In the mid-1980s, indications of problems with the quality of 
mammography began to appear. Significant evidence came from a 1985 
study known as the Nationwide Evaluation of X-ray Trends (NEXT), which 
was conducted by State radiation control agencies in cooperation with 
the FDA. Based on a survey of a representative national sample of 
mammography facilities, this study found that the image quality 
produced in perhaps as many as one-third of the facilities was less 
than desirable.
    The findings from the NEXT study catalyzed efforts by the American 
College of Radiology (ACR), a private, non-profit association of 
radiologists, to create a voluntary mammography accreditation program. 
Begun in 1987, this program included an evaluation of the quality of 
clinical mammograms provided by facilities seeking accreditation. 
Although it is reasonable to surmise that facilities participating in 
this voluntary program were among the better facilities, ACR found that 
approximately 30 percent of the applicants failed on their first 
attempt to achieve accreditation.
    Other evidence came from a 1990 General Accounting Office (GAO) 
study that reported that many mammography providers lacked adequate 
quality assurance programs. In 1992, hearings held by the Senate 
Committee on Labor and Human Resources revealed a wide range of 
problems with mammography services in the United States. These problems 
included poor quality equipment, lack of quality assurance procedures, 
poorly trained facility personnel, and inconsistent governmental 
oversight. At the same time, several States instituted programs to 
ensure that their residents were being provided with high quality 
mammography.
    Despite these efforts, no national standards for providing safe, 
reliable, and accurate mammography were in place for the over 25 
million American women who undergo the procedure annually. To rectify 
this situation, Congress enacted the MQSA on October 27, 1992, to 
ensure uniform high standards for mammography facilities, their 
equipment and personnel, and the quality of their mammograms. This law 
required all mammography facilities be certified by the Federal 
government after October 1, 1994, except for those facilities operated 
by the Department of Veterans Affairs (DVA). A separate law mandating a 
similar program governs DVA facilities. Responsibility for implementing 
MQSA was delegated to FDA by the Secretary of HHS on June 2, 1993.
                             implementation
    Faced with the task of certifying approximately 10,000 mammography 
facilities in less than 2 years, FDA published interim regulations in 
December 1993, which became effective in February 1994. As a 
prerequisite to certification, facilities had to be accredited by an 
FDA-approved accreditation body, the first of which was ACR approved in 
March 1994. Subsequently, four States, Arkansas, California, Iowa, and 
Texas, achieved approval as accreditation bodies.
    FDA successfully met its demanding statutory deadline of certifying 
all qualified mammography facilities by October 1, 1994. While the 
interim regulations were in effect, FDA developed more exacting 
regulations, and the MQSA final regulations were published in October 
1997, and became effective on April 28, 1999.
    Another hurdle was obtaining qualified personnel to annually 
inspect the nearly 10,000 mammography facilities. FDA developed special 
training courses for both FDA and State personnel, and trained and 
eventually deployed 250 inspectors to conduct annual facility 
inspections. These inspections began in January 1995. During this time, 
FDA implemented the Mammography Program Reporting and Information 
System (MPRIS), a dynamic, interactive data system, designed to tie the 
pieces of the program together. MPRIS provides and tracks information 
on accreditation and certification of facilities, facility inspections, 
inspection violations, and the billing of inspection fees. MPRIS also 
allows inspectors to use uniform software on a laptop computer while in 
the field, and to directly upload inspection results to the 
headquarters database, thus streamlining the inspection process and 
facilitating data analysis. In addition, the database transmits daily 
certification information to the Centers for Medicare and Medicaid 
Services, thereby facilitating efficient facility reimbursement, and 
allowing consumers to search for certified mammography facilities by 
zip code.
    In order to educate facilities about the regulations and how to 
comply with them, FDA published a quarterly newsletter that was mailed 
to facilities and other interested parties. The printed newsletter 
eventually evolved into web page updates and articles on matters of 
importance to facilities. A mammography website (www.fda.gov/cdrh/
mammography) was created, a principal component of which is an 
extensive policy guidance help system.
                          developing programs
    MQSA allowed States that desired to do so to take on the role of a 
certifying body, with FDA approval and oversight. In August 1998, the 
States as Certifiers (SAC) pilot was initiated with two participating 
States. During this time, regulations were promulgated and published in 
February 2002. These regulations will become effective in May 2002. 
Several additional States have expressed interest in the SAC program, 
and FDA expects this program to expand.
                           program compliance
    Compliance with the final regulations continues to improve. 
Currently, 60 percent of all certified facilities are in total 
compliance with MQSA. The Government Performance Results Act goal for 
most serious violations is less than 3 percent. At this time, only 2.4 
percent of facilities are exceeding the goal. This exemplary compliance 
rate can in large part be attributed to the program's extensive 
outreach efforts, including facility education by inspectors, and the 
availability, both on the web and in hard copy, of all guidance and 
policy determinations.
                           program assessment
    In 1995 and 1997, the GAO evaluated aspects of the MQSA program. 
These favorable reports found that the initial impact of the new 
Federal law had been positive, while the report that looked at 
mammography inspections found that facility compliance was continuing 
to improve.
    FDA performed facility satisfaction surveys under both the interim 
and the final regulations to review how facilities perceive the 
inspection process and the program's educational and guidance 
materials. Based on these results, it is clear that the vast majority 
of facilities see the MQSA inspection program as beneficial, 
particularly the educational approach of the inspectors that helps 
facilities identify areas for improvement.
    FDA continues to fine-tune the MQSA program to better serve the 
mammography community, leading to higher quality care for the women of 
America.
                            reauthorization
    MQSA was reauthorized in October 1998, with the enactment of the 
Mammography Quality Standards Reauthorization Act (MQSRA). MQSRA 
mandated that patients be directly notified of their mammogram results, 
in lay language. The regulations were amended to reflect this mandate. 
Facilities quickly complied, and currently, there are almost no 
inspection violations in this area. In addition, a study published in 
the February 2002 American Journal of Roentgenology surveyed patients 
before and after this requirement went into effect. The study found 
that there was a substantial increase in the number of patients who 
reported timely receipt of mammography results, and a substantial 
decrease in patients dissatisfied with their results, all without an 
appreciable increase in patient anxiety.
    Congress also requested FDA to determine if best-performing 
mammography facilities can maintain their high standards without the 
scrutiny of annual inspections. With input from the conference of 
Radiation Control Program Directors, FDA designed a demonstration 
program whereby citation-free facilities from States who agreed to 
participate were randomly assigned to study and control groups. Those 
study group participants would begin skipping their next annual 
inspection, beginning in May 2002. After data collection is completed 
in the summer of 2004, data analysis will be performed and a report 
will be presented to Congress in mid-2005.
    Reauthorization of the appropriations authority for the 
Certification of Mammography Facilities would allow the Federal 
government to continue to ensure that all mammography facilities 
provide high quality mammograms as an aid in the early detection of 
breast cancer.
                               conclusion
    FDA has successfully implemented the MQSA program and has improved 
the overall quality of mammography by constructing and implementing an 
effective program that holds all providers of mammography to the same 
standard. The MQSA program in an invaluable tool in promoting public 
health and merits reauthorization.
                          Oncology Nursing Society,
                                  Pittsburg, PA 15220-2749,
                                                 February 26, 2002.
Hon. Edward M. Kennedy, 
U.S. Senate,
Washington, D.C. 20510.

Hon. Judd Gregg, 
U.S. Senate,
 Washington, D.C. 20510.
    Dear Chairman Kennedy and Ranking Member Gregg: On behalf of the 
more than 29,000 nurses and other health professionals of the Oncology 
Nursing Society (ONS), we are writing to inform you of our position on 
mammography screening for breast cancer and our concern about the 
impact of the recent report published in the British medical journal, 
The Lancet, which concluded that no scientific support exists for 
breast cancer screening with mammography. For your reference, we have 
attached the ONS position paper on mammography, a public awareness ad 
supported by ONS on this issue, and a letter to the editor of the New 
York Times signed by ONS and numerous other cancer related 
organizations voicing concern regarding the impact that The Lancet 
article could have on public health.
    ONS, the largest professional oncology group in the United States, 
exists to promote excellence in oncology nursing, teaching, research, 
administration; education in the field of oncology, and the provision 
of quality care to individuals affected by cancer. As part of our 
mission, we stand ready to work with policymakers at the local, state, 
and Federal levels to advance policies that will reduce and prevent 
suffering from cancer, including access to cancer detection tools that 
locate cancer early when both the chances of survival and treatment 
outcomes are highest.
    Breast cancer is the leading cancer and the second leading cause of 
death from cancer in women in the United States. Additionally, for 
women between the ages of 15 and 54, breast cancer is the leading cause 
of cancer-related death. Early detection of cancer, including routine 
mammography screening, has been shown to decrease a woman's chance of 
dying from breast cancer. It is the position of ONS that:
     every woman has the right to make an informed decision 
about her need for mammography screening;
     baseline mammography must occur for all women by age 40;
     screening mammography must be provided every year for all 
women ages 40 and older who are at average risk for the development of 
breast cancer;
     women at higher than average risk due to genetic or 
lifestyle factors must have access to expert medical guidance to define 
the appropriate age to begin and the frequency of mammography 
screening; and
     mammography must be included as part of routine follow-up 
care to detect the recurrence in women who have been treated for breast 
cancer.
    Although research continues to develop improved methods for early 
detection, at the present time, high-quality mammography coupled with 
adequate clinical breast exams remain the most effective means of early 
detection. ONS, like many in the cancer community, are concerned about 
the impact that The Lancet journal article will have on women's 
decision to be screened for breast cancer, that lives may be lost if 
women ultimately are dissuaded from having regular mammograms. Although 
the existing studies of mammography screening do have known limitations 
and even some flaws in design, ONS does not believe that any compelling 
evidence exists at this time that would warrant dropping the 
recommendation of mammography as a screening tool for the early 
detection of breast cancer.
    ONS maintains that public and private health insurance plans, must 
continue to provide coverage of--and access to--age and risk 
appropriate mammograpy screening for all women who seek it. ONS will 
continue to monitor the research and await review by experts of these 
studies, as well as additional research in this area. To that end, we 
are hopeful that much of the doubt recently cast upon mammography will 
dissipate in light of last week's U.S. Preventive Services Task Force 
(USPSTF) recommendation calling for screening mammography, with or 
without clinical breast examination, every one to two years for women 
ages 40 and over. In addition, last week both the National Cancer 
Institute (NCI) and the U.S. Department of Health and Human Services 
(HHS) reaffirmed their support of mammography; these statements further 
validate the value of this important cancer screening tool.
    ONS stands by its position that every woman has the right to make 
an informed decision about her need for mammography screening for the 
early detection of breast cancer. Should you have any questions or need 
more information regarding ONS' position on this important public 
health matter, please do not hesitate to contact us at (412/921-7373) 
or our Washington Health Policy Associate, Ilisa Halpern (202/857-
8968).
            Sincerely,
              Paula Trahan Rieger, RN, MSN, AOCN, CS, FAAN,
                                                         President.

                                 Pearl Moore, RN, MN, FAAN,
                                           Chief Executive Officer.
                                 ______
                                 
                Prepared Statement of Samuel B. Wallace
  mammograms detect cancer suggested new systemic & local antibiotic 
   therapy that is effective against micro breast cancer cells, thus 
  therapy was developed by samuel b. wallace, author of this research 
                                 paper
    Subject: Whether Mammograms save Breast Cancer Patient's lives? 
Distinguishing Cancer Detection and Cancer Therapy with emphasis on 
more precise Systemic and Local Therapy as I suggested in Subcommittee 
Hearings in 1979 in written testimony before Select Subcommittee on 
Cancer Research titled: ``Frontiers in Cancer Research.'' Subcommittee 
on Health, House and Senate Committees Chaired by Senator Weicker and 
Chairman Natcher, May 1985 published in 1985 and 1986. Which were 
confirmed by the Five Year Clinical Trials of Dr. Bonadonna, an NIH 
Grantee as he reported in the Journal: CANCER RESEARCH, May 1988. The 
main point of the debate on this issue suggests to me that perhaps 
there should be two categories of Doctors--a Doctor of Medicine and an 
Doctor of Surgery. One would deal with the application of curative 
medicines and the other would deal with Surgical Procedures which also 
culminate in the saving of human lives. Thus far all in the field of 
Breast Cancer with the exception of Doctor Bonadonna place the emphasis 
on drastic or minimal surgery with the area of Cancer Metastasis all 
but forgotten or ignored. Thus the real issue seems to be justifying 
surgery rather than that of treating and cuing Micro Cancer.
     mammograms only detect cancer--it is not claimed they cure it
    Proponents on both sides of the raging Debate all agree on one 
point and that is that Mammograms do detect Cancer better than any 
other medical device known to Medical Science. However, because the use 
of mammograms with concurrent Breast Cancer therapy of Surgery, 
radiation and chemotherapy does not produce a positive long lasting 
cure, the critics of the results of Cancer therapy suggest that perhaps 
mammograms should not be used because some forms of Cancer Therapy are 
not very effective. Thus, in Breast Cancer therapy for small Breast 
Cancer Tumors ``the size of pencil points there is concern that Surgery 
followed by Radiation has produced only a very small increase in 
survival. While the benefits of early detection are unquestioned for 
larger sized tumors. It should be noted that the manufacturers of the 
Mammogram do not claim that their machine has any therapeutic value but 
only that it is capable of detecting even small cancer cells at close 
to the time of the breast cancer cells inception. Therefore the real 
issue is not about the Mammograms that successfully detect even the 
smallest cancer cells in a very early stage but the therapy that 
sometimes fails in curing the Breast Cancer.
    The American Cancer Society in its 2nd Edition of Oncology 1996, 
Ch.12: Breast Cancer indicated at P. 296:

``Routine mammography (combined with good Breast Cancer Therapy) will 
    reduce Breast Cancer Morality by at least 30%. No strategy has been 
    shown to have a larger impact on breast Cancer Mortality and use of 
    such techniques has not been as well established for any other 
    disease:Day, N.E.: ``Screening for Breast Cancer. British Medical 
    Bulletin, 1991; 47: 400-415.''
Time Magazine, February 18, 2002 in its article: Rethinking Breast 
    Cancer P 50:
``Doctors know what to do when they find tumors the size of marbles--. 
    . . surgery, radiation and chemotheopy. But what to do when the 
    cancers are as (small) as pencil points? Do you treat them as 
    massive tumors or do you leave them alone? 30 years ago these small 
    tumors called ``DCIS'' were diagnosed in 6% of time. . . . Today it 
    is approximately 20% largely because of detection . . .''
    The questions asked by the writers of the February article on 
``Rethinking Breast Cancer'' (Therapy) ``do you treat small breast 
cancer tumors as you would massive tumors or do you leave them alone?'' 
is not a difficult one to answer since it is obvious from their article 
that medicine has met with some success in treating large breast 
cancers, but not small ones. The obvious answer to that question is to 
find a new way to cure small breast tumors.
    Small breast cancer tumors the size of pencil points generally 
begin in either the bone marrow and travel to the breast or begin in 
the small capillaries of the breasts that lead to the breast ducts. 
This poses a special problem for the breast Cancer Therapist. In the 
ordinary initial immune responses, the tissue macrophage and the 
smaller neutrophils in breast tissue called ``histiocytes of breast 
tissue increase and immediately injest invading Bacteria and Viruses. 
Next, the neutrophils in the blood increase as a result of a 
combination of chemical released by the infected tissue. In acute 
infection, those Immune cells can act almost instantly. But in the case 
of precursor Cancer cells their action is much slower. There is a 
combination of chemical substance released from the infected tissue 
including neutrophils which carry natural antibiotics, toxicins and 
immune hormones as well as therapeutic antibiotics which are called 
``leucosytosis'' inducing factor which diffuse from the precursor or 
tumor cells into the blood where it is transported into the Bone 
Marrow. This action also causes the circulating neutrophils carrying 
natural and man-made antibiotics to move to the targeted cancer 
infected tissue.
    However, in the case of the small capillaries \1\ which lead to the 
breast cancer ducts there are a number of barriers to the small 
capillaries which prevent the Antibiotics from being absorbed by the 
tissue and its capillaries which lead to the blood system. In addition, 
the small tumors because of their size and density of their tissue can 
not absorb the Antibiotic when it is applied directly.
---------------------------------------------------------------------------
    \1\ N.Y. Times Feb. 12, 2002 D5 shows nonspecific therapy adds 
Antibiotics to all B.M. targeted cells!
     /Id. N.Y. Times Feb. 12, 2003 Sect. D5: Showing mechanism by which 
Immune and Blood Cells are targeted to their destination by means of 
their receptors which attach to a matching receptor at a specific 
location in the nearby blood vessel which is near a specific tissue 
type such as the skin, GRR, GGH, or GTV protein cells, or the LVS, 
protein cells of the skeletal muscle which has a similar target 
receptor, such as the rib cage bones to which the Breasts are attached 
which are also linked to the arteries and veins in the Bone Marrow. It 
is important to note that many of these Immune Cells are Bone Marrow 
Macrophage which immediately ingest the Antibiotic when an Antibiotic 
is Injected into the Bones. Thus, the macrophage become essentially 
Antibiotic Macrophage which carry quantities of Antibiotics to the 
Cancer Infected area of the Breasts. See also: Nature Immunology 3, 
189, Feb. 2002 ``How GD94-NR G2A Receptors regulate T4 Cell Immune 
Response by Moser . . .; NATURE MAGAZINE, Feb. 2002, ``Reporting that 
they have identified five area receptor codes which the matching Bone 
Marrow Blood vessels.
---------------------------------------------------------------------------
    Therefore, in order to treat small sized tumors or their precursors 
they must be treated by one of two routes by means of medication 
applied to the nose that enters 85% of the patient's blood supply and 
is truly systemic in that it treats the patient's entire blood system 
and entire glandular system. For most illnesses this is good therapy 
which produces the immediate activation of complement the beginning of 
the curative process which I indicated in Testimony Samuel B. Wallace, 
before Subcommittee of Health, House Ways and Means Committee Dec. 4th, 
1975 was true for a wide variety of Viral, Bacterial and Protozoa 
Illnesses.
    When there are barriers to Antibiotic therapy, such as the Blood 
Brain Barrier, as for example in the case of encephalitis of the brain, 
a slightly different approach is necessary for the best results. And 
this is true not only for Breast Cancer but also for of all things Lung 
Cancer where ordinary large cell treatment has not worked for small 
cell lung carcinoma. In both, the Bone and Bone Marrow are it would 
seem a far better route of application of the Antibiotic such as 
Penicillin or Tetracycline. And that is because in both instances the 
bone marrow which has access to virtually all the immune cells also has 
immediate access to the small carcinoma or precursors of Breast Cancer 
or Lung Cancer through the skeletal system which directly links both 
the Breast Tissue and the Lung Tissue including the small capillaries 
in each case! And this also has to do with the particular ``Defensins'' 
or natural antibiotic which are specific in neutrophils targeted for 
specific areas and tissues of the body as explained in a splendid 
article in the American Society of Microbiology News 5:56,315-320, 
1990, the authors Robert Lehrer, Tomas Ganz and Michael Selsted, 
Professors of Medicine, (UCLA) explain @ 315: ``Researchers have found 
a variety of Peptides (naturally occurring Antibiotics in man) with 
Antibacterial, antifungal, antiviral and cytotoxic Activities'' called 
``Defensins'' or natural antibiotics.
    ``Defensins'' are ``natural peptide antibiotics from neutrophils'' 
or natural antibiotics produced by the human body to fight bacterial 
and viral infections including cancer and leukemia'' (asm) are a key to 
understanding: how the natural immune response overcomes cancer.
    In the recent past most Medical Textists while acknowledging that 
the Innate Immune System which they describe as: Antigen to Macrophage 
Activation and Macrophage to Complement Activation which in turn 
stimulates the activities of other Macrophages such as Neutrophils in 
the Innate Immune Response and the activity of NK Killer Cells and T 
Cells which kill Viruses in the acquired or Indirect response. But the 
Medical Textist do not explain the positive role of the chemotaxis role 
of Antibiotics particularly in the Innate Immune Response by the direct 
application of Antibiotics to the Macrophage which leads to the instant 
activation of Blood Serum Complement whose effects I discussed in my 
1975 Testimony demonstrating that the Alveolar Macrophage when 
Penicillin and an Immune Hormone were combined and applied as Nose 
Drops good therapeutic results were obtained that cut in half the time 
it normally takes to produce a lasting cure. This therapy normally used 
10% of the Physician's Desk reference recommended curative dosage for 
Antibiotics. And I indicated that my 1975 Congressional testimony 
applied to: Viral, Bacterial and Protozoa Illnesses.
    While I indicated in my 1985 Testimony that such Alveolar 
Macrophage Antibiotic Activation of complement could be important for 
the enhancement and protection of the entire Immune system and in order 
to produce a more ``Systemic'' form of Cancer Therapy citing the 
important Research of Umtae Kim on Metastasis. And indeed, Tonagawa won 
the Nobel Prize by discussing T Cell Acquired Immunity without 
discussing the Macrophage and Innate Immunity and the chemotaxic role 
of the Antibiotics in either form of Immunity.
    The UCLA Professors of Medicine do discuss this important point in 
their article in the American Society of Microbiology on the 
``DEFENSINS'' or ``NATURAL ANTIBIOTICS'' produced by the human body in 
the activation of the Macrophage which results in their activating 
complement, the beginning of the curative process in both the specific 
and acquired Immune Response. They also mention on page 316 of the same 
article that the same natural antibiotics have a I effect on tumors 
that have targets cells in the skeletal system and target cells in 
Cancer infected tissue: (paraphrased)
Defensins are newly defined family of broad spectrum Antibiotics found 
    in the leukocytes of humans and other mammals. . . . Human 
    neutrophils contain four principal Defensins. The four principal 
    Defensins usually account for about 80% of the Neutrophils total 
    Defensin content. The Defensins contain 30 to 50% of the total 
    protein in human neutrophil's . . . granule.''
. . . Neutrophils are made by stem cells in the bone marrow.
``Neutrophils are (also) Macrophages in the circulating blood. They are 
    (highly flexible cells that enter infected tissues in large numbers 
    (with) . . . the help of chemotactic stimuli. (Such as the 
    Antibiotics) It is estimated that the Neutrophil Defensins account 
    for as much as 7% of the protein content of the Neutrophils, 
    themselves which approximates the standard standard dosage of 
    Antibiotics. The Defensin delivery system by means of the 
    neutrophil is more sophisticated than any yet constructed by the 
    pharmaceutical industry.
    The Human Defensins HNP-I . . . exert nonspecific cytoxicity 
against various human tumor cells that, depends on active target cell 
metabolism as found in the skeletal systems or bones and in the tissue, 
glands, and blood vessels. For that reason and because the Neutrophil 
Defensins account for as much as 7% of the protein content of the 
neutrophils themselves which is approximately the standard daily dosage 
of (some) Antibiotics, the Neutrophils and other Macrophage produce an 
extraordinary impact on the Immune system, singularly where most 
viruses and Cancer, and Leukemia Precursors are normally thrown off. 
And therapeutically when man made Antibiotic and Synthetic Immune 
Hormones are applied to the Immune systems directly related to the 
specific and systemic Immune, blood, glandular and skeletal immune 
systems.
    Because as consequence of the neutrophils relation to humans immune 
system and because of the enormous impact they can exert on all immune 
systems for which they are targeted Neutrophils can be characterized as 
Macrophage that carry Antibiotics (natural or man-made) as do all 
Macrophage to all the areas of infection and inflammation caused by 
Virus, Bacteria and Protozoa including those caused by Cancer, Leukemia 
and AIDS Infections which are more in that they are also Immune 
responses that have gone wrong which have produced severe genetic 
mutations which effect the structure of the Immune and Metabolic 
systems in varying degrees.
    Injection of Antibiotics into the surface of the cranium is a Bone 
Marrow Immune System Therapy which is not only important to those 
suffering from brain damage caused by ordinary diseases but also those 
caused by tumors. And it is safer and more effective less invasive than 
any other form of therapy. Particularly, surgery or radiation which one 
must recall are both very invasive Immune suppressing procedures. And 
in the recommended Antibiotic Therapy, the Macrophage and Neutrophils 
play a key role searching for damaged or diseased brain tissue which 
when found they instantly repair.
    For example, I found in Brazil that encephalitis of the brain could 
be cured by simply Injecting Tetracycline into the cranium. On the 
other hand, at John Hopkins Hospital, the standard treatment for 
encephalitis of the Brain is removal of the diseased brain tissue which 
may result in paralysis and in some cases total disfunction of the 
brain. Therefore, a simple procedure of Injecting an Antibiotic into 
the cranium is a safe and effective therapy for Encephalitis of the 
Brain which utilizes the extraordinary properties of the Neutrophil 
Macrophage Immune Cell systems which includes their ability to find 
diseased or damaged tissue and to apply both natural and man made 
Antibiotics to that tissue when they are stimulated by the chemotaxic 
effects of the added Antibiotics to the appropriate Immune System 
affected by Disease or Infection.
    The ``chemotaxic'' effects on proteins including Immune blood cells 
causing their movement particularly in conjunction with epinephrine and 
the production of the ATP Enzyme and the release of C Amp the energy 
used to fuel cellular interactions play a critical role in the Immune 
response and cause Immune cells such as the Neutrophils or Macrophage 
to move toward the areas of Infection including areas where tumors or 
even small micro tumor precursors reside. This process is best 
understood when the event is severe inflammation which is described by 
the Physiologist Guyton in ``Human Physiology'' 1982, P.48:
``The tissue macrophage are the first line of defense against infection 
    during its first hour. Neutrophils move from the nearby Bone Marrow 
    and the circulating blood to the area of inflammation within a few 
    hours after the onset of the infection where they often increase 
    four to five fold. Which is the result of a combination of chemical 
    substances that are released from the inflamed tissues called 
    leukosytosis inducing factor. This factor diffuses from the 
    inflamed tissue into the blood and is carried into the bone marrow 
    . . . causing the release of many leukocytes, . . . especially 
    large numbers of Neutrophils that are almost immediately 
    transferred from the bone marrow storage pool into the circulating 
    blood or directly from the bone marrow by way of its blood vessels 
    to nearby targeted tissue which is inflamed.
    When there is no inflammation the same basic process though 
considerably slower is basically identical. And what is noteworthy is 
that not only antigen or disease can initiate this macrophage-
Neutrophil activation of complement, but that man made Antibiotics 
applied to macrophage can do the same thing, particularly when they are 
injected into the Bone of patients infected with cancer or leukemia.
    While the standard procedure of removal of diseased brain tissue 
may cause the patient to be completely paralyzed or in some cases no 
longer living. In addition the costs of such surgical procedures are 
enormous--costing at least twenty thousand dollars per operation while 
the extremely safe injection of the Antibiotic into the surface of the 
cranium costs pennies per injection of Antibiotics and leaves the 
patient fully functional. Thus, such diseases of the brain can be 
treated by the man-made Antibiotics applied to the surface of the 
cranium where the neutrophils bearing Natural Antibiotics or 
``Defensins'' also reside and are activated by the addition of man made 
Antibiotics causing the sensitized Neutrophil Macrophage Cells to seek 
the diseased brain tissue and to treat it effectively by causing the 
Activation of Blood Serum Complement. And given the proclivity of the 
Neutrophils and other Macrophage to seek damaged and inflamed tissue 
when stimulated, the addition of Injected Antibiotic to the bone marrow 
of the cranium could lead to good treatments for wide variety of Brain 
Damage caused Neurological diseases such as Multiple Sclerosis, 
Parkinson's Disease, Autism and Epilepsy. Direct Injection into the 
surface of the cranium is recommended.
    This then is further indication that Injecting Antibiotics into the 
Bone Marrow, also for Breast Cancer Patients and small cell Lung Cancer 
would be effective in light of the role the natural Defensin 
Antibiotics play in the Bone Marrow Immune system responses to diseases 
of the brain an excellent therapy which imitates the natural Immune 
activity of the Natural Antibiotic Defensins in the Neutrophil 
Macrophages own immune response. The anatomy of the Bone Marrow Rib 
cage which are linked to the Breast tissue by means of common arteries 
and veins as well as the linkage of the rib cage veins to the Breast 
Cancer Glands and Blood Vessels also suggests that such treatment would 
be actually enhancing the normal immune response of the Breasts to 
potential malignancies which are often defeated by the normal immune 
response in that area.
    The fact that this form of therapy has been tested in over 50 
Clinical trials against Cancer and Leukemia as reported on the Japanese 
Internet in 1999 as I suggested in 1985 is also a strong indication 
that Injection of Antibiotics into the Bone for Breast Cancer is a 
reasonable alternative to the Invasive and Mutilating Procedures of 
Radiation and Surgery. The Antibiotic therapies are not only very 
effective but are also very inexpensive and invariably would yield good 
results in treating micro sized Breast Cancer Cell and would prevent 
metastasis as does Dr. Bonadonna's Breast Cancer Clinical Trials show . 
. . Dr. Bonadonna does not suggest the mild inexpensive and effective 
Antibiotic Bone Marrow therapy, perhaps because of NIH Policy which 
favors the unsafe and largely ineffective Bone Marrow Transplant 
Program which it sponsors. Thus there are two paths through which the 
Bone Marrow enter the nearby Breast tissue: One route is the 
application of the Antibiotic nose drops that treats the entire blood 
and glandular system which pass through the Breasts. Another is by way 
of the Microphage-Antibiotic entry by Injection into the rib cage 
beneath the Breasts where arteries and veins go into the nearby Breast 
Tissue where they link with target areas in the Breast tissue. Both 
forms of Breast Cancer therapy are examples of Innate Immune Therapy.
    All three forms of Innate Macrophage Therapy also activate an 
Acquired Immune response which embraces Acquired Immunity with the 
additional benefits of sensitized T Cells activity which along with the 
Macrophage and the NK Killer Cells are capable of destroying the Breast 
Cancer Tumors and Leukemia Viruses. In addition, the sensitized T Cell 
Acquired Immunity provides long term Immunity against Breast Cancer. It 
is also important to note that the Bone Marrow Immune system like the 
Lungs is linked to the Glandular System as well as the Blood System. 
\2\ Therefore combining the systemic therapy of Penicillin Nasal 
Decongestant Nose Drops and Injection of Antibiotics into the rib cage 
proximate to the Breasts should lead to a very high cure rate for most 
forms of Breast Cancer including particularly the incipient DCIS which 
infect the Breast Ducts.
---------------------------------------------------------------------------
    \2\ Arthur Guyton's: HUMAN PHYSIOLOGY AND MECHANISM OF DISEASE, 3rd 
Edition 1982, p.56. . . .``The complement System . . . is composed of 9 
Enzymes which are normally inactive but which can be activated by 
Antigen-Antibody reactions or (Macrophage to Complement reactions) . . 
. 4. Chemotaxis (of complement): ``One or more of the complement 
products cause chemotaxis of the Neutrophils and Macrophages, thus 
enhancing the number of macrophage and neutrophils in the area of the 
infection. 5. . . Complement often attacks structure of Viruses 
neutralizing them.
     P.46: . . . Properties of Neutrophils, Macrophages and Monocytes: 
. . . The Neutrophils, Macrophage and Monocytes that mainly destroy 
invading Viruses, Bacteria and other invading infections. The 
Neutrophils can destroy Viruses even in the circulating Blood. 
Macrophage are mature monocytes which also destroy viruses.
     P.48: . . . Tissue Macrophage, . . . the Alveolar Macrophage of 
the Lungs, the microglia of the Brain immediately go to work against 
infections and are the First Line of defense against infections in the 
first hour which also respond to inflammation of tissue including the 
elevation of temperature.'' (The fact that a Nasal Decongestant 
containing epinephrine combined with the Antibiotic Penicillin (called 
aptly by the Japanese: Penicillin Diversum) can activate Complement and 
reduce fevers that are caused by virus or bacteria with seconds of the 
Application of the Nose Drops is of great medical significance as I 
indicated in Congressional Testimony Dec. 4, 1975.) Also in the initial 
Immune response many neutrophils go from the Bone into the Circulating 
Blood and from thence to the Infected Tissue carrying Defensin 
Antibiotics.
---------------------------------------------------------------------------
  economic impact of this innate antibiotic therapy for breast cancer
    Those Professors of medicine are to be praised not for discussing a 
``new discovery'' in medicine, but for their courage, candor and 
honesty in discussing a fact known to science and the entire American 
and European Pharmaceutical Industry since the early 1970's when Dr. 
Hamao Umezawa, Md. And Professor of Medicine Tokyo University indicated 
in the Japanese Journal of Antibiotics 1977: 30 (Supp.):138-63 in an 
extensive article titled: ``Recent Advances in bioactive microbial 
secondary metabolites'' that he had discovered ``secondary derivative 
antibiotics'' made in the human body by a process of screening human 
blood. A simple process used now by the American and European 
Pharmaceutical Companies in which Human Blood, Animal and Fish Blood 
and even plants, animals, and earth are screened by simple centrifugal 
force, which separates the samples according to their molecular 
weights.
    What makes this method for Discovery of new Antibiotics produced by 
man, animals, fish and plants important to mankind is that it is 
extremely simple and extremely inexpensive to do as compared to the 
elaborate and costly procedures for discovery of Antibiotics by means 
of Enzyme or Protease Inhibitors a process used by Dr. Hamao, Umezawa 
to discover hundreds of Antibiotics that cure Cancer and Leukemia such 
as Bleomycin a beta lactam (penicillin) compound discussed by the NIH's 
Dr. Chabner as Editor of Oncology: Goodman's and Gilman's Pharmacology 
1996 Edition. And why was the article by Professor Lehrer et al. of 
UCLA based on a lecture he gave in Houston, Texas in 1989 so 
significant? Because the NIH to this very day in the year 2002 still 
claims that the Antibiotics are incapable of Curing Viruses from the 
simple Asthma Virus to HIV I and III Leukemia! Despite Goodman's 
Pharmacology 2nd Ed. on page 1388 it authors indicating they do. Which 
adds immensely to the cost of government and private health program's. 
The NIH in taking the unscientific policy position that the Antibiotics 
(natural or man-made) are not Antiviral Agents despite the American 
Cancer Society and generally AMA doctors success in curing virally 
caused Cancer using hundreds of Antibiotics also contradicts a medical 
text that it authored in 1955: Goodman and Gilman's. ``The 
Pharmacological Basis for Therapeutics'', 2nd Edition which on page 
1346-1347 indicated that the Antibiotic Penicillin combined with a 
Nasal Congestant Nose Drops was a Cure for Asthma. Which I confirmed in 
Congressional Testimony before the Subcommittee of Health of the House 
Ways and Means Committee, Dec. 4th, 1975 before then Congressman 
Rostenkowski of Illinois. The result of the NIH's nonscientific policy 
is that today people who are infected with the Asthma rhino virus are 
given Antiviral Asthma Agents that cost $5,000 to $10,000 per year 
until they finally succumb to Asthma virus infection. Which means in 
Government Programs the Federal Treasury looses Billions of dollars 
annually and many patient's die from Asthma and other viral illnesses 
that can not be cured by means of the NIH's Antiviral Agents which the 
NIH admits can not cure Viral Illnesses. The UCLA Professors medicine 
who in their 1990 article published in the ASM News had showed great 
courage showing that the human body produces natural antibiotics which 
cure viruses. A finding similar to my own as I had indicated based on 
my own empirical tests in Brazil from 1969 to 1974 that man-made 
Antibiotics cure a wide range of ordinary viral illnesses in a shorter 
period of time using ten percent of the PDR required curative dosage 
which I reported in my Congressional Testimony Dec. 4th, 1975. I 
informed members of Congress and former Secretary of HH&S Ms. Shalala 
that the Antibiotics cure HIV I and III Leukemia in the 1980's and 
1990's. I participated in two FDA Conferences of Physicians sponsored 
by David Kessler where I discussed the same Issues. And at an informal 
gathering on Capitol Hill I briefly discussed the Antibiotics 
effectiveness at an AIDS Conference in which Dr. Fauci was one of the 
officials present on stage.
  the economic impact of using safe and effective antibiotic therapies
    The economic impact to this approach to medicine is very positive. 
For Puerto Rico as was pointed out by a Ms. Pagan in Health Care and 
Financing Review/Summer 1983, Vol. 4, No.4: the Puerto Rican Public 
Health System is at least 95% more efficient than the stateside 
American Public Health System, (which I have personally experienced 
while teaching in Puerto Rico) because the Public Health System of 
Puerto Rico relies more heavily on Antibiotics.
    This is similar to the experience of the Japanese, Canadians and 
Hawaiian Health Systems all of whom rely more heavily on Antibiotic 
Therapy which produce far more cures. Which leads me to believe that 
some thought should be given to directing medical studies to Medicines, 
only. Thus, a doctor could be a doctor of medicine or a doctor of 
Surgery. The Medical doctor's Education would emphasize the roll of 
medicines and the human immune response through the studies of Pharmacy 
and Immunology and Biochemistry. And would be for six years rather than 
twelve. Thereby reducing the cost of Medical School by 50%. While 
surgery would emphasize gross anatomy and physiology, surgical 
procedures and why it is important to treat surgical wounds immediately 
after surgery with antibiotics as well as always finding new techniques 
for the delivery of Antibiotics for the delivery of Antibiotics to 
various areas of the human body even when those techniques sometimes 
required minor surgery. This division of Medicine into two separate 
categories: ``Doctor of Medicine and Doctor Of Surgery'' would be more 
appropriate--so that more medicine oriented procedures could be 
developed through Biochemistry, Pharmacology, Immunology and Physiology 
for Doctors of Medicine. Which would lower the costs of both who would 
be required to study the essentials of the Medical Science and 
Pharmacy. At the same time those training to be Surgeons would also 
have their curriculum shortened because they would not have to be quite 
so knowledgeable about Medicine. Both disciplines would place emphasis 
on finding the cure of illnesses rather than on long esoteric studies 
attempting always to find the cause of disease. And those studying 
Medical Science only would have fully interrelated Science courses that 
related their individual science courses to Medicine as a whole.
best innate ``systemic'' curative therapy: antibiotic decongestant nose 
                                 drops
    Ordinarily Injection of Antibiotics into the veins is considered 
sound ``Systemic'' Therapy. However, that form of Therapy treats the 
Immune System through Veinular Blood System neglecting the glandular 
system. It is significant, that Penicillin and Tetracycline Nasal 
Decongestant Nose Drops That I Rediscovered in Brazil in 1969 or 1970 
whose effectiveness against Bacteria, Viruses etc. I reported in 
Testimony before the Subcommittee on Health of the House Ways and Means 
Committee Dec. 4, 1975 is probably the best Curative Therapy for HIV I 
and III because I proved that a very wide range of illnesses were cured 
in a far shorter period of time with ten percent of the PDR's 
recommended Curative Dosage as well as Goodman and Gilman's: The 
Pharmacological Basis of Therapeutics 1955-1958 Edition, P. 1346-47: 
``A Cure for Asthma: Penicillin and a Nasal Decongestant'' as well as 
the Spanish Pharmacopoeia 1993 edition: ``Nasal Decongestant Cures 
Respiratory Illnesses'' indicates that such Therapy is the most 
effective ``systemic'' therapy for a wide range of Viral and Bacterial 
Illnesses. And should always be used in ``Systemic'' Therapy for all 
forms of Cancer and Leukemia. That application of Antibiotic Nose Drops 
is the best form of ``Systemic'' Therapy is also shown because:

(1) Application of the Antibiotic Nose Drops treats the entire 
    Glandular system to which the Lungs are attached as well as the 
    entire Blood system through which Blood passes through the Lungs 
    through the heart. That form of treatment is truly ``Systemic'' in 
    that it enters into all the systems of the Immune System.
(2) This is also proven by empirical evidence because as is indicated 
    in the Spanish Pharmacopoeia 1993: ``A Nasal Decongestant Nose 
    Drops combined with Penicillin Cures Respiratory Infections.''
(3) My Empirical tests in Brazil indicate that it cures a wide range of 
    Bacterial and Viral Illnesses. And that it reduces severe bacterial 
    and viral fevers soon after it is applied as Nose Drops. This same 
    form of therapy generally uses only ten percent of the normal 
    initial curative dosage as recommended by the PDR which is 500 mg 
    Penicillin for the treatment of Pneumonia, for example. The Nose 
    Drops produce the same effect with only 50 mg of Penicillin, which 
    begins the curative process immediately activating Blood Serum 
    Complement, which is proved by its ability to reduce fevers as soon 
    as it is applied as nose drops.
(4) Adriamycin has been designated by the American Cancer Society as 
    the most effective Anti-cancer and Leukemia Agent, the Japanese 
    Pharmaceutical Industry proved in Chemical Abstracts April 15, 1985 
    that PD-3; Penicillin Diversum combining synthetic epinephrine--
    Naphazoline Hcl in weak solution with Penicillin was 98% effective 
    against Bone Cancer in vitro, the highest rating ever given an 
    Anticancer Antibiotic in vitro.
(5) Other forms of Cancer such as Breast Cancer have been cured with 
    the common Antibiotics such as Penicillin, Adriamycin and Bleomycin 
    (a Penicillin complex compound)
(6) The Antibiotic Nasal Decongestant Nose Drops also act as an Amazing 
    Immunological growth factor that can cause the Immature Stem Cells 
    that proliferate in Leukemia Patients to begin growing once more 
    which reverses the Leukemia proliferation process.
    No other form of Systemic Therapy uses smaller quantities of 
Antibiotic to produce Cures in much shorter periods of time. See 
Testimony Samuel B. Wallace, Subcommittee of Health of the House Ways 
and Means Committee, Dec. 4th, 1975. Therefore, it is the best 
``Systemic'' therapy for Breast Cancer, Bone Cancer and Leukemia is the 
application of the Antibiotic Nasal Decongestant Nose Drops which 
treats the Lung Immune System, the most powerful Immune System in the 
human body because it is directly linked to both the Blood and 
Glandular Systems. This is confirmed by a prestigious Cancer Research 
Institute in Japan as well as by NIH Grantee Dr. Bonadonna's five year 
Clinical Studies for Breast Cancer,\2\ which has produced Cure Rates as 
high as 80% for Breast Cancer.
 injection of antibiotics into the bones is the best ``local'' (local--
                      systemic) antibiotic therapy
    In 1985, this author proposed an alternative to treating the Bone 
Marrow with medicines that were both safe and effective--namely, by 
Injecting Antibiotics into the Bone in my Testimony given before the 
Subcommittees on Health of the House and Senate Appropriations 
Committee May 1985. In that Testimony indicated that all forms of 
Cancer should be treated ``Systemically'' and ``Locally'' with the 
Curative Antibiotics and that the Antibiotics should be Injected into 
the bones of Cancer Patients in order to thoroughly treat such Patients 
and in order to prevent future reoccurrence and metastasis, citing the 
ten year work of Dr. Umtae Kim of the Rosewell Institute, Buffalo, N.Y. 
Injection of Antibiotics into the bone is the safest way to Administer 
Antibiotics and can even be given to new-borns before their veins are 
fully matured. My own research indicates that Injection of Antibiotics 
into the Bones, thus treating the bone Marrow Immune System is second 
only to the Nasal Decongestant Nose Drops in effectiveness. Thus, such 
treatment reduces a fever within approximately an hours time, while the 
Antibiotic Nasal Decongestant Nose Drops reduces the fever shortly 
after it is applied. Clinical Studies by Japanese Oncologists have 
proven that Injection of Antibiotics into the Bone is a very powerful 
and effective form of Cancer and Leukemia Therapy because there were in 
1999 50 Clinical Trials where Injection of Antibiotics were given in 
the Treatment of Cancer and Leukemia. Therefore it would seem logical 
that this safe and effective Cancer and Leukemia Therapy would also 
prove effective against HIV III AIDS Leukemia which resides in the Bone 
Marrow as well of course in the Lymph Nodes, Blood and Glands. 
Therefore, the Best Form of Antibiotic ``Local'' Curative therapy for 
HIV III Patients is Injection into the four limbs and the surface of 
the cranium, as well as injection into the AIDS Patient's Lymph Nodes 
because:
(1) It is in the Bone Marrow that Immune Cells normally grow and where 
    obviously HIV Leukemia suppresses the growth of normal immune cells 
    including the B, T and Macrophages and particularly the T4 Immune 
    Cells which play an important role in the Regulation of the Immune 
    Cells in the Immediate Immune Response as well as influencing the 
    role of the circulatory Lymphocytes. (Susumi Tonegawa the Noble 
    Laureate emphasized that without the T Cells even in the case B 
    Cell and macrophage complement activity that those responses 
    without the T Cell participation would fail. (See Scientific 
    American, October 1985, Tonegawa on the Molecular activity of the 
    Immune Cells, Page 128. Therefore Injection of Antibiotics into the 
    Bone treats the HIV AIDS Infection in its locus.
(2) The Bone Marrow Immune System is the second only to the Lung Immune 
    System in its power to begin the Immune Response and then effecting 
    a Positive result, which is a Cure. For example, applying a Nasal 
    Decongestant Antibiotic as Nose Drops to the Lung Immune System 
    initiates the Curative Process immediately as is shown by its 
    ability to reduce Bacterial and Viral Fevers which is accomplished 
    almost immediately. Reduction of Fevers by Injection into the Bones 
    is accomplished within one or two hours far shorter times than is 
    normal which generally takes four to six hours. See the Medical 
    Physiologist, Arthur Guyton.
(3) Injection of Antibiotics into the Bone thus Treating the Bone 
    Marrow Immune System has proven to be one of the most effective 
    ways to Treat and Cure various forms of Cancer and Leukemia. See 
    Japanese Internet 1999 showing 50 Clinical Trials where Antibiotics 
    cured various forms of Cancer and Leukemia.
    In May 1988, Dr. Bonadonna, a Surgeon at Instituto Tumari, Milan, 
Italy and also an NIH Grantee indicated in Cancer Research May 1988 
Treating Breast Cancer ``Systemically'' and ``Locally'', produced over 
a five year period higher Cure Rates than with Surgery or Radiation. 
That modality of Breast Cancer Antibiotic Therapy has produced Cure 
Rates as high as 80% but has not been applied to other forms of Cancer 
and Leukemia by the NIH.\2\
 the existence of defensins in the human body manufactured by myeloid 
 precursor cells in the bone marrow is significant for several reasons
    The existence of Natural Human Antibiotics which are produced by 
myeloid precursor cells residing in the bone marrow and stored in the 
cytoplasm granules of mature cells that are capable of destroying 
bacteria and viruses is significant for several reasons:
    First it destroys a fundamental fallacy where the NIH contradicted 
its own Text Goodman & Gilman's Pharmacology 2nd Ed. 1955-1958, 
Pharmaceutical Conferences in 1940 to 1950 and Armed Forces Records 
WWII and the American Cancer Society's and Japanese Doctors success in 
treating and curing Cancer and Leukemia Viruses with the Antibiotics. 
This contradictory conduct by the NIH is the basis for its reliance on 
ineffective and unsafe Antiviral Agents which have displaced low cost 
Safe and Effective Antibiotic Medicines that have long cured HIV I and 
sometimes HIV III Leukemia. This NIH fallacy has resulted in the World-
wide AIDS Epidemic which has been characterized as Security Issue by 
the United Nations and may have resulted in the infection of more than 
100 Million human beings.
    Second, the displacement of the low cost safe and effective 
Antibiotic Medicines by the NIH's Unsafe and ineffective nostrums has 
resulted in the rise in the cost of Medicines from 5,000 fold to 20,000 
fold and has produced many new categories of formally curable illnesses 
being reclassified as incurable. i.e. Asthma.
    Third, the failure to make available synthetic Antibiotic Medicines 
has resulted in unnecessary loss of human life. And now animal life 
with the wholesale destruction of livestock caused by fear of infected 
animals who are now not given precautionary Antibiotics.
 the discovery of tumoricidal alveolar (lung) macrophage & neutrophils 
which carry ``defensins'' or natural antibiotics indicate immune cells 
 combined with antibiotics can cure cancer, leukemia and hiv i and iii
    This author during the years 1970-1974 by his use of Innate 
Antibiotic Therapy (activation of Macrophage Direct activation of 
Complement) in Brazil discovered and described the effects of 
Antibiotic carrying Macrophage and Neutrophils activity in the Innate 
Immune Response. Which I describe in the Testimony of Samuel B. 
Wallace, Subcommittee of Health of the House Ways and Means Committee 
Dec. 4th, 1975, the effects of Antibiotic Macrophage and Neutrophil 
carrying Natural Antibiotics (Defensins). ``The Antibiotic Nasal 
Decongestant Nose Drops'' can:
1. Reduce Fevers to Normal Level: Viral, Bacterial and Protozoa Fevers 
    instantaneously. Since, only the Macrophage can act instantaneously 
    and the curative process begins with the activation of complement), 
    the reduction of fever is an indication that the curative process 
    has begun which is a sure indication that serum complement has been 
    activated instantaneously.
2. Can cure most Viral and Bacterial Illnesses in three days time. The 
    more difficult illnesses can be cured in a third less time.
3. Curative dosage required to begin the curative process by activation 
    of Complement is ten percent of the dosage recommended by THE 
    PHYSICIANS DESK REFERENCE. For example PDR, recommends 500 mg 
    Penicillin for Pneumonia, but using the Antibiotic Nose Drops the 
    amount of medication required is ten percent of PDR recommendation 
    or less than 5 mg per nose drop dosage.
4. Can cure most Virus, Bacteria or Protozoa Illness is a strong 
    indication of a major break through in Medical Science. The 
    discovery or rediscovery of an almost resistance free Curative 
    therapeutic.
    The four effects of the Innate Antibiotic Therapy: Immediate 
reduction of Viral, Bacterial and Protozoa, Fevers, the ability to cure 
most Viral, Bacterial and Protozoa Illnesses in three days, smaller 
curative dosages of Antibiotics which have the same effect as larger 
recommended dosages, and a medicine that can cure most illnesses is a 
very strong indication of better utilization of the patient's immune 
system and better placement of the medication in that immune system in 
achieving cures in a shorter period of time. And since only the 
Macrophage the predominant Immune System can act so swiftly to get 
natural and made Antibiotic to the locus of the Infection and beginning 
the curative process through the activation of complement. All of this 
is strong indication of a Direct Response of the Innate Immune system 
which is Macrophage to Direct activation of complement. Which begins 
the Curative Process.
    On the other hand, the experiments of Kazuyoshi Imaizumi, N. 
Hasegawa et al. who found that stimulation of the Aleveolar Macrophage 
and Antigen Presenting Cells through the CD40 and CD40L complement 
receptors which expressed tumor cells could enhance the cytotoxic 
effect of macrophages and the Antitumor Immunity of the T Cells by 
using alfa Interferon Leukosyte fragments to stimulate Macrophage 
Antitumor activity against Lung Cancer cells were inconclusive and 
ambiguous.\3\ Example: (Tested Macrophage prestimulated with 
Penicillin!)
---------------------------------------------------------------------------
    \3\ See GAN TO KAGAKU RYOHO 2000 July; 27(8): p. 1191-2000: ``Tumor 
microcirculation and selective enhancement of drug delivery-clinical 
applications.'' Dept. of Internal Medicine, Sendai Shakaihoken Hospital 
. . . using Yoshida Sarcoma (Bone Marrow Cancer Tumors) functional 
differences in microcirculation between tumor (tissues) and normal 
tissues were found by Suzuki et al. in (1977'' . . .'' It is very 
important after chemotherapy to understand . . . the pathohistological 
changes in tumor(s) and (their) . . . repaired tissues, which present 
various clinical images.'' (Whether those ``Clinical Images'' have an 
effect on Mammographic Images is an open question that I would assume 
depends to some extent upon the degree of Tumor tissue density.) . . . 
In conclusion: ``IHC (continuous infusion of Angiotensin II `increased 
tumor blood flow') might be applied to all kinds of tumors to 
(including of course small cell Breast Tumors) to enhance the 
chemotherapeutic effects through selective increase of drug delivery to 
tumors.''
     This study at Sendai Hospital Japan was devoted to Cancer Tumor in 
general, and did not refer specifically to small Cell Breast Cancer or 
small Cell Lung Cancer. But it did note that there was a great 
difference in normal tissue and tissue that was infected with Cancer 
Tumors. And that differences in tissue made a difference in the 
effectiveness of the delivery of drugs to the area of tumor infection. 
It does therefore at least support my theory which was proven with 
respect to encephalitis of the brain that there are barriers to the 
delivery of medicines to tissue, such as the well known ``Blood-Brain 
Barrier'' and I believe the small capillaries of the Breast as well as 
the circulatory barriers to the Lungs. Which helps to explain why 
doctors have not met with success in treating Small Cell Breast Cancer 
or Small Cell Lung Cancer. The following three Papers borrowed from my 
own work on another Leukemia topic, I suggest from my own empirical 
studies in Brazil from 1969 prove the importance of the routes of 
Antibiotic Delivery in treating Cancer Tumors as well as the more 
common infections and neurological diseases titled:

    BEST INNATE SYSTEMIC CURATIVE THERAPY ANTIBIOTIC DECONGESTANT NOSE 
DROPS
    INJECTION ANTIBIOTICS INTO BONES BEST LOCAL (&SYSTEMIC) ANTIBIOTIC 
THERAPY
    THE EXISTENCE OF DEFENSINS IN BODY MADE BY . . . PRECURSOR CELLS IN 
BONE MARROW IS SIGNIFICANT FOR SEVERAL REASONS

     This author, Samuel B. Wallace has enclosed those three pages 
based on his Research in Brazil 1969 to 1974 because he believes they 
may be helpful in developing new methods for the delivery of Antibiotic 
Medicines in Breast Cancer and Cancer and Leukemia Therapy. All three 
pages have been tested by Samuel B. Wallace, in Brazil.
---------------------------------------------------------------------------
    The effectiveness of the Innate Macrophage Immune Therapy: 
Macrophage to direct activation of complement and its immediate 
therapeutic effects is better tested against actual disease than 
against some remotely connected Antigen such as an Antibody or 
leucocyte particle. Which demonstrates far more effectively the ability 
of the Macrophage or other Immune Cells to act against Virus or 
Bacteria. And a better understanding of the effectiveness of an 
Antibiotic Therapy is better determined by the length of time that red 
blood serum complement is activated by the Macrophage which in turn has 
been activated by an Antibiotic or an Antibiotic combined with an 
Immune Hormone.
    A more effective laboratory test of the Macrophage's ability can be 
determined by the number of new Antibiotics found in the Macrophage 
both natural (Defensins) and man-made after the Macrophage have 
activated Blood Serum complement.
    Therefore, even though showing ``stimulating the Alveolar 
Macrophage through its CD40 and CD40L Complement Receptors'' is of 
great significance, it is of even more significance to demonstrate that 
an Immune Cell actually reacts to a specific disease by producing new 
natural antibiotics or Defensins to fight the disease. Or that it acts 
in general against a wide range of diseases of one type or another. 
Kazuyoshi et al. did use tumor cells in their experiment, but not 
Antibiotics in sufficient strength to strongly exhibit a tumoricidal 
effect! No curative dose! They, did not show Antibiotic to Macrophage: 
direct and instant activation of complement shown by the immediate 
reduction of fevers, and the cure of an extremely wide variety of 
bacterial, viral and protozoa illnesses in 1970 to 1974 for which many 
U.S. Pharmaceutical companies are today allegedly seeking to find a 
cure. And which led the Japanese Pharmaceutical Industry to dub this 
author's rediscovery ``. . . Penicilium Diversum'' Chem. Abstr,. April 
15, 1985 and as being 98% effective against the deadly sarcoma 
``yoshida sarcoma'' or bone marrow Cancer, is of more value to Medical 
science than the dubious discovery that an esoteric cellular immunity 
or acquired immunity fragment from a T cell Leukocyte Fragment also 
called ``alfa interferon'' has some impact on the macrophage because it 
means that ``researchers'' had failed to take into account the 
Macrophage's ability to do its most important work, its ability to 
Directly Activate red blood serum complement as well as its ability to 
reduce Viral Fevers and to achieve cure rates better than 90%, even 
though they nibbled around the edges of this discovery by proving that 
the Macrophage have Antitumoricidal properties by testing the 
Macrophages' Complement Receptors.
    A better more Scientific approach would have been to test the 
complement receptors against some disease or virus said to be incurable 
such as Asthma or HIV AIDS using their approach or mine which consists 
of the Antibiotic stimulating the Alveolar Macrophages' Complement 
Receptors by showing that that approach actually activates red blood 
cell complement, thus beginning the Curative Process. The use of very 
weak or dubious indicators such as Interferon or Interleukin II-12 is 
of very little significance because those indicators, themselves, only 
produce cure rates of 5% or slightly better, while Antibiotics such as 
Penicillin or tetracycline alone or combined with synthetic Immune 
Hormones such as synthetic epernephrine produce cure rates against the 
same viruses. And the question remains that an experiment that uses a 
stronger stimulant the Antibiotics to ``preserve'' the Macrophage in 
culture, whether such ``preservation'' may have prestimulated the 
Macrophage before the test of the Macrophage's by means of weak CD-40 
receptors and weak Interferon and Interleuken 2. Thus, invalidating the 
entire experiment.

    [Whereupon, at 5:10 p.m., the joint hearing was concluded.]

                                    

      
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