[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
U.S. GOVERNMENT PRINTING OFFICE
78-085 WASHINGTON : 2002
_____________________________________________________________________________
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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
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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.
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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!)
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\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.]