[Senate Hearing 105-561]
[From the U.S. Government Publishing Office]


                                                        S. Hrg. 105-561
 
                      TAMOXIFEN AND BREAST CANCER

=======================================================================

                                HEARING

                                before a

                          SUBCOMMITTEE OF THE

            COMMITTEE ON APPROPRIATIONS UNITED STATES SENATE

                       ONE HUNDRED FIFTH CONGRESS

                             SECOND SESSION

                               __________

                            SPECIAL HEARING

                               __________

         Printed for the use of the Committee on Appropriations


 Available via the World Wide Web: http://www.access.gpo.gov/congress/
                                 senate

                                 ______


                    U.S. GOVERNMENT PRINTING OFFICE
49-671 cc                   WASHINGTON : 1998


_______________________________________________________________________
            For sale by the U.S. Government Printing Office
Superintendent of Documents, Congressional Sales Office, Washington, DC 
                                 20402
                           ISBN 0-16-057288-6






                      COMMITTEE ON APPROPRIATIONS

                     TED STEVENS, Alaska, Chairman
THAD COCHRAN, Mississippi            ROBERT C. BYRD, West Virginia
ARLEN SPECTER, Pennsylvania          DANIEL K. INOUYE, Hawaii
PETE V. DOMENICI, New Mexico         ERNEST F. HOLLINGS, South Carolina
CHRISTOPHER S. BOND, Missouri        PATRICK J. LEAHY, Vermont
SLADE GORTON, Washington             DALE BUMPERS, Arkansas
MITCH McCONNELL, Kentucky            FRANK R. LAUTENBERG, New Jersey
CONRAD BURNS, Montana                TOM HARKIN, Iowa
RICHARD C. SHELBY, Alabama           BARBARA A. MIKULSKI, Maryland
JUDD GREGG, New Hampshire            HARRY REID, Nevada
ROBERT F. BENNETT, Utah              HERB KOHL, Wisconsin
BEN NIGHTHORSE CAMPBELL, Colorado    PATTY MURRAY, Washington
LARRY CRAIG, Idaho                   BYRON DORGAN, North Dakota
LAUCH FAIRCLOTH, North Carolina      BARBARA BOXER, California
KAY BAILEY HUTCHISON, Texas
                   Steven J. Cortese, Staff Director
                 Lisa Sutherland, Deputy Staff Director
               James H. English, Minority Staff Director
                                 ------                                

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

                 ARLEN SPECTER, Pennsylvania, Chairman
THAD COCHRAN, Mississippi            TOM HARKIN, Iowa
SLADE GORTON, Washington             ERNEST F. HOLLINGS, South Carolina
CHRISTOPHER S. BOND, Missouri        DANIEL K. INOUYE, Hawaii
JUDD GREGG, New Hampshire            DALE BUMPERS, Arkansas
LAUCH FAIRCLOTH, North Carolina      HARRY REID, Nevada
LARRY E. CRAIG, Idaho                HERB KOHL, Wisconsin
KAY BAILEY HUTCHISON, Texas          PATTY MURRAY, Washington
TED STEVENS, Alaska                  ROBERT C. BYRD, West Virginia
  (Ex officio)                         (Ex officio)
                      Majority Professional Staff
                            Bettilou Taylor

                      Minority Professional Staff
                              Marsha Simon

                         Administrative Support
                              Jim Sourwine


                            C O N T E N T S

                              ----------                              
                                                                   Page
Opening remarks of Senator Arlen Specter.........................     1
Opening remarks of Senator Lauch Faircloth.......................     2
Statement of Dr. Harold Varmus, Director, National Institutes of 
  Health, Department of Health and Human Services................     3
Statement of Dr. Norman Wolmark, chairman, National Surgical 
  Adjuvant Breast and Bowel Project [NSABP] breast cancer 
  prevention trial...............................................     4
    Prepared statement...........................................     6
Tamoxifen and raloxifene.........................................     8
Statement of Dr. Richard D. Klausner, Director, National Cancer 
  Institute, Department of Health and Human Services.............     9
    Prepared statement...........................................    10
High risk category...............................................    12
Statement of Helene Wilson, participant, National Surgical 
  Adjuvant Breast and Bowel Project [NSABP] breast cancer 
  prevention trial...............................................    13
    Prepared statement...........................................    16
Clinical trials..................................................    37
Statement of Cynthia Pearson, executive director, National 
  Women's Health Network.........................................    37
    Prepared statement...........................................    39
Tamoxifen........................................................    41
Defining high risk category......................................    42
Raloxifene and tamoxifen.........................................    44
Statement of Dr. Bernard Fisher, chairman and principal 
  investigator, National Surgical Adjuvant Breast and Bowel 
  Project........................................................    46
  


                      TAMOXIFEN AND BREAST CANCER

                              ----------                              


                        TUESDAY, APRIL 21, 1998

                           U.S. Senate,    
    Subcommittee on Labor, Health and Human
     Services, and Education, and Related Agencies,
                               Committee on Appropriations,
                                                    Washington, DC.
    The subcommittee met at 1:40 p.m., in room SD-192, Dirksen 
Senate Office Building, Hon. Arlen Specter (chairman) 
presiding.
    Present: Senators Specter and Faircloth.

                DEPARTMENT OF HEALTH AND HUMAN SERVICES

                     National Institutes of Health

STATEMENTS OF:
        DR. HAROLD VARMUS, DIRECTOR, NATIONAL INSTITUTES OF HEALTH
        DR. RICHARD D. KLAUSNER, DIRECTOR, NATIONAL CANCER INSTITUTE

                       NONDEPARTMENTAL WITNESSES

STATEMENTS OF:
        DR. NORMAN WOLMARK, CHAIRMAN, NATIONAL SURGICAL ADJUVANT BREAST 
            AND BOWEL PROJECT
        HELENE WILSON, PARTICIPANT, NATIONAL SURGICAL ADJUVANT BREAST 
            AND BOWEL PROJECT, BREAST CANCER PREVENTION TRIAL
        CYNTHIA PEARSON, EXECUTIVE DIRECTOR, NATIONAL WOMEN'S HEALTH 
            NETWORK
        DR. BERNARD FISHER, CHAIRMAN AND PRINCIPAL INVESTIGATOR, 
            NATIONAL SURGICAL ADJUVANT BREAST AND BOWEL PROJECT

                   opening remarks of senator specter

    Senator Specter. The hearing of the Subcommittee on Labor, 
Health and Human Services, and Education will now proceed.
    We very much appreciate this distinguished group coming in 
today. We have Dr. Harold Varmus, head of NIH, Dr. Richard 
Klausner, head of the NCI, and our distinguished panelists, Ms. 
Cindy Pearson, Ms. Helen Wilson, and Dr. Norman Wolmark.
    We have convened this hearing in order to examine the 
progress which has been made on tamoxifen. The very remarkable 
news was released recently about a single pill a day having 
very dramatic results for women who are at high risk for 
cancer. Just yesterday, the information came out about 
raloxifene and the tremendous strides which that pill has given 
with lesser side effects. There is a great concern publicly 
about what the import of these two pills are, where we are 
heading on further studies, where we are heading on further 
announcements.
    I know there is to be some official statement made in the 
near future and we are in the midst, at this moment, of 
considering the budget for the National Institutes of Health. 
It is always controversial as to whether we are going to get 
the kind of funding we are looking for.
    It seems to me at this particular time, with the budget 
very much under consideration and with so much public interest 
in these two pills, that it would be very useful to have this 
hearing.
    There has been much said about dramatic increases in 
funding for NIH. But, Congress has not been quite so ready to 
appropriate the funds.
    Last year, we had a sense-of-the-Senate resolution to 
double NIH funding in 5 years. Then, when last year's budget 
came down, the health account was $100 million short.
    Senator Harkin and I joined together to offer an amendment 
to add $1.1 billion, an across the board cut, which was 
defeated 63 to 37. This year, again the accounts for this 
subcommittee were frozen.
    Although some may make calculations about an increase in 
NIH funding, it would have to come out of the other vest 
pocket, so it is not there. Again, Senator Harkin and I offered 
an amendment this time to increase NIH funding by $2 billion, 
which is still short of doubling in 5 years. It would take 
about $2.7 billion to do that.
    Again, that amendment was defeated on the Senate floor 2 
weeks ago Thursday when we finished up on our budget 
considerations.
    We have been successful in having very significant 
increases in cancer funding--from fiscal year 1995, $2.13 
billion; 1996, $2.25 billion; 1997, $2.39 billion; and 1998, 
$2.55 billion. We were successful last year in finding some 
$907 million after conference. We had $952 million in the 
Senate mark. We are trying to project ahead this year for even 
more funding.
    It is a question as to whether the increases in funding 
have led us to the remarkable progress on these two pills and 
whether additional funding would produce even more.
    Although many grants are being awarded, the number is 28 
percent. There are still many doors which are unopened as to 
what those research applications would bring.
    For those reasons, we are very pleased to be able to 
proceed at this relatively early moment to have what I consider 
to be a very important hearing.
    I am delighted to yield to my distinguished colleague from 
North Carolina.


               OPENING REMARKS OF SENATOR LAUCH FAIRCLOTH


    Senator  Faircloth. Thank you, Chairman Specter. Thank you 
for holding this hearing.
    As you know, we are gathered today to respond to the recent 
NIH decision to stop one of their research trials 14 months 
earlier than planned. This decision has resulted in both 
celebration and some confusion and concern.
    But this announcement offers hope for the first time to 
women of great risk of developing breast cancer, women who live 
with the knowledge that every woman in every generation in 
their family has developed the disease.
    For the first time, women will be able to take steps to 
protect themselves from developing breast cancer by taking a 
pill every day. This is certainly an exciting and remarkable 
step forward.
    I want to commend the NIH for stopping the trial once the 
results became known. You cannot argue with a 45-percent 
reduction in breast cancer.
    But I especially want to commend the women, the brave 
women, who were willing to enter this trial before these 
results were known. These women fought for this trial to be 
held and for their right to participate in it. They did so on 
behalf of their sisters, daughters, nieces, aunts, mothers, and 
grandmothers. They did it for women all over. We owe them a 
debt of thanks.
    We also owe them our promise that we will exercise 
responsibility in communicating this remarkable news as quickly 
and as widely as possible and address any questions about risks 
and side effects which demand attention.
    I thank you, Mr. Chairman, and I look forward to hearing 
the testimony.
    Senator Specter. Thank you very much, Senator Faircloth.
    We would like to proceed with our customary approach of 5 
minutes for opening statements. To the extent that the 
witnesses can conform to that, it would be appreciated. If you 
take some extra time, we understand that.
    All statements will be made a part of the record.


                 SUMMARY STATEMENT OF DR. HAROLD VARMUS


    We are going to lead off now with Dr. Harold Varmus, who 
has been Director of the National Institutes of Health since 
November 1993. While at the University of California at San 
Francisco, Dr. Varmus earned the Nobel Prize for his work on 
the causative link between certain genes and cancer. He is a 
graduate of Amherst College, Harvard University, and the 
Columbia Medical School.
    Again, Dr. Varmus, you are a frequent guest, visitor, 
lecturer, and witness here. You may proceed.
    Dr. Varmus. Thank you very much, Mr. Chairman. I want to 
congratulate you for holding this very timely hearing to 
discuss these extremely important issues.
    Senator Faircloth, thanks to you as well.
    Before other members of the panel talk about the topic that 
has brought us here today, namely the tamoxifen trial, I would 
like to provide a very brief perspective on prevention and the 
kind of research on which it is based.
    At the NIH, indeed medical research in general has a long 
and deep commitment to various strategies for preventing 
disease, strategies that block the initiation of disease 
processes, strategies that slow the appearance of 
manifestations of disease, and strategies that reduce the 
complications of disease.
    The techniques and methods that underlie these strategies 
include vaccines against infections. They include healthy 
behaviors--low fat diet, exercise, smoking cessation, and the 
avoidance of risks, such as accidents or sexually transmitted 
infections.
    Strategies to prevent disease include early diagnosis, like 
colonoscopy, blood pressure measurements, various x-ray 
techniques, including mammography, tests for prostate specific 
antigen and other indicators of early disease, screening for 
eye disease by examination.
    The last strategy includes the use of medications, the 
topic of today's discussion, which is used to control diabetes 
or hypertension, to reduce cholesterol levels or to interfere 
with transmission of HIV from mother to child. There are many 
such drug based prevention strategies.
    These strategies each incorporate a wide range of risks and 
benefits for every individual who undertakes them. Let me give 
you a couple of examples.
    Smoking cessation may be difficult for an individual to 
achieve, but it presents, by itself, no risk and offers major 
reductions in the incidents of certain common diseases.
    Exercise, another example, entails little risk but offers 
modest reduction in the incidence of some common diseases. 
Vaccines may be associated with a little more risk in some 
cases, but often protect nearly completely against diseases, 
some common and some uncommon diseases.
    The use of a variety of drugs to reduce cholesterol levels 
or to control blood pressure will protect some, but not all, 
against coronary artery disease or renal disease with small or 
uncertain long-term risks.
    There are many other examples, such as use of aspirin to 
try to reduce the incidence of coronary artery disease, again 
associated with a small degree of risk and some modest benefit.
    Now in most of these situations, we ask the patient and the 
patient's doctor to consider all of the available information 
and then to make an individual decision. This is also true of 
the situation that applies to the topic here today, the 
chemoprevention of cancer, as we will discuss in more detail.
    Now across this very broad range of prevention activities, 
we at the NIH are committed to obtaining through research that 
information that is necessary to make those decisions, and we 
are committed to transmitting the information that our research 
develops to the physicians and patients in a way that serves 
the patients' interests.
    Thanks very much.
    Senator Specter. Thank you very much, Dr. Varmus.


                SUMMARY STATEMENT OF DR. NORMAN WOLMARK


    Our next witness is the distinguished Dr. Norman Wolmark, 
president of the National Surgical Breast and Bowel Project, 
which oversees the National Breast Cancer Prevention Trial.
    He is a principal investigator of the study's operation 
center, located at the Allegheny Campus of the Allegheny 
University of Health Sciences, a graduate of McGill University 
Medical School, professor and chairman of the Allegheny 
University's Department of Human Oncology of the Health 
Sciences.
    Welcome, Dr. Wolmark. We look forward to your testimony. 
The floor is yours.
    Dr. Wolmark. Thank you, Senator Specter, Senator Faircloth. 
I am grateful for the opportunity to review the data from the 
breast cancer prevention trial which, after all, is the basis 
of this afternoon's discussion. I would briefly like to 
summarize the conduct of this study.
    Senator  Faircloth. Doctor, if you don't mind, would you 
pull the microphone up much closer, please.
    Dr. Wolmark. Much closer. Very well.
    How's that?
    Senator  Faircloth. That's fine. Thank you, and I'm sorry.
    Dr. Wolmark. Between June 1992 and September 1997, 13,388 
women 35 years of age or older who were at increased risk for 
the development of breast cancer were randomized to receive 
either a placebo or tamoxifen for a period of 5 years. Neither 
the participant nor her physician was aware of the allocated 
treatment.
    Women were eligible for this study if their breast cancer 
risk was at least as great as that of a 60-year-old woman.
    An independent data monitoring committee not affiliated 
with the NSABP was established to review the risks and benefits 
of treatment on an ongoing basis. Following a regularly 
scheduled meeting of this committee on Tuesday, March 24, 1998, 
it was concluded that the primary endpoint of the study had 
been met, namely, that there was a substantial reduction of the 
incidence of invasive cancer attributable to the use of 
tamoxifen and that the overall benefits of treatment outweighed 
the overall risks.
    It was only after this conclusion was reached that I or any 
other member of the NSABP operation center had an opportunity 
to review the results. The findings were then shared with Dr. 
Klausner, Director of the National Cancer Institute on 
Thursday, March 26, 1998, and we agreed to accept the 
recommendations of the data monitoring committee.
    It was concluded that any additional data that could be 
gained by continuing the study in its double blinded form did 
not justify withholding this information from the participants. 
The results were publicly disclosed during a press conference 
held on Monday, April 6, 1998.
    The reduction in the incidence of breast cancer as a result 
of tamoxifen treatment was highly significant. With a meantime 
on study of approximately 4 years, there was a 45-percent 
reduction in the number of invasive breast cancers and the data 
appear on the plotted graphs to your left, on the poster.
    There were 154 invasive breast cancers in the group 
assigned to the placebo, compared with 85 in women who had 
received tamoxifen. There was a concomitant reduction in the 
incidence of noninvasive breast cancer from 59 in the placebo 
group to 31 for women treated with tamoxifen. These differences 
were seen across all age groups.
    Tamoxifen also reduced the number of hip, wrist, and spine 
fractures from 71 in the placebo group to 47 in the treated 
participants.
    The use of tamoxifen was also associated with infrequent, 
but potentially life-threatening, adverse events. Although 
these adverse events were no greater than had been predicted 
prior to the initiation of the study, they must be given 
careful consideration in determining the propriety and utility 
of tamoxifen.
    The risks associated with tamoxifen appear on the bar graph 
to your right. The risk of tamoxifen associated adverse events 
was predominant in women older than 49 years of age. In this 
age group, there were 26 endometrial cancers in the tamoxifen 
treated group compared with 6 in the placebo group. There was 
also an excess of vascular events, or thromboembolic phenomena, 
stroke or transient ischemic attacks, 81 in the tamoxifen group 
versus 53 in the placebo group. The increased risk of vascular 
events was similar to that noted in postmenopausal women taking 
hormonal replacement therapy.
    There was no increased incidence of ischemic heart disease, 
including myocardial infarction.
    We can conclude that the benefits of tamoxifen are achieved 
at the price of an increased incidence of adverse events.
    There are, however, well defined patient categories in whom 
the benefits appear to outweigh the risks. These categories 
include: (1) Women who are under 50 years of age in whom, to 
date, there has been no excess of endometrial cancer or 
thromboembolic phenomena; (2) women older than 49 years of age 
who have had a hysterectomy. This is not a small group and it 
actually comprised 37 percent of all women entered into our 
study. Finally, and in all likelihood, the third group were 
women with a history of lobular carcinoma in situ or atypical 
hyperplasia.
    Senator Specter, in your introductory remarks you mentioned 
that another drug is on the horizon which seems to have 
equivalent efficacy to tamoxifen with perhaps fewer adverse 
effects. We believe that it is absolutely critical to determine 
what the true efficacy of raloxifene is compared to tamoxifen 
using the scientific method, namely that of a large, 
randomized, prospective clinical trial.
    We also view this trial, the breast cancer prevention 
trial, as only one step in a continuum that will undoubtedly 
lead to better agents with fewer adverse side effects. And in 
order to be able to accomplish this vital task, we will require 
the total support and commitment of you and the other members 
of this committee.

                           PREPARED STATEMENT

    In conclusion, I would like to echo the remarks made by 
Senator Faircloth, which is to acknowledge the courage, the 
conviction, the selflessness, the dedication of the 13,388 
women who participated in this trial. Clearly, this is their 
achievement and the recognition belongs to them.
    Thank you.
    [The statement follows:]


                Prepared Statement of Dr. Norman Wolmark

    Good afternoon, Senator Spector and members of the Subcommittee. I 
am Norman Wolmark, Chairman of the National Surgical Adjuvant Breast 
and Bowel Project (NSABP).
    In April of 1992, the NSABP, with funding from the National Cancer 
Institute, initiated the Breast Cancer Prevention Trial (BCPT) in order 
to determine whether the non-steroidal anti-estrogen, tamoxifen, could 
reduce the incidence of breast cancer in women who were at high risk 
for the development of the disease. Prior to initiation, the study was 
approved by an NCI appointed peer review committee, the Food and Drug 
Administration, the Office for Protection from Research Risks (OPRR) 
and the Institutional Review Boards of the more than 300 institutions 
who enrolled participants in the trial. In addition, an Endpoint 
Review, Safety Monitoring, and Advisory Committee (ERSMAC) was 
established and charged with the task of reviewing the toxicity of 
treatment and adverse side effects, as well as the effectiveness of 
tamoxifen. ERSMAC members were not affiliated with the NSABP. The data 
were not available to me or to any other member of the NSABP Operations 
Center until it had been determined by this committee that the primary 
endpoint of the trial had been met. ERSMAC functioned in an independent 
manner and the recommendation to disclose the data was made taking into 
account the benefits and risks of tamoxifen therapy.
    Between June of 1992 and September of 1997, 13,388 women 35 years 
of age or older who were at increased risk for the development of 
breast cancer were randomized to receive either a placebo or tamoxifen 
for a period of 5 years; neither the participant nor her physician was 
aware of the allocated treatment. Women were eligible for this study if 
their breast cancer risk was at least as great as that of a woman 60 
years of age.
    Following a regularly scheduled meeting on Tuesday, March 24, 1998, 
ERSMAC members concluded that the primary endpoint of the study had 
been met, namely, that there was a substantial reduction in the 
incidence of invasive breast cancer attributable to the use of 
tamoxifen and that the overall benefits of treatment outweighed the 
overall risks. It was only after this conclusion was reached that I or 
any other members of the NSABP Operations Center had an opportunity to 
review the results. The findings were then shared with Richard 
Klausner, M.D., Director of the National Cancer Institute and other 
representatives of the National Cancer Institute on Thursday, March 26, 
1998 and we agreed to accept the recommendations of ERSMAC. It was 
concluded that any additional information that could be gained by 
continuing the study in its double-blinded form did not justify 
withholding this information from the participants. The results were 
publicly disclosed during a press conference held on Monday, April 6, 
1998.
    The reduction in the incidence of breast cancer as a result of 
tamoxifen treatment was highly significant. With a mean-time on study 
of approximately 4 years, there was a 45-percent-reduction in the 
number of invasive breast cancers; there were 154 invasive breast 
cancers in the group assigned to placebo compared with 85 in women who 
had received tamoxifen. There was a concomitant reduction in the 
incidence of non-invasive breast cancer from 59 in the placebo group to 
31 for women treated with tamoxifen. The reduction in the incidence of 
breast cancer was seen across all age groups and the magnitude of this 
reduction persisted throughout the period of available follow-up. 
Tamoxifen also reduced the number of hip, wrist and spine fractures 
from 71 in the placebo group to 47 in treated participants.
    The use of tamoxifen was also associated with infrequent but 
potentially life-threatening adverse events. Although these adverse 
events were no greater than had been predicted prior to the initiation 
of the study, they must be given careful consideration in determining 
the propriety and utility of tamoxifen in reducing breast cancer risk. 
The risk of tamoxifen-associated adverse events was predominant in 
women older than 49 years of age. In this age group, there were 26 
endometrial cancers (cancer of the uterus) in the tamoxifen treated 
participants compared with 6 in the placebo group. There was also an 
excess of ``vascular events'' (thromboembolic phenomena, stroke and 
transient ischemic attacks), 81 in the tamoxifen group versus 53 in the 
placebo group. The increased risk of ``vascular events'' was similar to 
that noted in postmenopausal women taking hormonal replacement therapy. 
There was no increased incidence of ischemic heart disease including 
myocardial infarction.
    The results of this study are the first from a randomized 
prospective trial to show that tamoxifen can significantly reduce the 
incidence of breast cancer in women who are at high risk for the 
development of this disease. When considering the use of tamoxifen in 
order to decrease the incidence of breast cancer, one must weigh the 
benefits against the adverse effects. Having said this, there are well 
defined patient categories in whom the benefits appear to outweigh the 
risks. These categories include: (1) women who are under 50 years of 
age in whom, to date, there has been no excess of endometrial cancer 
and thromboembolic events; (2) women older than 49 years who have had 
hysterectomies (a group which represented 37 percent of all women 
entered into this study); and (3) women with a history of lobular 
carcinoma in situ or atypical hyperplasia.
    Efforts are currently underway to better define the risk benefit 
ratio associated with tamoxifen. This task must be carried out in a 
careful, methodic and step-wise manner. The model that was used to 
predict the risk of breast cancer prior to the initiation of the study 
must now be refined in light of the actual breast cancer incidence 
observed. This may enable the revised model to more accurately define 
the risk benefit ratio of tamoxifen treatment in specific populations. 
These efforts have been initiated by the NCI and members of the NSABP 
Biostatistical Center.
    It must be emphasized that the results from this study apply only 
to women who are at increased risk for the development of breast cancer 
and have characteristics that would have made them eligible for this 
study. Examples of these high risk characteristics appear in Attachment 
A. Results of this trial as well as the characteristics that defined 
high risk, have been disseminated through the April 6, 1998 joint NCI/
NSABP press release and related documents including commonly asked 
questions with answers and copies of tables of the data presented at 
the press conference of April 6, 1998. This information has been placed 
on two internet web pages: the NCI Clinical Trials page (>http://cancer 
trials.nci.nih.gov<) and the NSABP web page (>http://
www.nsabp.pitt.edu<). In addition to the broadcast of the press 
conference on national television, the results of the trial have been 
publicized in the press. Responses to a recent survey distributed by 
the NSABP to individuals at BCPT participating sites and feed-back from 
our Participant Advisory Board indicate that, on the whole, women have 
responded in a measured and thoughtful manner to the information.
    From a global perspective, it is important not to regard this 
chemoprevention trial as an isolated study, but rather as part of a 
continuum of studies that will enhance our understanding of breast 
cancer. This study is a clear demonstration of proof of principle that 
the evolution of this disease can be altered. It is our hope that the 
results from the present study will lead to the rapid implementation of 
the next chemoprevention trial in which it is anticipated that 
effective agents with fewer side-effects can be identified. If this 
effort is to succeed, we will require the continued help and support of 
this Subcommittee.
    Finally, I would like to acknowledge the courage, dedication and 
perseverance of the 13,388 women who participated in this study. This 
is their trial and the credit for the findings belongs to them.

                        TAMOXIFEN AND RALOXIFENE

    Senator Specter. Dr. Wolmark, before proceeding to Dr. 
Klausner, let me assure you that you have my support and I am 
confident the support of the entire subcommittee, full 
Appropriations Committee and the Congress. We want to be as 
helpful as we can. With the public news in the last couple of 
weeks about tamoxifen and the news yesterday about raloxifene, 
we want to know what we can do further to help.
    Dr. Klausner has made the comment publicly and we will hear 
from him in a moment or two about the fact that there is no 
easy message to send home at this particular point given the 
side effects.
    What we want to do is to find out what the timeline is. 
When do you expect to be able to answer some of the questions 
about tamoxifen, as to the collateral problems which have 
appeared in the news media. What are the relative benefits of 
raloxifene? It has less on some forms of cancer, such as 
cervical cancer, as I read in the media, and when results can 
be expected and whether additional funding at this time would 
expedite the processes which you are under.
    So those are the issues which we look at here today. We 
want your guidance as to how we can be helpful to you. This is 
the place to come, the appropriations subcommittee.
    Dr. Klausner, welcome again to the subcommittee. Dr. 
Richard Klausner is the 11th Director of the National Cancer 
Institute with a research specialty in the regulation of 
genetic networks in human cells. He is a graduate of Yale 
University and Duke Medical School. He has served in a variety 
of leadership posts in the medical research community at NIH 
and has published extensively in the scientific literature.
    Thank you for joining us, Dr. Klausner. The floor is yours.

              SUMMARY STATEMENT OF DR. RICHARD D. KLAUSNER

    Dr. Klausner. Thank you, Mr. Chairman and Senator 
Faircloth.
    Let me make a few points about this study. First, it is a 
step forward and, to answer your query, it would not have 
happened without the support of the NIH. It takes us across a 
threshold into a new area of cancer research and, ultimately, 
of cancer practice but with new questions and new conundrums. 
It is the offspring of much previous work and it must be 
followed by a good deal more for many questions remain.
    As Dr. Wolmark said, with this study women at high risk of 
breast cancer now have, for the first time, a demonstrated 
option to consider in order to lower their risk. While this 
study did demonstrate an overall 45 percent risk reduction, we 
would like to know many things: whether tamoxifen delays the 
discovery of breast cancer or truly prevents it, perhaps by 
destroying very early cancers or precancerous lesions. We do 
not yet know for how long tamoxifen can or should be given. We 
do not know if it would be possible to predict whether certain 
women at high risk for breast cancer would benefit more or less 
than others from tamoxifen.
    If chemoprevention of cancer is to work, which I believe it 
will and which this study demonstrates in principle, we will 
need even more effective agents and agents with fewer side 
effects.
    We are confident that newer, selective estrogen response 
modifiers, this whole class of chemicals called SERM's, will be 
available at least for testing for future clinical trials, for 
they are the only way in which we will determine whether, 
indeed, new agents have those desired characteristics.
    As we have all emphasized, the decision to consider 
tamoxifen for preventing breast cancer is a very complex one 
and one that must be made between a woman and her physician.
    It will depend first upon a best attempt to assess the risk 
that any particular woman has of getting breast cancer. The 
expected reduction of that risk that this study gives and the 
clear risks of side effects also demonstrate it.
    Weighing the benefit of a reduced risk of one disease as 
opposed to an increased risk of other problems can in part be 
calculated but, in the end, will depend very much on how all of 
these risks are perceived by each woman.
    There will be no cut and dry formula for this. What is 
necessary is the delivery of clear and useful information which 
the NCI and the NSABP has, we believe, been trying to do. In 
fact, we are particularly concerned as to how the information 
that has been released over the last several weeks has served, 
or whether it has served, the needs of women and their 
physicians.
    Soon after the release of the study, the NCI began 
monitoring over 300 NSABP sites, all 57 NCI cancer centers, the 
19 regional centers of the Cancer Information Service, and 
directors of 10 advocacy organizations to determine whether 
physicians and women felt they had adequate information to 
respond to inquiries and their concerns.
    About 3,500 inquiries to date have been analyzed and the 
majority have felt that the information available was adequate. 
And we are also using the many questions that we received in 
this input to update and improve constantly the resources 
available to people.
    The message that we should not rush to judgment, that we 
cannot oversimplify this message, was clear from all.
    In my discussions with physicians and with advocacy groups 
at multiple recent town meetings that I have had around the 
country, with our cancer centers, with directors of the 
American Society of Clinical Oncology and many others, we all 
agree that the deliberate process of digesting new information, 
of discussion, and the dissemination of information is how we 
will all proceed.
    I would like to commend the media for what I think has 
really been a superb job at reporting the excitement, the 
limitations, the complexity and the caution that attends this 
study and for communicating well the personal decisionmaking 
that the emerging availability of preventive interventions for 
cancer will demand. If there is any one take-home message, it 
is one of individual risk.
    In moving forward, the NCI will work to help communicate 
tools to physicians to calculate a woman's risk of breast 
cancer along with her. We are now making available breast 
cancer risk determination materials to health care providers. 
They can be obtained through our website, through the Internet, 
by e-mail, or through the telephone based Cancer Information 
Service to enable physicians to utilize the risk models that we 
used in this study.
    Importantly, we will soon convene and support the much 
needed research to continue to improve and refine risk 
assessment. We will, as I said, support the critical research 
we need to answer questions about whether other agents are more 
effective and with less side effects and work to help try to 
define those for whom taking these drugs poses a risk.

                           PREPARED STATEMENT

    Our colleagues at Pittsburgh and elsewhere, and especially 
all the women who participated in this trial, are to be 
congratulated. That we move forward from this point with 
deliberative wisdom of the community is the prudent, indeed the 
only, way to best serve women at risk for breast cancer.
    We all thank you and the committee for your support of the 
NIH, support that enables us to conduct important studies, such 
as these.
    Senator Specter. Thank you, Dr. Klausner.
    [The statement follows:]


             Prepared Statement of Dr. Richard D. Klausner

    Good afternoon, Senator Specter and members of the subcommittee. I 
am Richard Klausner, Director of the National Cancer Institute (NCI). I 
am pleased to testify before you today on a remarkable advance in 
cancer prevention.
    The goal of preventing cancer has long been a hope and a central 
focus of the National Cancer Program. Prevention can take many forms, 
from smoking cessation and other behavioral changes to vaccines or 
antimicrobial agents against cancer-causing infections to a new field 
in which medicines specifically interfere with the biologic processes 
of cancer development. For the past several years, the National 
Surgical Adjuvant Breast and Bowel Project (NSABP), an NCI-funded 
national clinical trials organization, has been carrying out a historic 
trial--called the Breast Cancer Prevention Trial, or BCPT--to determine 
whether women at increased risk of developing breast cancer can prevent 
the development of that cancer by taking a well-known medicine, 
tamoxifen. More than 13,000 women who participated in this study have 
been our partners in this work.
    As with all of our clinical trials, an independent Endpoint Review, 
Safety Monitoring, and Advisory Committee regularly examines the data 
generated by the study to monitor whether either unacceptable or 
unexpected toxicities have arisen or whether the trial has succeeded in 
answering the questions it has been designed to answer. This committee 
met most recently on March 24. The committee concluded that the 
question of whether tamoxifen can significantly reduce the incidence of 
breast cancer in women at increased risk had been answered; and the 
answer is an unequivocal yes. Nevertheless, there were, as you have 
heard, adverse effects of tamoxifen which may make the very personal 
decision about taking tamoxifen complex. For all of these reasons, the 
committee recommended that the participants of the study be notified of 
these important results. It has been our commitment to the participants 
from the very start to notify them as soon as clear results had been 
achieved.
    On March 26, the NSABP leadership presented these recommendations 
and the data behind them to the NCI and we--NCI and NSABP--agreed to 
accept the recommendations of the independent advisory committee. This 
afternoon, NCI and NSABP will share this information with you, 
describing the study, its results, and its implications, and very 
importantly, place this study in the context of the larger march of 
science and research towards the control of this dread disease.
    The results are remarkable. They tell us that breast cancer can be 
prevented. A forty-five percent decrease in the incidence of this 
disease represents one of the more dramatic findings we have seen. They 
represent the power of the Nation's investment in research and the 
value of carefully conducted clinical trials. The insight that 
tamoxifen might prevent breast cancer came from another NSABP clinical 
trial for the treatment of breast cancer. That this drug does prevent 
breast cancer fits with our deep understanding of the role of estrogen 
and estrogen receptors in breast cancer and an enormous amount of 
science about this drug, which has been under study for over 25 years.
    While it is tempting to generalize, our conclusions must adhere to 
the data available. For women whose predicted risks of breast cancer 
match those of the participants of this study, they have the option to 
take tamoxifen with confidence that it can lower the risk of developing 
breast cancer. This study provides the evidence for the magnitude of 
this reduction, as well as the extent of a variety of risks that women 
who take this drug could face. Women need to discuss with their 
physicians their own risks for breast cancer and the benefits and risks 
of taking tamoxifen. The NCI will provide information about this study 
to the public and health care providers through the Cancer Information 
Service (CIS) and through PDQ and the new NCI clinical trials web site. 
The data from this study will continue to be analyzed and the 
information will be made available through peer reviewed publications 
and via the different communication outlets of the NCI.
    The NCI is committed to communicating the importance of research 
findings to women and their physicians in a clear and understandable 
manner. NCI has solicited feedback about the impact the Breast Cancer 
Prevention Trial announcement has had on those who counsel women 
regarding their decision to take tamoxifen for the prevention of breast 
cancer. The feedback concerning the handling of the announcement and 
the materials provided to date has been very positive. This feedback is 
being used to assist NCI and the NSABP to develop tools to help each 
woman, and her health care provider, when making a decision about 
whether use of tamoxifen is appropriate for her.
    The preliminary findings from a survey of Cancer Center Directors, 
NCI's Cancer Information Service, Principal Investigators of the NSABP, 
and the advocacy community indicate that it has been possible for them 
to respond to most inquiries and counseling requests using information 
already provided by NCI and NSABP. This information was disseminated 
through existing NCI and NSABP communication mechanisms before or at 
the time of the public announcement of the trial's early results. A new 
mechanism was also used. NCI launched on the day of the announcement a 
new clinical trials web site, which included information about the 
benefits and risks of tamoxifen.
    For women whose risks of developing breast cancer fall within the 
range of this study, tamoxifen can provide, for the first time, an 
option to reduce that risk, much as new cholesterol-lowering medication 
can reduce the risk of heart attacks. But that option must be weighed 
carefully and on an individual basis.
    This emphasis on individual risk is important. Our ability to 
identify individuals at risk for disease and to begin to rationally 
intervene, based upon our knowledge of the disease process, is what 
medicine will become.
    Great interest has been generated about genetic predisposition to 
breast cancer, and we know that some breast cancer is linked to certain 
mutations. It is likely that some of the women in this study, 
especially those with very strong family histories of breast cancer, 
carry such a genetic predisposition. While it is reasonable that such 
women would also experience a decreased risk of breast cancer with 
tamoxifen, no specific gene testing has been done. As further analyses 
of the data from this clinical trial are done, we hope to be able to 
provide more information over the next 6-12 months as to whether women 
with alterations in BRCA 1 and 2, the two known genes whose alterations 
predispose to breast cancer, were protected from cancer in this trial. 
I would like to emphasize, however, that there are many important 
considerations as to how new knowledge about genetics can and should be 
made a part of medical decision-making that further complicate this 
process.
    This study is not an end. It is rather a very propitious beginning. 
But it tells us that it is possible to prevent breast cancer. Tamoxifen 
is far from ideal. Its efficacy is only partial and it has significant 
risks. To move forward will require new agents and new clinical trials. 
Newer selective estrogen receptor modifiers are being developed and 
will be tested. The NCI hopes to be able to follow this study soon with 
additional clinical trials to find answers to the many questions that 
remain.
    Thank you, Mr. Chairman, for your continued support for cancer 
research. I would be pleased to answer any questions the Subcommittee 
may have.

                           HIGH RISK CATEGORY

    Senator Specter. Before moving to Ms. Wilson, let me ask 
you a question which is on the minds of people who have heard 
you generally and certainly people who have heard you today. A 
woman knows she is in the high risk category for breast cancer. 
She has seen the preliminary studies. She knows that there are 
possible, adverse side effects. She wants to take tamoxifen. Is 
it available for her today if her individual doctor prescribes 
it?
    Dr. Klausner. Of course, tamoxifen is an approved drug and 
so a physician certainly could prescribe it. We want to 
emphasize that for those women, it is important to sit down 
with their physician to make sure that perceived risk of breast 
cancer is accurate and to understand what possible side effects 
she might experience, how to look for them. And, as Dr. Wolmark 
said, even with that, one size does not fit all. Women below 50 
seem to experience, so far in these 4 years of this study, no 
significant increased risk associated with tamoxifen. But we 
need to see how that goes. Women above 50 had significant 
risks.
    We are concerned about the underlying risk factors of women 
which they might have for clotting events and whether or not a 
woman has a uterus. It is uterine cancer that was the cancer 
that is increased from taking tamoxifen.
    So the message very much is each woman is different. The 
message of hope, I think as you will hear from Ms. Wilson, is 
that there are many women who are at very high risk of breast 
cancer and this does provide an option.
    Senator Specter. So the option of tamoxifen is available 
today with the categories and risks outlined. The specifics 
ought to be reviewed by her own physician, but help is 
presently available with tamoxifen.
    Dr. Klausner. Of course, this drug is not approved by the 
FDA for this use. Immediately upon receiving this information, 
the data from NSABP, from the study, was forwarded to the FDA, 
as well as to the company that provided the tamoxifen, Zeneca, 
and a process will begin, has begun, in an expedited way, to 
review all of this data by the FDA in order to evaluate it for 
this indication.
    Senator Specter. Dr. Klausner, as you say, tamoxifen has 
been approved by the FDA but it has not been approved for this 
specific purpose.
    Dr. Klausner. That's right.
    Senator Specter. A physician may prescribe an approved drug 
for another purpose if the physician feels that it meets the 
needs and is a remedy for that other purpose.
    Dr. Klausner. That's right, sir.
    Senator Specter. So even though it is not approved for 
breast cancer, a doctor may prescribe tamoxifen for breast 
cancer.
    Dr. Klausner. It is approved actually for breast cancer in 
the treatment setting. We are talking about being approved not 
for breast cancer but for use in healthy women to reduce the 
risk of breast cancer that the FDA will be looking at.
    Dr. Varmus. I might add, Senator Specter, that Michael 
Friedman, who is the lead deputy of the FDA, has promised that 
he will complete the FDA review of this particular use within 6 
months.

                   SUMMARY STATEMENT OF HELENE WILSON

    Senator Specter. Well, we want to explore why 6 months. We 
will do that after we hear from Ms. Wilson.
    Ms. Wilson, welcome.
    Ms. Wilson is a resident of North Wales, PA, a patient in 
the tamoxifen clinical trial. She is a registered nurse who 
manages clinical trials for a major pharmaceutical company and 
also serves as a member of the study's participant advisory 
board.
    She is a nursing graduate of Mercy College.
    We welcome you here today, Ms. Wilson, and look forward to 
your testimony.
    Ms. Wilson. Good afternoon and thank you very much for 
inviting me this afternoon to testify about my experience as a 
participant in the NSABP breast cancer prevention trial.
    As you just mentioned, I am a resident of North Wales, PA, 
a registered nurse and a divorced mother of two children. I 
have a daughter, age 30, a son, age 26, and I have a 
granddaughter, age 1.
    I am currently employed by Merck & Co., where I am a senior 
manager in clinical research and manage clinical trials using 
our Merck products.
    This career has provided me with experience and an 
understanding of the conduct and efficacy issues surrounding 
clinical trials.
    I became a participant in the breast cancer prevention 
trial, the BCPT, in October 1992, and finished taking my 5 
years of study drug therapy which actually turned out to be 
tamoxifen therapy in October 1997.
    When I discovered that I was eligible to participate in the 
BCPT, I felt as though I had won the lottery. I was elated at 
being offered a chance to take a proactive step toward 
preventing breast cancer.
    My maternal grandmother, my mother, my mother's sister, and 
my father's sister all died of breast cancer. And as if this 
were not enough devastation for one family to endure, early 
signs of this dreadful disease began affecting me. I have had 
approximately seven biopsies, most of which turned out to be 
benign.
    However, the last few biopsies showed signs of atypical 
hyperplasia and microcalcifications, both thought to be strong 
indications of impending breast cancer. In my doctor's words, I 
was a ``walking time bomb.''
    People have asked why I joined the trial. Because of my 
strong family history and what was beginning to be a personal 
history, I felt that enough is enough. I needed to do something 
other than just wait for the cancer to occur. Before hearing 
about the BCPT, I was seriously considering undergoing a 
procedure called prophylactic mastectomy. That is a procedure 
where both breasts and the surrounding tissue are removed. This 
would have been an attempt to escape the onset of breast 
cancer.
    Since even this drastic step did not offer complete 
confidence that I would not develop breast cancer, I decided to 
forego the mastectomies until I heard more about the BCPT.
    I met with individuals at our local hospital, the 
Montgomery Cancer Center, who extensively explained the study, 
the consent form, and the risks and benefits of tamoxifen and 
participating in a clinical trial. I completed a risk 
assessment form used to evaluate my relative risk for 
developing breast cancer, underwent blood tests, a physical, a 
gynecologic exam, a mammogram, and was finally accepted into 
the trial as a participant.
    Being a participant in the BCPT has been a very positive 
experience. I feel that I am doing something proactive in my 
own care, which is very important to me. I do not want to sit 
back and just wait for breast cancer to strike. Participating 
in this clinical trial has allowed me to become more aware of 
my own health and at the same time I am taking a step forward 
for future generations.
    I was informed throughout the trial of all information. 
Shortly after the trial started, the NSABP committed to 
informing participants of any new information before the media 
and before the general public. The NSABP appointed a 
participant advisory board, the PAB, of which I am a member. 
This board consists of a group of 16 participants, whose 
purpose is to offer a voice for all participants and to assist 
in communicating the concerns and thoughts of the women in the 
trial.
    The NSABP also implemented other tactics to strengthen the 
commitment they had promised to the participants of the trial. 
They developed a newsletter to update participants between 
office visits and there was always a phone number available 
where questions could be answered or concerns addressed.
    Additionally, women in the trial were reconsented when any 
new information about tamoxifen emerged. During my reconsenting 
process, additional risks were identified and explained to me 
and I was given the option to withdraw my consent or to 
continue to participate in the trial.
    The NSABP has truly kept its promise and it made a great 
effort to keep participants informed every step of the way in 
this trial.
    Throughout the conduct of the trial, I felt that I was 
given all new information with full explanations and in a 
timely manner.
    As a participant advisory board member, I was told of the 
initial results during a conference call with all PAB members. 
It is my understanding that other participants received a call 
from their study coordinator or they received a letter that 
explained that the initial results of the BCPT were available. 
The letter that came to me as a participant in the trial 
contained instructions for me to contact my study doctor to 
learn which arm of therapy I had been assigned. The letter also 
explained that these results were initial and that more 
information would be forthcoming at a later date once the data 
was more fully analyzed.
    Although there are no concrete prevention guidelines, I 
feel that this information adequately explained the initial 
findings of the BCPT to the participants who actually made the 
study possible. As a participant, the type of data that I was 
most interested in is the decreased rate of breast cancer. It 
lets us know that there is hope.
    Personally, as a participant, I was very happy to hear the 
results first. I know that if the information were not 
statistically significant, the NSABP would not have released 
the information. Additionally, I strongly believe that the 
participants needed to know. It would be unethical to keep a 
participant on placebo, an inactive agent, for up to 5 years 
when the comparative arm, tamoxifen therapy, did show a 
benefit.
    Also, the process for obtaining an indication from the FDA 
for tamoxifen for the prevention of breast cancer could not 
start until the trial was completed and the data fully 
analyzed.
    Although the manner used to release this information was 
unorthodox, I believe it was handled in an appropriate way. By 
that I mean in other clinical trials the results are presented 
at a scientific meeting or published in a peer review journal 
first, a process that has not been followed for this trial. But 
in a sense the entire trial has been unorthodox because it is 
evaluating a prevention for rather than a treatment of breast 
cancer.
    The use of a participant advisory board is also new and 
unconventional in clinical trials. All of these elements are 
different from the norm, but they work. It demonstrates that 
different does not always have to be wrong.
    I am an African-American and I have been asked on a number 
of occasions about the concern that the results may not apply 
to African-Americans because of the low minority representation 
in the BCPT. I am not concerned that we may not know if the 
results will apply to women of color. We do have a small 
minority representation in the BCPT and I am sure that, as the 
analysis of the data continues, researchers will look at the 
data from the women of color to see if there was any difference 
in this subgroup.
    The thing that does concern me was how difficult it was to 
recruit women of color to a clinical trial. I believe that 
there are cultural reasons why people of color do not 
participate in clinical trials. But I am concerned more that 
women of color do not get exposed to medical care at the level 
that most of the general population does nor do they have the 
same opportunities to participate in clinical trials.
    The NSABP attempted to change this by developing programs 
specifically intended for increasing minority representation in 
the BCPT. Nancy Wilson became a national spokesperson and 
similar efforts were attempted at the local level.
    I personally spoke at several African-American churches in 
an attempt to get women involved. Unfortunately, low minority 
representation is a phenomenon that is seen in all clinical 
trials.
    My interest in breast cancer prevention preceded my joining 
the trial. Having lived through seeing my mother and aunt dying 
of breast cancer, I saw how devastating this disease is to a 
woman and how it affects her whole family.
    My goddaughters, at the ages of 4 and 8, lost their mother 
to breast cancer. If we can do anything to prevent this breast 
cancer, we must.
    This is why this study is so important. The BCPT was the 
first step, which will lead to a next step, and a next step in 
successfully preventing breast cancer. I feel that my 
experience is not that different than my colleagues' on the 
participant advisory board and in the study as a whole and hope 
that I have been able to reflect their point of view as well as 
my own in this testimony.
    If I had the opportunity to say anything to women 
considering participating in a clinical trial, it would be 
this: It is important to evaluate where you are. Take a stand 
and make an effort to improve your health and the outlook for 
future generations. When you participate in a clinical trial, 
you receive excellent medical care. You are working toward 
making a difference.
    Women need to stand up and be counted, and it is important 
to do something proactive to improve women's health.
    If you participate, do so in a rational fashion. Know the 
risks, know the benefits, and become involved.

                           PREPARED STATEMENT

    Again, I wish to thank you, Mr. Chairman, for the 
opportunity to discuss this important issue and I would be 
pleased to answer any questions that you may have about my 
participation.
    Senator Specter. Thank you very much, Ms. Wilson.
    [The statement follows:]


                  Prepared Statement of Helene Wilson

    Good morning Mr. Chairman and members of the Subcommittee. My name 
is Helene Wilson. Thank you for inviting me to testify here today about 
my experience as a participant in the NSABP Breast Cancer Prevention 
Trial.
    I am 48 years old and reside in North Wales, Pennsylvania. I am a 
mother of two children (a daughter age 30 and a son age 26). I am 
currently employed by Merck and Company where I am a senior manager in 
clinical research, specializing in clinical trials using Merck agents. 
This career has provided me with experience and an understanding of the 
conduct and efficacy issues surrounding clinical trials. I became a 
participant of the Breast Cancer Prevention Trial (BCPT) in October 
1992, and finished my 5 years of tamoxifen therapy in October 1997.
    When I discovered that I was eligible to participate in the BCPT, I 
felt as though I had won the lottery. I was elated that I was being 
offered a chance to take a proactive step toward preventing breast 
cancer. My maternal grandmother, my mother, my mother's sister, and my 
father's sister had all died of breast cancer; and as if this were not 
enough devastation for one family to endure, early signs of this 
dreadful disease began afflicting me. I had approximately seven 
biopsies, most of which were benign; however, the last few biopsies 
showed signs of atypical hyperplasia and microcalcifications, both 
thought to be strong indications of impending breast cancer. In my 
doctor's words, I was a ``walking time bomb.''

                         WHY I JOINED THE TRIAL

    Before hearing about the BCPT, I was seriously considering 
undergoing a procedure called prophylactic mastectomy, where both 
breasts and the surrounding tissue would be removed, in an attempt to 
escape from this fear of breast cancer. Since even this drastic step 
did not offer complete confidence that I would not develop breast 
cancer, I decided to forego the prophylactic mastectomy until I heard 
more about the BCPT. Because of my strong family history, and what was 
beginning to be a personal history, I felt that enough is enough! I met 
with individuals at the Montgomery Cancer Center who extensively 
explained the study, the consent form, and the risks and benefits of 
tamoxifen and participating in a clinical trial. I completed a risk 
assessment form used to evaluate my relative risk for developing breast 
cancer, underwent blood tests, a physical, a gynecologic exam, a 
mammogram, and finally, was accepted into the trial as a participant.
    Being a participant in the BCPT has been a very positive experience 
for me. I feel that I am doing something proactive in my own care, 
which is important to me. I did not want to sit back and just wait for 
breast cancer to strike. Participating in this clinical trial has 
allowed me to become more aware of my own health--and at the same time, 
I am taking a step forward for future generations.

               HOW I WAS INFORMED AS THE TRIAL PROGRESSED

    Shortly after the trial started, the NSABP committed to informing 
participants of any new information before the media and before the 
general public. The NSABP also appointed a Participant Advisory Board 
(PAB), of which I am a member. This Board consists of a group of 16 
participants whose purpose is to offer a voice for all participants, 
and to assist in communicating the concerns and thoughts of the women 
in the trial. The NSABP also implemented other tactics to strengthen 
the commitment they had promised to the participants of this trial. 
They developed a newsletter which is used to update participants 
between office visits, and there was always a phone number available 
where questions could be answered or concerns could be addressed. 
Additionally, women in the trial were reconsented when any new 
information about tamoxifen emerged. During my reconsenting process, 
additional risks were identified and explained to me, and I was given 
the option to withdraw my consent or to continue my participation in 
the trial.
    The NSABP has truly kept its promise, and made a great effort to 
kept participants informed every step of the way in this trial. 
Throughout the conduct of the trial, I feel that I was given all new 
information with full explanations and in a timely manner.

                     MY JOY AT LEARNING THE RESULTS

    As a Participant Advisory Board member, I was told of the initial 
results during a conference call with all PAB members. It is my 
understanding that other participants received a call from their study 
coordinator, or they received a letter which explained that initial 
results of the BCPT were available. The letter that came to me as a 
participant in the trial contained instructions for me to contact my 
study doctor to learn which arm of therapy had been assigned to me. The 
letter also explained that the results were initial and that more 
information would be forthcoming at a later date once the data was more 
fully analyzed. Although there are no concrete prevention guidelines, I 
feel that this information adequately explained the initial findings of 
the BCPT to the participants who made it possible. As a participant, 
the type of data that I am most interested in is the decreased rate of 
breast cancer. There is hope.

                  TIMING OF THE RELEASE OF INFORMATION

    Personally, as a participant I was very happy to hear the results 
first. I know that if the information were not statistically 
significant, the NSABP would not have released the information. 
Additionally, participants needed to know. It would be unethical to 
keep a participant on placebo, an inactive agent, when the comparative 
arm, tamoxifen therapy, does show a benefit. Also, the process for 
obtaining an indication from the FDA for tamoxifen and the prevention 
of breast cancer could not start until the trial information was 
complete.
    Although the manner used to release this information was 
unorthodox, I truly believe it was handled in an appropriate way. By 
that I mean, in other clinical trials the results were published in a 
peer reviewed journal first, a process that has not been followed for 
this trial. In a sense, the entire trial is unorthodox because it is 
evaluating a prevention rather than a treatment. The use of a 
Participant Advisory Board was also new and unconventional in clinical 
trials. All of these elements are different from the norm but they 
worked. Different does not always have to be wrong.

                MINORITY RECRUITMENT TO CLINICAL TRIALS

    I am an African-American. I have been asked on a number of 
occasions about the concern that the results may not apply to African-
Americans because of the low minority representation in the BCPT. I am 
not concerned that the results may not apply to women of color. We did 
have a small representation percentage in the BCPT, but I am sure that 
as the analyses of the data continues, researchers will look at the 
women of color to see if there was any difference in this subgroup. The 
thing that concerned me most was how difficult it was to recruit women 
of color to a clinical trial. I think there are cultural reasons why 
people of color do not participate in clinical trials. I also believe 
that women of color do not get exposed to medical care at the level 
that most of the general population does nor do they have the same 
opportunities to participate in trials. The NSABP attempted to change 
this by developing programs specifically intended for increasing 
minority representation on the BCPT. Nancy Wilson became a national 
spokesperson, and similar efforts were attempted at each local level. I 
personally talked at several black churches to try to get women 
involved. Unfortunately, low minority representation is a phenomena 
that is seen in all clinical trials.
   advice to other women considering participation in clinical trials
    My interest in breast cancer prevention preceded my joining the 
trial. Having lived through seeing my mother and aunt dying of breast 
cancer, I saw how devastating this disease is to a woman and how it 
affects her whole family. My goddaughters (ages 6 and 8) recently lost 
their mother to breast cancer, and if we can do anything to prevent 
breast cancer--we must. This is why this study is so important. The 
BCPT was the first step which will lead to a next step in successfully 
preventing breast cancer. I feel that my experience is not that 
different from my colleagues on the Participant Advisory Board and hope 
that I have been able to reflect their point of view as well as my own 
in this testimony.
    It is important to evaluate where you are. Take a stand, and make 
an effort to improve your health and the outlook for future 
generations. When you participate in a clinical trial, you receive 
excellent medical care. You are working toward making a difference. 
Women need to stand up and be counted, and it is important to do 
something proactive to improve women's health. If you participate, do 
so in a rational fashion. Know the risks, the benefits, and become 
involved.
    Again, I wish to thank you, Mr. Chairman, for the opportunity to 
discuss this important issue. I would be pleased to answer any 
questions the subcommittee may have.
                                 ______
                                 


                              Attachment A

      National Surgical Adjuvant Breast and Bowel Project [NSABP]
     breast cancer prevention trial shows major benefit, some risk
    Six years after its inception, the Breast Cancer Prevention Trial 
(BCPT) shows a 45 percent reduction in breast cancer incidence among 
the high-risk participants who took tamoxifen (Nolvadex), a 
drug used for the past two decades to treat breast cancer.
    As a result, investigators released the initial study results about 
14 months earlier than expected and notified the 13,388 women 
participants of the findings so those women who had been taking a 
placebo could consider starting tamoxifen therapy after consulting with 
their personal physicians. Participants will continue to be followed by 
the National Surgical Adjuvant Breast and Bowel Project (NSABP), the 
Pittsburgh-based research network that conducted the trial with support 
from the National Cancer Institute (NCI).
    In this trial, healthy women assigned to take tamoxifen developed 
85 cases of invasive breast cancer compared to 154 cases in the women 
assigned to the placebo.
    Tamoxifen did increase the women's chances of three rare but life-
threatening health problems: there were 33 cases of endometrial cancer 
(cancer of the lining of the uterus) in the tamoxifen group versus 14 
cases in the placebo group; there were 17 cases of pulmonary embolism 
(blood clot in the lung) in the tamoxifen group versus six cases in the 
placebo group; and there were 30 cases of deep vein thrombosis (blood 
clots in major veins) in the tamoxifen group versus 19 cases in the 
placebo group.
    Among these women at increased risk for breast cancer, women under 
age 50 appeared to suffer no excess risk of adverse effects from use of 
tamoxifen.
    ``Women who are at an increased risk of breast cancer now have the 
option to consider taking tamoxifen to reduce their chances of 
developing breast cancer. As with any medical procedure or 
intervention, the decision to take tamoxifen is an individual one in 
which the benefits and risks must be considered,'' said Leslie Ford, 
M.D., associate director for early detection and community oncology in 
NCI's Division of Cancer Prevention. The choice will vary depending on 
a woman's age, personal history, family history, and how she weighs the 
benefits and risks.
    ``Even if a woman is at increased risk of breast cancer, tamoxifen 
therapy may not be appropriate for her,'' continued Ford. ``NSABP and 
NCI are developing information for individual decisionmaking that will 
help women at increased risk of breast cancer consult with their health 
care providers to answer the question, `Is tamoxifen the right choice 
for me?' ''
    The BCPT is a clinical trial designed to see whether the drug 
tamoxifen prevents breast cancer in women who are at an increased risk 
of developing the disease. Women in the study were randomly assigned to 
receive tamoxifen or a placebo pill and neither participants nor their 
physicians were aware of the treatment assignment, a process called 
``double-blinding.''
    Launched in April 1992, the BCPI also looked at whether taking 
tamoxifen decreases the number of heart attacks and reduces the number 
of bone fractures in these women There was no difference in the number 
of heart attacks between the tamoxifen and placebo group, but women in 
the tamoxifen group had fewer bone fractures of the hip, wrist, and 
spine (47 cases in the tamoxifen group versus 71 cases in the placebo 
group).
    As part of the study design, the BCPT data were regularly reviewed 
by an independent Endpoint Review, Safety Monitoring, and Advisory 
Committee (ERSMAC). At its regularly scheduled meeting on March 24, 
1998, the committee recommended that the participants and their 
physicians be told what pills each participant had been taking because 
of the clear evidence that tamoxifen reduced breast cancer risk.
    NSABP presented the data to NCI on March 26 and, together both 
NSABP and NCI researchers concurred with the committee's 
recommendation. This decision was based upon their joint assessment 
that a reduction of breast cancer had been demonstrated. It was agreed 
that any additional information that might be gained from continuing 
the study did not outweigh the benefits of making the treatment 
available to the participants in the placebo group and other women at 
increased risk of breast cancer.
    The women in the trial have taken tamoxifen or placebo daily for 
about four years. In spite of extensive efforts to enroll minorities in 
the BCPT, African American, Asian American, Hispanic, and other groups 
together made up only about three percent of the participants.
    About 40 percent of the participants were ages 35 to 49, 30 percent 
were ages 50 to 59, and 30 percent were age 60 or older. All age groups 
showed similar reductions in breast cancer incidence from tamoxifen. 
There was a suggestion that the breast cancer benefit from tamoxifen 
could be greater in women over age 50, but older women are also at 
increased risk for some of the serious side effects (endometrial 
cancer, pulmonary embolism, and deep vein thrombosis).
    Women on tamoxifen also had fewer diagnoses of noninvasive breast 
cancer, such as ductal carcinoma in situ (31 cases in the tamoxifen 
group versus 59 cases in the placebo group). Eight participants have 
died of breast cancer, three in the tamoxifen group and five in the 
placebo group.
    ``This advance represents the results of a long-term investment in 
research,'' said NCI Director Richard Klausner, M.D. ``This is a real 
advance, but it is no magic bullet. Only through continued research 
will we find preventions that are even more effective and with fewer 
side effects.''
    At the inception of the study, the investigators made a commitment 
to notify study participants of major results prior to any public 
announcement. The BCPT Participant Advisory Board, a group of 16 women 
in the trial, was notified by conference call. Letters were sent to 
BCPT researchers, and they in turn mailed letters or made other plans 
to notify the participants at their sites.
    ``Our heartfelt gratitude is extended to the study participants,'' 
said Norman Wolmark, M.D., chairperson of NSABP. ``It is only because 
of their commitment that we were able to answer a question of extreme 
importance to many women.''
    Sandy Kanicki, co-chair of the Participant Advisory Board, said 
simply, ``The results are so profound that I'm speechless. We don't 
know where we are going to go from here but we have taken a major step 
to help women reduce their incidence of breast cancer.''
    Women in the study will continue to be monitored by BCPT 
investigators. Post menopausal women who had been taking the placebo 
may have the option to participate in an upcoming trial that will 
compare tamoxifen to another drug that could have similar breast cancer 
prevention properties, but which might be associated with fewer adverse 
effects. Women of any age on placebo also have the option of seeking 
tamoxifen from their health care providers.
    The BCPT researchers will be evaluating the study's results in 
great detail in coming weeks. The final analysis will be published in 
the scientific literature.
    The study began recruiting, participants in April 1992 and closed 
enrollment in September 1997. Researchers with the NSABP are conducting 
the study in more than 300 centers across the United States and Canada.
    ``Since 1990 when I and my NSABP colleagues, together with members 
of NCI, designed this study, there has been an unprecedented display of 
teamwork by the participants, their physicians, study support staff, 
numerous government agencies, and medical centers,'' said Bernard 
Fisher, M.D., scientific director at NSABP. ``That commitment to 
scientific investigation has resulted in this landmark accomplishment. 
I am delighted to have had an opportunity to make a contribution.''
    Only women at increased risk for developing breast cancer 
participated in the study. Because the risk of breast cancer increases 
with age, women 60 years of age and older qualified to participate 
based on age alone. At age 60, about 17 of every 1,000 women are 
expected to develop breast cancer within five years. Women between the 
ages of 35 and 59 who demonstrated an increased risk of breast cancer 
equivalent to or greater than that of an average 60-year-old woman were 
also eligible. This breast cancer risk was determined by a computer 
calculation based on the following factors:
  --Number of first-degree relatives (mother, daughters, or sisters) 
        who had been diagnosed as having breast cancer;
  --Whether a woman had any children and her age at her first delivery;
  --The number of times a woman had had breast lumps biopsies 
        especially if the tissue was shown to have a condition known as 
        atypical hyperplasia;
  --The woman's age at her first menstrual period.
  --Whether a woman had had a type of noninvasive breast cancer known 
        as lobular carcinoma in situ.
    One of the most widely prescribed cancer drugs in the worlds 
tamoxifen has been the focus of more than 25 years of research on its 
actions, benefits, and risks. Zeneca Pharmaceuticals, Wilmington, Del., 
manufactures tamoxifen and provided both the drug and placebo pills for 
the prevention study without charge.
    For information on the BCPT and easy access to all clinical trials 
information from NCI, go to: http://cancertrials.nci.nih.gov
    For information on NSABP clinical trials, including, future 
prevention trials, go to: http://www.nsabp.pitt.edu
    The National Cancer Institute's Cancer Information Service (CIS) is 
a nationwide information and education network for cancer patients and 
their families, the public, and health professionals. The CIS can 
provide information about breast cancer prevention, detection, 
treatment, and research. One toll-free number, 1-800-4-CANCER (1-800-
422-6237) connects English- and Spanish-speaking callers all over the 
country with the office that serves their area. The number for callers 
with TTY equipment is 1-800-332-8615.
                                 ______
                                 
   Questions and Answers: Preliminary Results From the Breast Cancer 
                            Prevention Trial
                      background and study design

What is the breast cancer prevention trial?
    The Breast Cancer Prevention Trial (BCPT) is a clinical trial (a 
research study conducted with people) designed to see whether taking 
the drug tamoxifen (Nolvadex) can prevent breast cancer in 
women who are at an increased risk of developing the disease. The BCPT 
is also looking at whether taking tamoxifen decreases the number of 
heart attacks and reduces the number of bone fractures in these women. 
The study began recruiting participants in April 1992 and closed 
enrollment in September 1997; 13,388 women ages 35 and older are 
enrolled. Researchers with the National Surgical Adjuvant Breast and 
Bowel Project (NSABP) are conducting the study in more than 300 centers 
across the United States and Canada. The study is funded by the 
National Cancer Institute (NCI), the United States' primary agency for 
cancer research.

What is tamoxifen?
    Tamoxifen is a drug, taken by mouth as a pill. It has been used for 
25 years to treat patients with advanced breast cancer. Since 1985 it 
has also been recommended in the United States for adjuvant, or 
additional, therapy, following surgery and/or radiation for early stage 
breast cancer. Tamoxifen works against breast cancer, in part, by 
interfering with the activity of estrogen, a female hormone that 
promotes the growth of breast cancer cells. For this reason, tamoxifen 
is often called an ``anti-estrogen.'' In treatment, the drug slows or 
stops the growth of these cancer cells.

Why was tamoxifen tested to prevent breast cancer?
    Research has shown that taking tamoxifen as adjuvant therapy for 
breast cancer not only helps prevent the original breast cancer from 
returning but also helps to prevent the development of new cancers in 
the opposite breast. Researchers believed that tamoxifen might have a 
similar beneficial effect for women at increased risk of breast cancer. 
While tamoxifen acts against the effects of estrogen in breast tissue, 
it acts like estrogen in other body systems. Tamoxifen's estrogen-like 
effects include the lowering of blood cholesterol and the slowing of 
bone loss that may lead to osteoporosis and bone fractures.

Who participated in the BCPT?
    Women at increased risk for developing breast cancer participated 
in the study. These included women 60 years of age and older who 
qualified to participate based on age alone, and women between the ages 
of 35 and 59 with an increased risk of breast cancer equivalent to or 
greater than that of a 60 year old woman. At age 60, about 17 of every 
1,000 women are expected to develop breast cancer within five years.
    Of the 13,388 women on the trial, about 40 percent were ages 35 to 
49, about 30 percent were ages 50 to 59, and about 30 percent were age 
60 or older. About 3 percent of the participants were minorities, 
including African American, Asian American, Hispanic, and other groups.

Did every woman in the study receive tamoxifen?
    No. Participants in the BCPT were randomized (selected by chance) 
to receive either tamoxifen or a placebo (an inactive pill that looked 
like tamoxifen). In a process known as ``double blinding,'' neither the 
participant nor her physician knew which pill she was receiving. 
Setting up a study in this way allowed the researchers to clearly see 
what the true benefits and side effects of tamoxifen are without the 
influence of other factors. According to the design, all women in the 
study were to take two pills a day for five years, either a 20-mg dose 
of tamoxifen (two 10-mg pills) or placebo pills.

Why were women 60 years of age or older eligible for the BCPT based on 
        age alone?
    Many diseases, including breast cancer, occur more often in older 
persons. The risk of developing breast cancer increases with age, so 
breast cancer occurs more commonly in women over 60 years of age. The 
risk of developing heart disease or osteoporosis also increases with 
age, and those diseases are also being studied in the BCPT.

What factors were used to determine increased risk of breast cancer for 
        the participants aged 35 to 59?
    To enroll in the study, women between 35 and 59 years of age needed 
to have a risk of developing breast cancer within the next five years 
that was equal to or greater than the average risk for 60-year-old 
women. This increased risk was determined in one of two ways. Women 
diagnosed as having lobular carcinoma in situ, a condition that is not 
cancer but indicates an increased chance of developing invasive breast 
cancer, were eligible based on that diagnosis alone. The risk for other 
women was determined by a computer calculation based on the following 
factors:
  --Number of first-degree relatives (mother, daughters, or sisters) 
        who had been diagnosed as having breast cancer;
  --Whether a woman had any children and her age at her first delivery;
  --The number of times a woman had had breast lumps biopsied, 
        especially if the tissue was shown to have a condition known as 
        atypical hyperplasia; and
  --The woman's age at her first menstrual period.
    For example, a 35-year-old woman would have to have two or more 
first-degree relatives with breast cancer AND a personal history of at 
least one benign breast biopsy, OR a diagnosis of lobular carcinoma in 
situ.
    A 45-year-old woman would have to have one or more first-degree 
relatives with breast cancer AND a personal history of at least one 
benign breast biopsy, OR a diagnosis of lobular carcinoma in situ.
    A 55-year-old woman would have to have one or more first-degree 
relatives with breast cancer OR a personal history of at least one 
benign breast biopsy OR a diagnosis of lobular carcinoma in situ.
What proportion of women in the United States are estimated to be at 
        the level of risk required for participation in the BCPT?
    At age 35, about three women in 1,000 would have qualified for the 
study based on their estimated breast cancer risk or 0.3 percent.
    At age 40, the proportion is about 27 women in 1,000, or 2.7 
percent.
    At age 45, the proportion is about 71 women in 1,000, or 7.1 
percent.
    At age 50, the proportion is about 93 women in 1,000, or 9.3 
percent.
    At age 55, the proportion is about 125 women in 1,000, or 12.5 
percent.
    At age 60 and beyond, all women would have met the breast cancer 
risk criteria.
Did other factors affect eligibility for the study?
    Certain existing health conditions affected eligibility for the 
study. For example, women at increased risk for blood clots could not 
participate. Also, women taking hormone replacements and women using 
oral contraceptives (``the pill'') could not take part in the trial 
unless they stopped taking these medications. Those who stopped taking 
these hormones were eligible for the study three months after they 
discontinued the drugs.
    Women who were pregnant or who planned to become pregnant were not 
eligible to participate. Animal studies have suggested that the use of 
tamoxifen during pregnancy might harm the fetus. Premenopausal women 
participating in the BCPT were required to use some method of birth 
control other than oral contraceptives. Oral contraceptives may change 
the effects of tamoxifen and may also affect the risk of breast cancer.
Were the participants required to have any medical exams?
    Participants were required to have blood tests, a pelvic exam, a 
mammogram, and a physical exam before being accepted into the study. 
Women 55 years of age and older needed to have an electrocardiogram or 
ECG (a test to measure the heart's muscular activity), in addition to 
the other tests. Screening endometrial sampling (an examination of 
cells from the lining of the uterus) was required at entry for 
participants joining the study beginning in October 1994 and was 
strongly recommended annually for all women in the study. These tests 
were repeated periodically.

Who paid for these medical exams?
    Most physicians' fees and the costs of medical tests were charged 
to the participant as if she were not part of the study; however, the 
costs for these tests were often covered by the participant's insurance 
company. Screening endometrial samplings were provided without charge. 
For women over 55, the required electrocardiograms were also done at no 
cost. Every effort made to contain the costs specifically associated 
with participation in this study.
How much did the tamoxifen cost the participants?
    There was no charge to participants for the tamoxifen or the 
placebo. The company that manufactures tamoxifen, Zeneca 
Pharmaceuticals Group, of Wilmington, Del., (formerly ICI Americas, 
Inc.) provided both the tamoxifen and the placebo without charge.

                PRELIMINARY TRIAL RESULTS/NOTIFICATIONS

What are the initial results of the BCPT?
    At this point (data to Jan. 31, 1998), women on the trial have been 
followed on the study for about four years. Results show 45 percent 
fewer diagnoses of invasive breast cancer in women who were randomized 
to take tamoxifen compared to women who were randomized to take the 
placebo (85 cases in the tamoxifen group versus 154 cases in the 
placebo group). Women on tamoxifen also had fewer diagnoses of 
noninvasive breast cancer, such as ductal carcinoma in situ (31 cases 
in the tamoxifen group versus 59 cases in the placebo group). Eight 
women have died of breast cancer, three women in the tamoxifen group 
and five women in the placebo group.
    Women in the tamoxifen group had fewer bone fractures than women in 
the placebo group (47 cases in the tamoxifen group versus 71 cases in 
the placebo group). There was no difference in the number of heart 
attacks between the two groups.
    Tamoxifen did increase the women's chances of three rare but 
serious health problems: endometrial cancer (cancer of the lining of 
the uterus) 33 cases in the tamoxifen group versus 14 cases in the 
placebo group; pulmonary embolism (blood clot in the lung) 17 cases in 
the tamoxifen group versus 6 cases in the placebo group; and deep vein 
thrombosis (blood clots in major veins) 30 cases in the tamoxifen group 
versus 19 cases in the placebo group.

What were the participants' chances of developing endometrial cancer?
    BCPT participants who were randomized to the tamoxifen group had 
more than twice the chance of developing endometrial cancer compared 
with women on placebo (based on 33 cases in the tamoxifen group versus 
14 cases in the placebo group). The increased risk of endometrial 
cancer was equal to the risk that was expected and is in the same range 
as (or less than) the endometrial cancer risk for postmenopausal women 
taking single-agent estrogen replacement therapy. Estrogens and agents 
that act like estrogens are known to increase the risk of endometrial 
cancer.
    All the participants were informed about the possibility of 
increased risk of endometrial cancer before they entered the study. 
Like all cancers, endometrial cancer is potentially life-threatening. 
All but one (in the placebo group) of the endometrial cancers that 
occurred during the study were found at an early stage, when treatment 
is very effective. However, one participant (also in the placebo group) 
died of endometrial cancer. About 37 percent of BCPT participants in 
both groups had a hysterectomy (surgery to remove the uterus) for a 
variety of health reasons before joining the study. Therefore, these 
women were not at any risk for endometrial cancer.

What was done to help diagnose endometrial cancer early?
    Pap smears are very effective at detecting cancer in the cervix but 
are not useful for detecting endometrial cancer. Therefore a screening 
endometrial sampling--removal of cells in the lining of the uterus for 
examination under a microscope--was used in the BCPT to detect 
abnormalities in the endometrium. Women who joined the study after 
October 1994 were required to have a screening endometrial sampling 
before entering the study if their uterus had not been removed. All 
women in the study were strongly urged to have screening endometrial 
sampling done annually throughout the study (at no cost to them), but 
could decline if they chose. In addition to these annual tests, women 
in the BCPT were told to see their physicians if they experienced 
abnormal vaginal bleeding or pain. The vast majority of the endometrial 
cancers that were diagnosed in the BCPT caused such symptoms.
What were the participants' chances of getting blood clots?
    Women taking tamoxifen had almost three times the chance of 
developing a pulmonary embolism (blood clot in the lung) as women on 
placebo (based on 17 cases in the tamoxifen group versus 6 cases in the 
placebo group). Two women died from these embolisms, both in the 
tamoxifen group. Women in the tamoxifen group were also more likely to 
have deep vein thrombosis (a blood clot in a major vein) than women on 
placebo (30 cases versus 19 cases). Blood clots occur more often in 
people with high blood pressure (hypertension), diabetes, smokers, and 
in those who are obese.

Is there a relationship between tamoxifen use and the development of 
        eye problems?
    Women in the tamoxifen group, in general, had no more eye problems 
than women taking the placebo. However, women taking tamoxifen may be 
at a slightly increased risk for developing cataracts (a clouding of 
the lens inside the eye) according to other research.
    As women age, they are more likely to develop cataracts whether or 
not they take tamoxifen. Other eye problems, such as corneal scarring 
or retinal changes, have been reported in a few breast cancer patients 
in tamoxifen treatment trials.

Was tamoxifen associated with any other cancers?
    Tamoxifen was not associated with an increased risk of any other 
cancer other than endometrial cancer.

What were the other adverse effects of tamoxifen?
    Like most medications, whether over-the-counter medications, 
prescription drugs, or drugs in research studies, tamoxifen causes 
adverse effects in some women. The effects experienced most often by 
women in the tamoxifen group were hot flashes and vaginal discharge. 
Women in both groups reported sometimes having side effects--even 
though the placebo itself would not cause any symptoms. The side 
effects that some women in both groups reported included: vaginal 
dryness, itching, or bleeding; menstrual irregularities; depression; 
loss of appetite; nausea and/or vomiting; dizziness; headaches; and 
fatigue. Treatments that could minimize or eliminate most side effects 
were available to the participants.

Did any group of women benefit more from tamoxifen than others?
    It is possible that the breast cancer benefit from tamoxifen could 
be greater in women over age 50, but older women are also at increased 
risk for some of the serious side effects (endometrial cancer, 
pulmonary embolism, and deep vein thrombosis).

Why was the study ``unblinded,'' and who made that decision?
    As part of the study design, the BCPT data were regularly reviewed 
by an independent Endpoint Review, Safety Monitoring, and Advisory 
Committee (ERSMAC). At its regularly scheduled meeting on March 24, 
1998, the committee recommended to NSABP that the study be unblinded 
(inform the participants and their physicians what pills the 
participants had been taking) because of the clear evidence of a 
reduction of breast cancer incidence in the tamoxifen group. The NSABP 
presented the data and recommendation to the NCI on March 26 and 
together, NSABP and NCI researchers concurred with the committee's 
recommendation. This was based upon the assessment of all three groups 
that the effect of tamoxifen in the reduction of breast cancer had been 
demonstrated. It was agreed that any additional information that could 
be gained from continuing the study in its current form did not 
outweigh the benefits of making the treatment available to the 
participants in the placebo group and other women at an increased risk 
of breast cancer.

How were the participants notified?
    At the inception of the study, the NSABP made a commitment to make 
every effort to notify the participants of major results prior to any 
public announcement. After notification to the BCPT Participant 
Advisory Board, a group of 16 women in the trial, a letter announcing 
initial results, and details for participant ``unblinding'' was rapidly 
sent to BCPT investigators so that they could convey this information 
to BCPT participants.

What will the participants do now?
    All participants are being asked to continue with their follow-up 
examinations. Women who have been randomized to the tamoxifen group who 
have not completed five years of tamoxifen therapy will have the 
opportunity to continue on therapy. Postmenopausal women who had been 
taking the placebo are being invited to participate in an upcoming 
trial that will compare tamoxifen to a different drug that could have 
similar breast cancer prevention properties, but might be associated 
with fewer adverse effects. Women of any age on placebo also have the 
option of seeking tamoxifen from their private health care providers.

Would it be beneficial for women to take tamoxifen for more than five 
        years?
    Not necessarily: Results of another NSABP study in which women with 
early stage breast cancer took tamoxifen for 5 years versus 10 years 
(called the B-14 trial) showed no greater benefit from the longer 
duration of tamoxifen and showed a trend toward more adverse effects.

                            PUBLIC CONCERNS

Was any special effort made to include minority women on the trial?
    Throughout the trial, several strategies were used to increase 
participation of women from racial and ethnic minority groups. These 
strategies included placing study-related recruitment materials in 
businesses and churches located in minority communities; collaborating 
with a minority-owned public relations firm to develop a structured 
media campaign targeting racial and ethnic minorities; developing and 
broadly disseminating a Public Service Announcement that featured 
singer Nancy Wilson; and communicating information to study sites about 
how other sites successfully reached racial and ethnic minorities.
    When the early strategies did not attract sufficient numbers of 
minority participants, the NSABP launched the Pilot Minority 
Recruitment Program in August 1996. The goal of the program was to 
increase participation by increasing awareness and educating minority 
populations about the trial. A multidimensional approach was used: 
Community Outreach Coordinators employed at five BCPT sites offered 
personalized presentations on breast cancer risk factors, incidence, 
and survival rates, and on clinical trial research at African American 
churches, community hospitals and health clinics, health fairs, public 
housing sites, businesses, and local chapters of sororities, the Urban 
League, and minority medical societies. In less than a year, these 
strategies enabled the coordinators to establish many relationships in 
their communities. As a result of these efforts, the number of Risk 
Assessment Forms submitted by minority groups increased, and during 
this period, the BCPT experienced the highest level of randomizations 
from racial and ethnic minority groups since the trial began. The Pilot 
Minority Recruitment Program has been the most effective strategy to 
date and will serve as the model for minority recruitment for future 
prevention trials.

Will the study results be published?
    Further analyses of the data are under way. A manuscript will be 
prepared and submitted to a peer-reviewed journal.

Based on the BCPT results, should women who are at increased risk of 
        breast cancer take tamoxifen?
    Women who are at increased risk of breast cancer now have the 
option to consider taking tamoxifen to reduce their chances of 
developing breast cancer. As with any medical procedure or 
intervention, the decision to take tamoxifen is an individual one in 
which the benefits and risks of the therapy must be considered. The 
balance of these benefits and risks will vary depending on a woman's 
personal health history and how she weighs the benefits and risks. 
Therefore even if a woman is at increased risk of breast cancer, 
tamoxifen therapy may not be appropriate for her. Women who are 
considering tamoxifen therapy should talk with their health 
professional.

How can a woman learn more about the next breast cancer prevention 
        trial?
    The NSABP is planning a new breast cancer prevention trial, 
tentatively scheduled to begin in fall 1998. The trial would involve 
postmenopausal women who are at least 35 years old and are at increased 
risk for developing breast cancer. The study would compare tamoxifen to 
another drug.
    There are several ways to be placed on a mailing list for more 
information on this upcoming trial--by Internet, by mail, or by fax. On 
the Internet, the NSABP homepage (www.nsabp.pitt.edu) has a form 
available. By regular mail, send a letter or post card with name, 
mailing address, and a note specifying interest in future breast cancer 
prevention trials to: NSABP, Box 21, Pittsburgh, PA, 15261. Or fax the 
same information to NSABP at 412-330-4664. When information about the 
next prevention trial is available, it will be mailed to the people on 
this list.

How does a woman determine whether she is at increased risk of breast 
        cancer?
    BCPT participants had their risk for developing breast cancer 
calculated using age, family history, and medical information in a 
computer program that also estimated their likelihood of developing 
heart disease, endometrial cancer, and blood clots. Some private 
physicians use computer calculations in their practice to assess breast 
cancer risk, but because these are not identical to the program used in 
the BCPT, it is unclear how well those programs would identify women at 
increased risk. The NSABP and NCI plan to make information available 
which will assist a woman and her health care provider to determine 
whether her risk is comparable to the women who participated in the 
BCPT.

Will women with breast cancer gene alterations (BRCA1 and BRCA2) 
        benefit from tamoxifen?
    These two breast cancer gene alterations, which increase a woman's 
risk of the disease, were first identified after the BCPT began. Using 
blood samples taken from participants, analyses are under way to 
determine whether tamoxifen has the same relative effects on women 
whether or not they carry alterations in these genes. To maintain 
strict confidentiality, samples in this study have no identifying 
labels that could link them to individual women. Therefore, researchers 
will not be able to give individual results to a participant or her 
health care provider.
Is tamoxifen a good substitute for hormone replacement therapy?
    No. Every woman has individual health risks that affect her need 
for interventions such as hormone replacement therapy or tamoxifen 
therapy. Hormone replacement therapy is intended to help women maintain 
bone density. It may also reduce the risk of heart disease in 
postmenopausal women, and many women benefit from a reduction in hot 
flashes and other problems that can affect quality of life. Some 
studies have suggested that hormone replacement therapy increases a 
woman's chances of developing breast cancer.
    The BCPT results show that tamoxifen reduces breast cancer risk and 
may help slow or reduce bone loss, as evidenced by the reduced number 
of hip fractures, but it did not decrease heart disease risk. A woman 
with a large risk of heart disease but no increased risk of breast 
cancer may not have the same benefit from tamoxifen as from hormone 
replacement therapy.

Should women who are not at a demonstrated increased risk of breast 
        cancer consider taking tamoxifen?
    This question has not been studied. At this time, there is no 
evidence that tamoxifen is beneficial for women who do not have an 
increased risk of breast cancer.

Are there any women who should not take tamoxifen?
    Animal studies have suggested that the use of tamoxifen during 
pregnancy might harm the fetus. Women who were pregnant or who planned 
to become pregnant were not eligible to participate in the BCPT. 
Premenopausal women participating in the BCPT were required to use some 
method of birth control other than oral contraceptives (``the pill'') 
while taking tamoxifen. Oral contraceptives and hormone replacement 
therapy may change the effects of tamoxifen and may also affect the 
risk of breast cancer.
    Women with a history of blood clots, hypertension, diabetes, and 
cigarette smoking must also consider that tamoxifen increases the risk 
for serious blood clots.
How much does a standard dose of tamoxifen cost?
    A month's supply of tamoxifen costs about $80 to $100.
How much did the study cost?
    The trial had been projected to cost $70 million, but the total 
cost is estimated at $50 million, including $10 million for two more 
years of followup. All except $3.5 million from the National Heart, 
Lung, and Blood Institute, was provided by NCI.
Why is the breast cancer prevention trial so important?
    This year, more than 178,000 women in the United States alone will 
be diagnosed as having breast cancer, and about 43,500 will die of the 
disease. For many years, women at increased risk for developing breast 
cancer had no proven means to reduce their risk. Women had to rely on 
frequent checkups and periodic mammograms to detect breast cancer at an 
early stage. Doctors sometimes suggest that certain women at very high 
risk have preventive (prophylactic) mastectomies, which is surgery to 
remove breast tissue before cancer develops. However, the operation 
does not guarantee that breast cancer will be avoided, because it is 
almost impossible to remove all the breast tissue and the impact of 
prophylactic mastectomy on breast cancer risk is not known.
    Because tamoxifen was successful in reducing the incidence of 
breast cancer, women at increased risk for developing the disease will 
have a choice other than more frequent exams or major surgery (although 
regular mammography should continue even if a woman decides to use 
tamoxifen). In order to prove its value, tamoxifen had to be tested in 
a large research study to determine whether the benefits outweighed the 
risks.
What is the national surgical adjuvant breast and bowel project?
    The National Surgical Adjuvant Breast and Bowel Project is a 
cooperative group with a 40 year history of designing and conducting 
clinical trials, the results of which have changed the way breast 
cancer is treated, and now, potentially prevented. Results of research 
studies conducted by NSABP researchers have been the dominant force in 
altering the standard surgical treatment of breast cancer from radical 
mastectomy to lumpectomy plus radiation. This group was also the first 
to demonstrate that adjuvant therapy could alter the natural history of 
breast cancer, thus increasing survival rates. When a breast cancer 
prevention study was initially conceived, more than 30,000 women with 
breast cancer had participated in treatment studies conducted by NSABP 
investigators. A research study to prevent breast cancer was a logical 
next step for this research group.
    NSABP was recently incorporated under the aegis of the NSABP 
Foundation, Inc., a Pennsylvania nonprofit membership organization with 
nearly 300 members in the United States, Canada, and Australia. More 
than 6,000 physicians, nurses, and other medical professionals in the 
NSABP located in member institutions and their satellites are involved 
in the conduct of treatment and prevention trials. NCI provides funding 
for the two headquarters components of NSABP: the NSABP Operations 
Center at Allegheny University of the Health Sciences, Allegheny 
Campus, and the NSABP Biostatistical Center at the University of 
Pittsburgh, both located in Pittsburgh, PA. NCI also provides funding 
directly or indirectly, to the medical center Members of the NSABP 
Foundation, Inc., who are responsible for implementation of NSABP 
studies.
    For information on the BCPT and easy access to all clinical trials 
information from NCI, go to: http://cancertrials.nci.nih.gov
    For information on NSABP clinical trials, including future 
prevention trials, go to: http://www.nsabp.pitt.edu
    The National Cancer Institute's Cancer Information Service (CIS) is 
a nationwide information and education network for cancer patients and 
their families, the public, and health professionals. The CIS can 
provide information about breast cancer prevention, detection, 
treatment, and research. One toll-free number, 1-800-4-CANCER (1-800-
422-6237) connects English- and Spanish-speaking callers all over the 
country with the office that serves their area. The number for callers 
with TTY equipment is 1-800-332-8615.
                                 ______
                                 
   NSABP Breast Cancer Prevention Trial (BCPT) Speakers' Biographies
    Norman Wolmark, M.D., is the Chairperson of the National Surgical 
Adjuvant Breast and Bowel Project (NSABP), a cooperative clinical 
trials group funded primarily by the National Cancer Institute. Dr. 
Wolmark is also the Principal Investigator of the NSABP Operations 
Center located on the Allegheny campus of Allegheny University of the 
Health Sciences.
    Dr. Wolmark received his bachelor's and medical degrees from McGill 
University in Montreal, Canada. After completing his surgical residency 
at the University of Pittsburgh, he received additional fellowship 
training in surgical oncology at the National Cancer Institute in 
Bethesda, Maryland, and at the Memorial Sloan-Kettering Cancer Center 
in New York City, New York. He is currently Professor and Chairman of 
the Department of Human Oncology at Allegheny University of Health 
Sciences.
    D. Lawrence Wickerham, M.D., has been the Associate Chairman of the 
NSABP since 1995 and is the Protocol Officer for the Breast Cancer 
Prevention Trial. As the Protocol Officer, Dr. Wickerham oversees the 
conduct and medical review of the protocol and coordinates committee 
activities. Dr. Wickerham has worked for the NSABP in several 
capacities since 1981.
    Dr. Wickerham received his bachelor's degree from Washington and 
Jefferson College in Washington, Pennsylvania, and received his medical 
degree from the University of Pittsburgh. He is also currently an 
Associate Professor of Human Oncology at the Allegheny campus of the 
Allegheny University of the Health Sciences.
    Bernard Fisher, M.D., is a founding member and former chairperson 
of the NSABP from 1967 to 1994. He has devoted his career to exploring 
the biology of cancer and providing new treatments for women with 
breast cancer. Dr. Fisher's laboratory and clinical investigations have 
resulted in major alterations in the use of surgery and systemic 
therapy for breast cancer management.
    Beginning in 1990, Dr. Fisher and his NSABP colleagues, working 
with the NCI and numerous government agencies, designed and implemented 
the first breast cancer prevention trial in the United States. In 
addition to determining the value of tamoxifen in breast cancer 
prevention, the study was to be directed toward addressing questions 
related to the genetics of the disease. Dr. Fisher is past-president of 
the American Society of Clinical Oncology and a former member of both 
the President's Cancer Panel and the National Cancer Advisory Board. He 
is currently Scientific Director of the NSABP and professor at the 
Allegheny campus of the Allegheny University of the Health Sciences.
    H. Samuel Wieand, Ph.D., has been the Director of the NSABP 
Biostatistical Department since 1995. He is also a Professor in and the 
Associate Chairman of the Department of Biostatistics at the University 
of Pittsburgh. Prior to joining the NSABP, he was Director of 
Biostatistics of the Mayo Clinic Cancer Center and of the North Central 
Cancer Treatment Group (NCCTG).
    Dr. Wieand received his Ph.D., from the University of Maryland in 
1974. He is a Fellow of the American Statistical Association.
    Joseph Costantino, Dr. P.H., is the Associate Director of the NSABP 
Biostatistical Center and the Coordinating Statistician of the NSABP 
Breast Cancer Prevention Trial. He is also an Associate Professor of 
Biostatistics at the University of Pittsburgh's Graduate School of 
Public Health. Dr. Costantino has been with the NSABP and the 
University of Pittsburgh since 1984. Before joining the NSABP, he was 
employed as the Director of Health Effects Research for the BCR 
National Laboratory. Prior to this position, he was the Deputy Director 
of the Allegheny County Health Department in Pittsburgh, Pennsylvania.
    Dr. Costantino received his bachelor's degree from Bethany College 
in Bethany, West Virginia and his doctoral degree from the University 
of Pittsburgh in Pittsburgh, Pennsylvania.
                                 ______
                                 
                 Biographical Sketch of Elsie Anderson
    I am now finished with my 5 years on the tamoxifen/placebo Breast 
Cancer Prevention Trial. When you are told that you will be on this 
trial for 5 years, it seems so long, but the years have gone by so 
quickly. I am so happy that I never gave up. I had one breast tumor 
removed and a needle biopsy during the trial; neither were malignant. I 
also had other illnesses, not due to tamoxifen (if that is what I was 
on), but mostly due to my age, such as thyroid disease and colitis. My 
breast surgeon did not approve of this trial, and neither did the 
mammogram technician. Both firmly told me their opinions, but because 
someone has to take a stand, as others have before me and others will 
after me, why not me? We all have responsibilities and I believe ``I am 
my brother's keeper.'' Because my three daughters have lost one aunt 
and two sisters to cancer (one to breast cancer), and have another aunt 
who is a survivor of breast cancer, and I have eight granddaughters who 
are at high risk and many friends who have breast cancer, and because 
of the knowledge of what my two grandchildren have had to go through 
because they had no mom, I would go on another trial if possible. I 
don't want to see any more moms who have to leave their children behind 
as they face death.
    I have been appreciated and looked after so well by the NSABP 
staff, and also by our local cancer clinic. I have had the best care 
possible. Thank you everyone.
    I believe we have to prevent cancer besides finding a cure, and I 
have had the opportunity to do that.
                                 ______
                                 
               Biographical Sketch of Judith Ann Bingham
    I was born at Baptist Hospital in New Orleans, Louisiana on 
Tuesday, July 10, 1951. I have three sisters and three brothers. 
Throughout my school years, I enjoyed singing in the church choir and 
teaching roller skating lessons for the Jefferson Parish Recreation 
Department.
    From 1969 to 1997, I worked at Sears Roebuck and Co. I am currently 
a Collection Supervisor for First Commerce Corporation. In 1976, I 
married Donald Bingham, and we currently reside in Slidell, Louisiana. 
We don't have children, but we have 8 nieces and 9 nephews.
    I enjoy bowling, skating, walking, arts and crafts, shopping, and 
collecting koala bears of any shape, size, or form. I also enjoy 
helping others, and that is one of the reasons I decided to participate 
in the BCPT. I am committed to the study and its success.
                                 ______
                                 
                Biographical Sketch of Barbara Capuzelo
    I am originally from southwestern Pennsylvania and moved to Kansas 
City, Missouri in 1980 after having lived in Washington DC, Los 
Angeles, New York, and Boston. I became a single parent in 1982 of a 
10-year old girl. When I realized that I was her sole support, and that 
I was in a dead-end job, I decided to pursue my childhood dream of 
becoming a nurse. I graduated from Avila College with a BSN and many 
honors, with a job waiting at the local Veterans Administration. I 
stayed there until 1993 when I moved to St. Luke's in June. Since then, 
I have served as Chair of the Unit-based Education Committee and am 
presently co-chair of the Unit-based Quality Committee. I work on a 
medical-surgical oncology, blood and transplant unit, I am active in 
the local and national chapters of the Oncology Nursing Society, and I 
am a Eucharistic minister and rector at my parish. I have completed a 
three year New Wine Program and am presently pursuing a master's degree 
in clinical counseling.
    I am very proud of raising an independent daughter, who has made me 
a mother-in-law and grandmother of a 10-month old baby girl. I have two 
cats, love dogs, cry at sad movies, like to travel (I worked for TWA in 
Los Angeles) and meet people, read, enjoy the theater, and love ice 
cream. I have been a BCPT participant since October 1993.
                                 ______
                                 
                Biographical Sketch of Mary Ellen Gorman
    Two words that summarize my life are competitive and generalist. I 
do many things well but am an expert at nothing! Over the years I have 
been a full-time mom to three daughters, divorced, single working 
parent, remarried, retail business partner with my spouse and finally a 
ski instructor! I have always enjoyed competing in sports from tennis, 
to ski racing, to indoor rowing. Skiing is my bliss! Now we are retired 
and enjoy the outdoor life of Montana. Other hobbies we enjoy together 
are cooking, collecting wine, and classical music.
    I am very fortunate, as my father is approaching his 100th birthday 
and my mother, age 93, is a 33-year breast cancer survivor. I consider 
it a privilege to be a participant in the BCPT. It raised my knowledge 
and commitment to many breast cancer issues. I feel very rewarded by my 
advocacy work, both locally and nationally, for this most important 
clinical trial.
                                 ______
                                 
               Biographical Sketch of Sandra Kay Kanicki
    I am the mother of four sons and I have four daughters-in-law. I 
serve on the school board, and participate in breast cancer awareness 
activities in my community. The catalyst to my participating in this 
very important trial was that my grandmother, mother, and sister are 
all 8-year survivors of breast cancer. My number one priorities are my 
husband and my family, and I believe that I have contributed greatly to 
future generations by participating in this trial.
                                 ______
                                 
              Biographical Sketch of Elizabeth (Betty) Lee
    I was born in Huntingdon, West Virginia and was the 7th daughter 
and 11th child of the late Pearl William and Luana Dortch Adams. My 
family migrated to Syracuse, New York in the late 40's for a visit, and 
remained. I am married to Fred Lee, and together we have four children, 
14 grandchildren, and one great-grandson. I am a 1995 Syracuse 
University Master's of Social Work graduate. While working on my 
degree, I became the first humble and proud winner of the Vivian Teall 
Howard (former first lady of Hopps Memorial C.M.E. Church) Graduate 
Student Award. Prior to my entry to graduate school, (May, 1994) I 
retired from 25 years of public service. However, I completed most of 
my college education while working full-time and raising a family, and 
have started a second career with the Syracuse Community Health Center 
as a certified social worker in the capacity of counselor/therapist.
    Because my spiritual life is of the utmost importance to me, I am 
active in Hopps Memorial Church where I am a 50-year plus member and 
perform many duties ranging from Church clerk to a member of the Gospel 
Chorus and president of the Missionary Society. I am also an active 
member of the 6th District Prince Hall Masonic Family.
    I thank God for His grace, my husband, children, and other family 
members and friends for their love and support and intend to continue 
working for the betterment of mankind as long as God sees fit to use 
me, and being in this trial is one of the ways I feel He has chosen to 
use me.
                                 ______
                                 
                 Biographical Sketch of Jeannie Morice
    To my closest friends, I am considered outgoing, fun-loving, and a 
little eccentric--I attribute all the above to my Irish Catholic 
upbringing. My Canadian-born husband Dale and I have survived 27 years 
of marriage with never a dull moment. Dale is a Scorpio and yours truly 
a Leo. Our three children, ages 21 to 25, currently attend University. 
Hopefully, with a decent education, we can enjoy the true meaning of 
``empty nesters.'' We love Calgary, Alberta and being close to the 
beautiful Rockies. My hobbies include wine making, tai-chi, and walking 
my gorgeous golden retriever, Murphy.
    I joined the BCPT having lost my mother to breast cancer. I remain 
confident that the results of this trial will benefit not only myself, 
but my daughters and women everywhere.
                                 ______
                                 
                  Biographical Sketch of Beverly Munn
    I am the mother of three and grandmother of four. My mother had 
breast cancer for 10 years before she passed away in 1991. My sister 
and only sibling has had two separate incidences of breast cancer. This 
is why I am a high-risk participant. I work part-time as a secretary in 
a doctor's office. I enjoy traveling and antiques.
    My reason for entering the program is to help in the research for 
breast cancer so that the information gained might be of help, not only 
to me, but to future generations of women. I am grateful for the 
opportunity this trial has given me.
                                 ______
                                 
                  Biographical Sketch of Rici Rutkoff
    My mother, grandmother, and two aunts died from breast cancer. I 
have had several close friends develop the disease--some with a family 
history; others without. Breast cancer truly does not discriminate.
    I live in Rockville, Maryland with my family and am a coordinator 
for The Event Network, a Washington, DC, destination management 
company. Being part of the BCPT and any future similar clinical trials 
is my way of being involved in helping to find a prevention for breast 
cancer rather than just waiting to develop it. The experience has been 
exciting and extremely rewarding. I sincerely encourage others that fit 
within the participant criteria to be part of future trials.
                                 ______
                                 
                Biographical Sketch of Mary Sankolewicz
    I am currently in the process of moving back to Easthampton, 
Massachusetts from a small town in Northern Maine where I have lived 
for the last 2 years. I am a grandmother to a beautiful 4-month old 
baby girl named Tia-Lynn. I have studied early childhood education and 
taught nursery school. My last job I was employed as a personal care 
attendant. I found working with numerous clients very rewarding. I had 
considered entering a nursing program so I could do private duty 
nursing, at one point in my life. Unfortunately, I was in a car 
accident almost 4 years ago which left me disabled and altered my 
future plans in the nursing profession.
    The accident has not affected my commitment to the trial though. 
Personally, I joined the BCPT because breast cancer runs in my family. 
It is my hope that my involvement in the study will benefit my daughter 
and granddaughter so they will not go through the endless worrying and 
wondering.
                                 ______
                                 
                   Biographical Sketch of Marty Smith
    I am a licensed property/casualty insurance agent who enjoys live 
theater, writing, and cross country skiing. I have a 19 year old son, 
and have been married for 25 years. My sister died last year of breast 
cancer. My mother is a breast cancer survivor. I feel there is a 
tremendous need for cancer prevention, and encourage every woman to 
keep an open mind, and never stop looking for breast cancer prevention 
and a cure.
                                 ______
                                 
                 Biographical Sketch of Lonnie Williams
    I am a native Oklahoman. I have been married to the same man for 49 
years. My hobbies are golf, aerobics, bridge, crossword puzzles, and 
reading. I have a B.A. degree from Oklahoma State University. I worked 
as a Service Representative for Southwestern Bell Telephone Company for 
4 years after graduation. Since my children were born, my activities 
have been strictly volunteerism. These included various PTA offices, as 
well as president of our high school PTA. I spent 5 years on the 
woman's committee of the Oklahoma City Symphony. I spent 13 years as 
head of a box office committee for the Oklahoma City Lyric Theater. I 
served on the board of the American Cancer Society for 15 years. I am a 
member of the D.A.R. My daughter was a doctor and I acted as the office 
manager once a week.
    I became a participant in the BCPT in 1992 because my daughter was 
diagnosed with breast cancer at age 35. I was not aware until then how 
many young women were getting breast cancer and how devastating it was 
to the family. My daughter was still in her medical residency and had a 
5-month old baby. My daughter died in 1996 at the age of 42 of 
metastatic breast cancer. That is much too young to die. I was even 
more deeply committed to the prevention trial after her death. It is so 
important that we do something to prevent this from happening to our 
young women. I still have one daughter and one granddaughter about whom 
I am very concerned. From the beginning of the trial, I felt that I 
wanted to be a part of a program that was dedicated to prevention of 
this terrible disease. If some way can be found to prevent this 
disease, I want to be part of it.
                                 ______
                                 
                  Biographical Sketch of Helene Wilson
    As a registered nurse who has elected to continue my career 
managing clinical trials for a major pharmaceutical company, I have 
taken my involvement in drug development and disease management and 
prevention to the personal level by participating in the BCPT. My 
daughter and I were interviewed for the Philadelphia Inquirer and I was 
involved in a television commercial for the Fox Chase Cancer Network.
    I have an Associates Degree in Applied Sciences in Nursing from 
Montgomery County Community College. When my children were old enough 
to be in school, I went back to college part-time and received my B.S. 
in Nursing from Gywnedd Mercy College. Because of my family history for 
breast cancer--my maternal grandmother, aunt, mother, and my fraternal 
aunt have all died of breast cancer--I have developed a strong interest 
in oncology that was manifested throughout my nursing career. I was the 
nurse manager of the original oncology unit at a local hospital. In my 
current position, I am responsible for the management of several large 
drug development trials.
    I am a divorced mother of two children, Bernadette and Joel, and am 
very interested in community and Church activities. I serve as a member 
of the Mt. Zion A.M.E. Church Chancel Choir, Community Health Education 
Committee, and the after school tutorial program, as well as volunteer 
for the American Cancer Society. I enjoy reading, needlepoint, sewing, 
traveling, and, most recently, scuba diving.
    When I first became a participant in this study and a member of the 
Participant Advisory Board, I hoped to increase women's awareness of 
issues relating to breast cancer and the importance of early diagnosis 
and treatment, especially in the African-American community. Over the 
last five years, I have become even more committed to those causes. I 
have lost a close friend and mother of my two young Goddaughters to 
breast cancer and have heard of numerous other women who have received 
a diagnosis of breast cancer. I know first-hand how breast cancer 
affects the family, and I believe that identification of a means to 
prevent the development of breast cancer is very important. I believe 
that the results of this trial will be beneficial, not only to me, my 
daughter, my new granddaughter, and my Goddaughters, but to all women 
today and future generations to come. I am proud to have been a 
participant in this study.
                                 ______
                                 
                           What Is the NSABP?
    The National Surgical Adjuvant Breast and Bowel Project (NSABP) is 
a cooperative group that was formed in 1971 to conduct clinical trials 
in breast and colorectal cancer research. The members of this 
cooperative group had been involved in collaborative research as early 
as 1958. The cooperative group now comprises the membership of the 
NSABP Foundation, Inc. headquartered in Pittsburgh, Pennsylvania.
    Current membership includes nearly 300 medical centers in the 
United States, Canada and Australia. Over 6,000 physicians, nurses, and 
other medical professionals in the NSABP member institutions and their 
satellites conduct NSABP treatment and prevention trials. Members as a 
group represent a wide range of institutional types: major medical 
centers, university hospitals, large oncology practice groups, and 
health maintenance organizations. The majority are non-university 
centers which can make state-of-the-art clinical trials available to 
patients near their homes. Each member institution has, at a minimum, a 
designated principal investigator who is responsible for overall 
conduct of the study at his or her site, and a program coordinator who 
is designated as the primary contact for all NSABP-related 
administrative and logistical matters.
    Institutional members conduct NSABP clinical trials including 
enrollment, protocol treatment, and submission of data for subjects and 
participants. Both the geographic accessibility to NSABP trials and the 
NSABP's track record of conducting clinically relevant, important, 
well-designed studies have contributed substantially to its success. In 
1997, NSABP treatment trial members enrolled more than 3,000 breast and 
colorectal cancer patients in 7 treatment trials. During the height of 
recruitment to the Breast Cancer Prevention Trial, more than 9,000 
participants were enrolled during a 12-month period.
    The National Cancer Institute is the primary source of funding for 
NSABP Member institutions to conduct NSABP clinical trials. NCI funding 
also supports two headquarters components of the NSABP: the NSABP 
Operations Center at Allegheny University of the Health Sciences, 
Allegheny Campus; and the NSABP Biostatistical Center at the University 
of Pittsburgh. The Foundation also receives support from other sources 
for ancillary studies, training and educational programs.
    Since 1958, the NSABP has played a vital role in improving the 
treatment of women with breast cancer. More recently, it has made 
contributions in the management of colon and rectal cancers. During 
this 40-year period, over 50,000 women and men were enrolled in NSABP 
clinical trials.
    Results from NSABP clinical trials have been a major factor in 
altering breast cancer management. The most obvious change in the 
treatment of the disease has been the reduction in the extent of the 
operative procedures. NSABP trials were the first to demonstrate that 
the radical mastectomy was no more effective than less extensive 
procedures. After 10 years of follow-up, an NSABP study shows that 
patients treated by lumpectomy (a breast-conserving procedure) followed 
by breast irradiation have a survival prognosis similar to those 
treated by mastectomy. Due in large part to these findings, a National 
Institutes of Health consensus conference recommended that lumpectomy 
and breast irradiation be the procedure of choice for women with 
primary breast cancer.
    The NSABP trials were among the first to evaluate the worth of 
systemic adjuvant chemotherapy for the treatment of breast cancer. 
Subsequent studies have evaluated hormonal therapies as well. Results 
from these trials indicated that such therapies reduce the recurrence 
rate of breast cancer and improve survival.
    The NSABP is conducting studies to evaluate the use of preoperative 
therapy in the treatment of breast cancer. The aim of these trials is 
not only to improve survival rates but also to reduce or eliminate the 
need for breast cancer surgery. In addition, the NSABP is evaluating 
therapies for noninvasive breast cancer and has enrolled 13,388 women 
in a Breast Cancer Prevention Trial to determine the effectiveness of 
tamoxifen in preventing the occurrence of breast cancer in women at 
high risk for the disease.
    Thus as the NSABP enters its fortieth year, it can look back on a 
proud history of changing the way breast cancer is treated * * * and 
now, potentially, prevented. This cooperative group has established a 
long history of successfully conducting large-scale, randomized 
clinical trials for the treatment and, most recently, for the 
prevention of breast cancer. The group already has in place the 
supporting components including an NSABP Operations Center, an NSABP 
Biostatistical Center, and a dispersed membership necessary to conduct 
large clinical trials and related studies. Each of these components are 
necessary but the most important, and the one unique to this 
cooperative group, is a membership with demonstrated capabilities and 
commitment to complete the research studies undertaken.

BCPT participant distribution

The United States:
    Alaska........................................................     1
    Alabama.......................................................   169
    Arkansas......................................................    13
    Arizona.......................................................   159
    California....................................................   840
    Colorado......................................................   128
    Connecticut...................................................    96
    District of Columbia..........................................    30
    Delaware......................................................    55
    Florida.......................................................   385
    Georgia.......................................................   174
    Hawaii........................................................   112
    Iowa..........................................................   289
    Idaho.........................................................     4
    Illinois......................................................   764
    Indiana.......................................................   216
    Kansas........................................................   215
    Kentucky......................................................   253
    Louisiana.....................................................   102
    Massachusetts.................................................   310
    Maryland......................................................   112
    Maine.........................................................    43
    Michigan......................................................   520
    Minnesota.....................................................   340
    Missouri......................................................   377
    Mississippi...................................................    40
    Montana.......................................................    96
    North Carolina................................................   412
    North Dakota..................................................    60
    Nebraska......................................................    84
    New Hampshire.................................................    86
    New Jersey....................................................   191
    New Mexico....................................................    37
    Nevada........................................................    48
    New York......................................................   601
    Ohio..........................................................   663
    Oklahoma......................................................   170
    Oregon........................................................   108
    Pennsylvania..................................................   786
    Rhode Island..................................................    36
    South Carolina................................................   172
    South Dakota..................................................    31
    Tennessee.....................................................   122
    Texas......................................................... 1,037
    Utah..........................................................    44
    Virginia......................................................   175
    Vermont.......................................................   188
    Washington....................................................   329
    Wisconsin.....................................................   295
    West Virginia.................................................    90
    Wyoming.......................................................     7
Canadian Provinces:
    Alberta.......................................................   330
    British Columbia..............................................   138
    Manitoba......................................................   134
    Ontario.......................................................   242
    Quebec........................................................   878
    Saskatchewan..................................................    40
Other locations:
    Bahamas.......................................................     1
    Mexico........................................................     2
    Puerto Rico...................................................     7
    Virgin Islands................................................     1
                                 ______
                                 
                              Attachment B
                  sample letter for bcpt participants
    Dear (participant's name): This letter contains important 
information about the NSABP Breast Cancer Prevention Trial (BCPT); the 
initial study results are going to be released! As a participant in the 
trial, you have made a major contribution to this research project and 
these findings would not be possible without the involvement of you and 
the other 13,000+ women in this trial.
    The important findings will be shared with the general public at a 
national press conference being held on Wednesday, April 8 in 
Washington, DC. Members from the BCPT Participant Advisory Board (an 
NSABP advisory board comprised of 16 women who are participating in the 
BCPT) will attend the press conference, along with the study organizers 
and officials from the National Cancer Institute. Until the public 
announcement occurs, we would appreciate all participants honoring our 
request for keeping this information confidential; please do not share 
it with other individuals until after April 8.
    On March 24, 1998, the Endpoint Review, Safety Monitoring and 
Advisory Committee (ERSMAC) responsible for monitoring the trial, held 
a regularly scheduled meeting to review the data to date from the 
study. The ERSMAC, formed before the start of the BCPT, is comprised of 
individuals with different areas of expertise such as medical oncology, 
biostatistics, and ethics. They are not affiliated with the NSABP and, 
thus, can provide a non-biased review of the trial. The ERSMAC meets 
every 6 months to review data on the study and to ensure the safety of 
the participants in the trial.
    After each meeting, the committee provides a recommendation about 
the study. Based on the most recent analysis of the data, this is now 
the first study in the world to show that a drug can reduce the 
incidence of breast cancer. Specifically, the study has shown that 
tamoxifen is effective in reducing the rate of breast cancer by an 
estimated 45 percent for the study population of women at increased 
risk for developing breast cancer. For example, this means that in a 
group of women similar to the BCPT population, rather than 100 breast 
cancers developing in the first 3\1/2\ years after taking tamoxifen, 
there would be 55 cases of breast cancer.
    The researchers are still analyzing all of the data to further 
understand the other potential benefits and the potential risks of 
taking tamoxifen to prevent breast cancer, and to determine if the drug 
works better in some groups of women than others. For example, 
tamoxifen use has historically been associated with an increased risk 
of developing endometrial cancer in women who have not had a 
hysterectomy (surgical removal of the womb). It has also been 
associated with an increased risk of deep vein thrombosis (blood clots 
in large vein, which could potentially travel to the lungs), and 
pulmonary embolism (a blood clot that has traveled to the lungs). The 
overall BCPT data indicate that these are still possible risks; 
however, the data show that the rate of these risks does not exceed 
what has been originally predicted for the study. As more information 
about the specific benefits and risks becomes known, you will be 
informed.
    The medical recommendations that will be available from this data 
are still being developed and will be made available to your BCPT 
doctor. In general:
  --If you have been on tamoxifen for less than 5 years and have not 
        had problems, you may consider continuing tamoxifen therapy 
        until you take the drug for 5 years.
  --If you were on tamoxifen for all 5 years, there is currently no 
        evidence indicating that additional tamoxifen therapy beyond 5 
        years is beneficial.
  --If you have been on a placebo, you may consider starting tamoxifen 
        therapy after consulting with your doctor. You may also be 
        eligible for a new study being planned that will compare 
        tamoxifen to another drug for the prevention of breast cancer 
        in post-menopausal women. This study is planned to begin in 
        Fall 1998.
  --If you are among the group of women who have developed breast 
        cancer during the BCPT, your treatment plans have already been 
        determined. Your contribution to helping others at risk for 
        breast cancer cannot be overstated.
    The availability of these findings does not mean that ``the study 
is over.'' The only difference in the trial is that participants will 
know what therapy they were taking. The follow-up examinations that are 
required in this trial represent good health care for women at 
increased risk for developing breast cancer. It is important that 
participants continue to receive this follow-up care, either at their 
BCPT center or through their own health care provider. Regardless of 
who performs your follow-up examinations, the NSABP is still interested 
in receiving data about your health status. This additional data will 
answer more questions about tamoxifen's effectiveness in reducing the 
incidence of breast cancer. Presently, the NSABP would like to collect 
information about your follow-up for at least the next 2 years.
    Although this letter may seem impersonal, it was the most effective 
way to get information to you and your 13,000+ partners in this 
research study before it is shared with other researchers, the medical 
community, and the general public. We and the NSABP made a commitment 
that every effort would be made to share the study results with the 
trial participants as soon as possible after they became available. In 
the next week or so, it is likely that you will hear the results 
described and discussed on television and in the newspapers. The NSABP 
has promised to provide us with updated study information as it becomes 
available. We will continue to keep you informed.
    You can be very proud that you have been an important part of this 
project and we thank you for your contribution.
            Sincerely,
                        Appropriate BCPT physician and coordinator.
                                 ______
                                 
 Instructions for Unmasking of Therapy Assignment for BCPT Participants
    As part of this mailing you will find a listing which provides the 
umnasked therapy assignment for all participants attributable to your 
BCPT subcenter (i.e., according to records at the NSABP Biostatistical 
Center these participants have been followed on protocol by staff at 
your subcenter). The listing is sorted alphabetically by the 
participant's last name (with ``consent withdrawals'' grouped at the 
end of the list).
                   notification to bcpt participants
    The method by which you elect to provide this information to 
participants is at your discretion. However, every effort should be 
made to notify the participants prior to the national press conference 
scheduled for April 8, 1998. In your communication to the participants, 
the information that is provided in the enclosed sample letter should 
be conveyed to each participant.
    If you decide to notify your participants by mail, the enclosed 
sample letter may be provided to them after it is personalized for your 
BCPT site. If you decide to notify your participants by mail, the NSABP 
has provided (enclosed in this mailing) participant-specific 
notifications which identify the therapy to which each participant was 
assigned; your use of these participant-specific notifications is 
optional. These participant-specific sheets have been provided for all 
participants followed by your site except those who are consent 
withdrawals, lost to follow-up, or who are deceased. [While 
participants or their survivors in those categories should be notified, 
it is unlikely that the information will be relayed by mail.] These 
participant-specific sheets are sorted alphabetically by the 
participant's last name.
    If you decide to notify participants by telephone, please be 
certain to emphasize the following important points:
  --Without their contribution to this study through their enrollment, 
        these results would not be available in such a timely fashion.
  --It is important that they continue to receive follow-up 
        examinations and follow-up care.
  --More information about the impact of these results on their future 
        course of therapy will be forthcoming in the near future.
  --Their decision about whether to begin or continue tamoxifen therapy 
        should be made in consultation with their BCPT physician.
    With either method of notification, be sure to include 
documentation in the participant's study record when they were 
notified, by whom, and by what method (mail, phone, personal visit).
             notification to the institutional review board
    Please convey a copy of the Sample Letter to Participants and the 
March 31, 1998 Confidential Memorandum Regarding Initial BCPT Results 
to your IRB Chairperson as soon as possible. The NSABP has consulted 
OPRR, and OPRR concurs that the information to participants should be 
conveyed as quickly as possible in order to eliminate the immediate 
hazards associated with participants receiving incorrect, incomplete, 
or distressing information through the media. If possible, please speak 
with your IRB Chairperson personally about this and stress the 
importance of maintaining confidentiality until April 8, 1998. This IRB 
notification should not delay the immediate dissemination of the 
information to your participants.
    We realize that our request for this information to be disseminated 
before the press conference may be difficult to meet, however, we feel 
it is important that every participant be made aware of the upcoming 
results, and that they hear about this information from the 
investigators whom they have become familiar with over the course of 
their participation.
                                 ______
                                 
                              Attachment C
                  Statement of President Bill Clinton
                     breast cancer prevention trial
    Today's new research findings about the potential use of the drug 
tamoxifen to prevent breast cancer are an historic step in the ongoing 
fight against this deadly disease. Breast cancer strikes one in eight 
American women, and about 180,000 women in the United States will be 
diagnosed with breast cancer in 1998. Each of us has a sister, a 
daughter, a friend, or in my case, a mother, who has fought against it.
    The landmark Breast Cancer Prevention Trial gives us new hope that 
some women at high risk for breast cancer may actually be able to 
reduce their risk of getting this life threatening disease. It is an 
important contribution to our national battle to detect, prevent, treat 
and finally cure breast cancer for generations of women to come.
                                 ______
                                 
 Statement of Donna E. Shalala, Secretary of HHS on the Breast Cancer 
                            Prevention Trial
    Despite all of our efforts to detect, prevent and treat breast 
cancer over the last few years, women have had no proven means to 
reduce their risk of getting this deadly disease. Instead we have 
relied on frequent check ups and mammograms to detect breast cancer at 
an early stage. Today's new research findings are an historic step 
toward more effective prevention of breast cancer.
    This stunning result does not come without its limitations, 
however, and those who will choose to consider tamoxifen should consult 
with their doctors in order to weigh the risks and benefits for 
themselves.
    The Food and Drug Administration is committed to a priority review 
of this new use of tamoxifen. And the National Cancer Institute will 
develop tools for women and their physicians to help them in weighing 
the risks and benefits.
    While the results of the Breast Cancer Prevention trial may not 
have an immediate impact on all women, the study designers have given 
women more options to deal with the risk of breast cancer. Continued 
participation by women in trials like this will greatly aid researchers 
in developing newer and better methods of fighting breast cancer as 
well as other types of cancer.
    We must also remember that high-quality mammography is the most 
effective technology currently available to detect breast tumors. 
Regular mammography screening starting at age 40 can decrease the 
chance of dying from breast cancer. In addition, early detection may 
prevent the necessity of removing lymph nodes and in some cases may 
prevent the need for removing the entire breast. This is especially 
important for older women, for whom Medicare coverage of annual 
mammograms is so important.
                                 ______
                                 
Statement From FDA Lead Deputy Commissioner Michael A. Friedman, M.D., 
            on the NCI Breast Cancer Prevention Trial Study
    The Food and Drug Administration applauds research efforts 
conducted on important issues like breast cancer prevention. For the 
tens of thousands of women who are diagnosed with breast cancer each 
year, this landmark study is encouraging news.
    While initial reports about the potential utility of tamoxifen in 
preventing breast cancer are certainly positive, like all drugs, there 
are also some risks. Although tamoxifen has been approved for the 
treatment of breast cancer patients, FDA must first review the clinical 
trial data before approving it for the prevention of breast cancer. We 
are already in contact with the NCI and the study sponsors to obtain 
the data. Once we receive it, we are committed to a thorough review 
within six months.
    The federal government has been dedicated to investing time and 
resources into breast cancer research. This study is another example of 
the importance of continued research in our fight against this life 
threatening disease.
                                 ______
                                 
  Zeneca Commends the NCI/NSABP in Light of Breast Cancer Prevention 
                             Trial Results
    Zeneca commends the National Cancer Institute (NCI) and National 
Surgical Adjuvant Breast & Bowel Project (NSABP) for their leadership 
in conducting the Breast Cancer Prevention Trial which showed that 
women at increased risk of developing breast cancer who took tamoxifen 
(also known as the brand name Nolvadex (tamoxifen citrate) were 45 
percent less likely to develop breast cancer than women who received 
placebo. ``The news that tamoxifen is shown to provide significant 
preventive benefits in women who are at increased risk of developing 
breast cancer is a long-awaited development in the fight against breast 
cancer. The women who participated in this trial are to be applauded 
for their role in this historic study,'' says Gerard T. Kennealey M.D., 
Vice President of Medical Affairs, Zeneca Pharmaceuticals. ``Zeneca is 
prepared to work closely with the NCI, NSABP, and the Food and Drug 
Administration to determine the appropriate next steps.'' This trial is 
the largest of three prevention trials being conducted worldwide. In 
each trial, Zeneca provided free of charge both the active drug, 
Nolvadex, and the matched placebo, as well as regular information 
updates from our extensive data base which reflects about 10 million 
patient-years of experience. Zeneca has committed to provide Nolvadex 
to study participants for up to five years. We will continue to provide 
the product to women (through the NCI/NSABP) in the Nolvadex arm for 
the balance of the five-year duration of the study and to provide the 
drug to women in the placebo arm should they and their physician choose 
this option. Nolvadex is among the world's most studied cancer 
medications with clinical data accumulated for more than 25 years. The 
efficacy and safety profile of Nolvadex reflects more than 10 million 
patient-years of experience in 110 countries. Zeneca Pharmaceuticals is 
a business unit of Zeneca Inc., a $3.4 billion bioscience business with 
approximately 7,200 employees in the United States. Zeneca Inc. is a 
wholly-owned subsidiary of the U.K.-based Zeneca Group PLC (NYSE:ZEN), 
a major $8.6 billion international bioscience business engaged in the 
research, development, manufacturing, and marketing of ethical 
(prescription) pharmaceuticals, agricultural and specialty chemical 
products, and the supply of health care services.
                                 ______
                                 
 Tamoxifen Breast Cancer Prevention Trials, Pennsylvania Breast Cancer 
                     Coalition, Board of Directors
    Pat Halpin-Murphy, President and Founder of the Pennsylvania Breast 
Cancer Coalition (PBCC), serves on the board of the National Surgical 
Adjuvant Breast and Bowel Project (NSABP) which is conducting the 
tamoxifen prevention trials nationally. Norman Wolmark, M.D., chairman 
of the NSABP, also serves on the board of the Pennsylvania Breast 
Cancer Coalition.
    Ms. Halpin-Murphy is a breast cancer survivor who founded the PBCC 
in order to educate the public about the need for research, education 
and outreach. Pennsylvania First Lady Michele Ridge serves as honorary 
chairperson of the PBCC.
    ``Results from the tamoxifen prevention trials are very 
encouraging,'' says Ms. Halpin-Murphy, ``because, for the first time, a 
clinical trial has shown that under certain circumstances, the use of a 
drug can help prevent breast cancer. The women who participated in the 
trials were considered at high-risk for breast cancer because of a 
family history of the disease. This is the breakthrough we have been 
waiting for.''

                            clinical trials

    Senator Specter. Before we move on to Ms. Pearson, what 
suggestion would you have here? You have identified yourself as 
being African-American and have said that women of color do not 
participate in these clinical trials. What suggestion would you 
have, if any, as to how to encourage other African-Americans to 
be participants?
    Ms. Wilson. My suggestion would be to get more people 
involved at the grassroots, to actually go into the community 
and to encourage them on a 1-to-1 basis.
    I hope that women, the minority women who were in this 
study, will have the opportunity to go out and encourage other 
women to do what they had done, to set an example and just to 
encourage others to repeat what we have done.
    Senator Specter. Thank you very much, Ms. Wilson.

                  SUMMARY STATEMENT OF CYNTHIA PEARSON

    I would like to turn to Ms. Cynthia Pearson, executive 
director of the National Women's Health Network. She has long 
been involved in women's health issues, served as executive 
director of a community based women's health clinic, is on the 
board of directors of the National Breast Cancer Coalition and 
the Steering Committee of the National Action Plan on Breast 
Cancer.
    Ms. Pearson is a graduate of the University of California 
at San Diego.
    Welcome, Ms. Pearson. We look forward to your testimony.
    Ms. Pearson. Thank you, Mr. Chairman. I appreciate the 
opportunity to testify today.
    I think I have been invited to come today to provide a note 
of balance in some respects and also caution.
    First, it is clear that we do not yet know what the long-
term risks and benefits of tamoxifen are, nor do we know 
whether the short-term benefits, which were recently announced 
and are summarized on the posters over here are likely to make 
a difference in the lives of most women who would eventually 
develop breast cancer.
    Although these results show clearly that tamoxifen can 
prevent breast cancer for a few years, at least, in women at 
high risk, they also show very clearly that tamoxifen causes 
serious complications.
    But what they do not show, although scientists have made 
these data available publicly, but what we believe is not 
getting enough attention, is that, even within this trial of 
high risk women, there were a group of women for whom the risks 
outweighed the benefits or at least were just a wash-out. Those 
are the women who Dr. Klausner described as being over 50 when 
they started the trial and having a uterus.
    Senator Specter. That was over 50 and what?
    Ms. Pearson. And also having a uterus, so that they could 
be at risk for the development of uterine cancer.
    In every thousand women in that category, for every 20 
breast cancers that were prevented, 22 life threatening 
complications were caused. You might have heard arguments that 
these other risks are not so bad. However, as has been said 
already, they can potentially be fatal. Some women, two women, 
did die of tamoxifen caused complications in the trial and 
probably the only reason why there were not more tamoxifen 
caused deaths is that this trial was done at the highest 
standard with extremely careful monitoring, far beyond what 
happens in the real world for most women.
    Now we hope as hard as anyone does that tamoxifen will be 
shown to have long-term benefits. But we need to acknowledge 
that we don't know that yet and there are at least two possible 
reasons why that might not turn out to be true.
    Now we do know that women who take tamoxifen for breast 
cancer treatment for 5 years have a long-lasting benefit that 
lasts after the 5 years. But we don't know yet whether that 
lasting effect after you stop taking the drug will be present 
in healthy women.
    We also know that tumors which occur in women previously 
treated with tamoxifen may be less treatable because tumors can 
become resistant to tamoxifen or even feed on it. This was 
shown in another NIH supported study in which breast cancer 
patients who took tamoxifen for more than 5 years were actually 
more likely to die of breast cancer than those who took 
tamoxifen for only 5 years.
    I have attached NIH's, NCI's own clinical announcement so 
that you can look for more details.
    Even recognizing, though, these significant risks, the 
possibility that many women will not benefit in the terms of 
trading one risk for another, and the unanswered questions, the 
National Women's Health Network strongly supports women's right 
to choose this drug if they are properly informed of the risks 
and benefits.
    We are concerned, though, that probably for the majority of 
women who will eventually develop breast cancer, given what we 
know now, the risks may well outweigh the benefits, and we are 
concerned that this information is not being communicated as 
clearly and forcefully as it needs to be.
    We know from experience that patients are often not well 
informed about risks and benefits by many physicians and that 
many physicians will casually overprescribe drugs to people who 
don't need them. There is the recent tragic misuse of the diet 
drug combination phen-fen and the brand new websites for the 
male impotence drug, where all you need is a click on a mouse 
and a credit card number and you can get your prescription. 
That is a tragic misuse waiting to happen.
    Given this, we have two recommendations. One: Women and 
doctors urgently need accurate, realistic information about 
tamoxifen that makes it clear that the known risks outweigh the 
short-term benefits potentially for relatively many women. It 
is true when Dr. Klausner says there are many women at very 
high risk. But relatively there are more women not at that high 
level of risk, and even though you have heard very balanced 
statements today, we believe that NCI's first descriptions of 
the trial results as remarkable with no qualifying words in 
those first sentences means that NCI and NIH need a little bit 
of help from the outside, from public health and prevention 
experts, from consumer advocates in developing and getting the 
final format of the educational materials about risks and about 
tamoxifen worked out. We recommend that you encourage that 
process.
    Finally, to wrap up, I would just like to say that our 
second recommendation is that NCI should immediately commit 
itself to life-time followup for all the women that were so 
committed to the cause that they participated in this trial, 
and immediately stop recruiting women who were on the placebo 
group in this trial to the new trial being proposed for 
tamoxifen versus raloxifene. Preventing breast cancer is good 
in and of itself, but saving lives by the use of tamoxifen is 
better.
    If tamoxifen only delays breast cancer, instead of 
preventing it, or if it creates a more deadly strain of breast 
cancer resistant to treatment, it won't save lives. The only 
way to know is to continue the followup of Ms. Wilson and all 
the women who participated in the trial for many more years, 
not the 2 years that were in the original protocol.
    This will require additional funding which we 
wholeheartedly support and encourage Congress, with your 
leadership, to provide.

                           PREPARED STATEMENT

    It will also mean that this group of women should not be 
actively encouraged, although, of course, they have the right 
to do so. But they should not be actively encouraged to 
participate in studies of hormone drugs which would then make 
it difficult to tell.
    [The statement follows:]

                 Prepared Statement of Cynthia Pearson

    Mr. Chairman and Members of the Subcommittee, thank you for the 
opportunity to testify today. I am Cynthia Pearson, Executive Director 
of the National Women's Health Network. the only national public 
interest membership organization in the United States that is devoted 
solely to the health of all women. Unlike many other health advocacy 
organizations. we do not receive any financial support from the Federal 
government, pharmaceutical companies, trial lawyers, or any other 
organization with a financial interest in the provision of health care 
services.
    I am here today to urge caution about the use of tamoxifen to 
prevent breast cancer. The study you are hearing about today was 
stopped early, so we do not yet know what the long-term benefits or 
risks are. Even the short-term benefits shown in this study are 
unlikely to make a difference in the lives of most women. Although the 
results of the Breast Cancer Prevention Trial indicate that tamoxifen 
can prevent breast cancer for a few years in women at high risk, the 
study also indicates that tamoxifen causes very serious. even fatal, 
complications. The risks of tamoxifen may outweigh the benefits for 
most women at risk of breast cancer.
    Let me be specific: For every 1,000 women (with a uterus) over the 
age of 50, 20 breast cancers were presented and 22 potentially life-
threatening complications occurred. Of the 20 breast cancers prevented. 
17 would have been invasive and 3 would have been non-invasive. Of the 
22 life-threatening complications. 10 were blood clots and strokes and 
12 were uterine cancers. You may have heard arguments that these risks, 
especially, uterine cancer, are somehow ``not so bad.'' However, 
uterine cancers can be fatal, and the reason why the uterine cancers in 
this study were caught early is because women were monitored much more 
carefully than they would have been in the real world.
    We hope that tamoxifen will have long-term benefits, but we're not 
sure. Breast cancer patients who take tamoxifen for 5 years have a 
long-term benefit, but we don't know if it will have the same long-
lasting effects for healthy women who have never had breast cancer. 
Women need to know if this drug can truly prevent, and not delay, 
breast cancer. Also, tumors which occur in women previously treated 
with tamoxifen may be less treatable. Apparently, tumors can become 
resistant to tamoxifen, or even learn to feed on the drug.
    A previous NIH study shows that breast cancer patients who took 
tamoxifen for more than 5 years were more likely to die of breast 
cancer than those who took tamoxifen for only 5 years. In fact, that 
study was stopped early because of the clear danger of long-term 
tamoxifen use. NCI had originally planned to compare 10 years of 
tamoxifen with 5 years of use, but determined that it would be 
unethical to do so because of these deaths. I have attached to my 
testimony NCI's own announcement, which showed that 9 years after 
beginning treatment. 92 percent of the women who took tamoxifen for 
only 5 years were alive and free of disease, compared to 86 percent of 
the women who took the drug continuously for the entire 9 years.
    What about those woman who take tamoxifen to prevent breast cancer 
and who later get breast cancer anyway? Will they be resistant to 
tamoxifen and therefore unable to use it to treat their breast cancer? 
That would be potentially disastrous because tamoxifen is normally such 
an effective treatment for breast cancer.
    And let's remember that there are other potential problems, 
Including quality or life issues that will prevent many women from 
choosing it. It can't be taken by women who want to become pregnant, 
and in fact, causes side effects similar to menopause.
    We support women's right to choose this drug if they are properly 
informed of the risks and benefits. We believe that the benefits may 
well outweigh the risks for women with an extremely high risk of breast 
cancer, such as women with the breast cancer gene or women who have had 
a diagnosis of non-invasive cancer. These women potentially have a 30 
percent risk of developing, breast cancer within the next 20 years. 
However, most women who develop breast cancer are not in this ultra-
high-risk population--most, in fact, have no known risk factors. In the 
general population, risks will outweigh benefits. We are also very 
concerned that age alone not be considered sufficient risk to justify 
using tamoxifen for prevention, especially because the risks of 
tamoxifen are higher for older women. Unfortunately, we know from 
experience that patients are often not well informed of the actual 
risks and benefits. For example, the recent tragic misuse of the diet 
drug combination phen-fen shows that doctors will prescribe drugs to 
hundreds of thousands of patients who are not likely to benefit. One of 
our major concerns is that the recent hype regarding, this study will 
result in millions of women taking tamoxifen with little likelihood of 
short-term benefit and before we even know what the long-term benefits 
are and that the long-term risks are.
    We have the following recommendations.
  --Women and their doctors urgently need accurate, realistic 
        information about tamoxifen which makes it clear that the known 
        risks outweigh the short-term benefits for most women. Given 
        NCI's inappropriate public announcement of the results as 
        ``remarkable'' and a ``breakthrough'', we cannot count on the 
        NIH for unbiased information. We recommend that Congress advise 
        the NIH to create a process which involves public health 
        experts and consumer advocates in the development and final 
        format of educational materials about tamoxifen.
  --NCI should immediately commit itself to life-time follow-up for all 
        women who participated in the Breast Cancer Prevention Trial. 
        NCI should also immediately stop its unethical recruitment of 
        women in the placebo group to their new trial comparing 
        tamoxifen to raloxifene. While preventing breast cancer is 
        good. what is really important is determining, whether 
        tamoxifen actually saves lives. If it only delays breast cancer 
        instead of truly preventing it. or if it creates a more deadly 
        strain of breast cancer resistant to treatment, it won't save 
        lives. The only way to know whether or not tamoxifen saves 
        lives is to continue the follow-up of women participating in 
        the trial for many more years. This will require additional 
        funding, which we wholeheartedly support and encourage Congress 
        to provide. It will also mean that this Group of women should 
        not be asked to participate in other studies of hormone drugs. 
        Currently, NCI is actively encouraging women who were given 
        placebo pills to take part in a study of tamoxifen compared to 
        raloxifene. Obviously, this destroys any possibility of finding 
        out whether or not tamoxifen saves lives. This is outrageous.
    The nation has invested 50 million dollars in the Breast Cancer 
Prevention Trial. While the results clearly indicate that tamoxifen 
offers a new and welcome option for a small group of women in dire 
need, it is a blip, not a breakthrough, in our shared efforts to 
eradicate breast cancer. We need to work together to ensure that women 
and their physicians are appropriately informed about the true 
implications of this study. And women deserve a commitment to finding 
out whether or not preventive tamoxifen saves lives.

                               tamoxifen

    Senator Specter. Ms. Pearson, there can be no disagreement 
about the maximum amount of information and lifetime followup 
certainly sounds desirable. Your cautionary words are obviously 
very important, I would like your opinion, your judgment, on 
this. If you have a woman under 50, who does not have a 
uterus--you had said if you were over 50 and if you had a 
uterus, there is a real risk potential, a high one. For someone 
who is a high risk cancer patient under 50, without a uterus, 
what would you suggest--that tamoxifen is good?
    Ms. Pearson. I would suggest looking very carefully about 
what that high risk is. You are very educated about cancer. You 
use that term carefully.
    Many people in the community, including many community 
doctors, use it casually to mean someone who maybe gave birth 
to their first child in their late thirties.
    Senator Specter. Well, if you have a high risk of breast 
cancer and I am about to ask Dr. Wolmark to define high risk, 
then what?
    Ms. Pearson. If a woman has been diagnosed with 
precancerous conditions through the biopsy, if a woman has an 
extremely strong family history, the discussion about tamoxifen 
between her and her doctor is absolutely a good idea and we are 
glad that there is this new option.
    Senator Specter. OK. But beyond the discussion, if you have 
the high risk characteristics, if you are under 50, if you do 
not have a uterus, then do you think that it is wise to 
prescribe and take----
    Ms. Pearson. It is a reasonable choice----
    Senator Specter. Let me finish the question. Do you think 
it is wise to prescribe and take tamoxifen?
    Ms. Pearson. It is a reasonable choice for a woman to make 
in that situation.
    Senator Specter. Would you define high risk for us, Dr. 
Wolmark, so that we have that on the record?
    Dr. Wolmark. I think that is not a straight-forward 
formula, which I think makes the issue a little bit more 
complex.
    Senator Specter. Dr. Wolmark, there are a lot of doctors 
listening to C-SPAN and a lot of doctors following you. It may 
not be easy, but this is a unique opportunity to convey a lot 
of information as best you can as to what high risk means.
    Dr. Wolmark. Well, the original study was formulated on the 
premise that the women who would enter into this study would 
have the risk equivalent to a 60-year-old patient or 
participant. That implied that over the next 5 years, her 
likelihood of developing breast cancer was 1.7 percent.
    So those women who are under 60 years of age must have a 
risk equivalent to that to have been eligible for this study.
    Also, there are many combinations of risk factors that 
would make a woman eligible for this study or equivalent to a 
risk of 60 years of age or greater. And for those who are 
listening on C-SPAN, if you had a 35-year-old woman, if she had 
two first degree relatives plus a history of a personal breast 
biopsy, she would qualify. But the criterion that made her of a 
risk equivalent to a 60-year-old woman is not necessarily the 
same and is not the same for a woman who is age 40. In that 
category, for example----
    Senator Specter. Dr. Wolmark, let me interrupt you. You can 
transmit that to the doctors. Maybe they will understand it.
    Is there anything you can say that would give some general 
parameters to a woman who worries as to whether she is high 
risk and what that means to her?
    Dr. Wolmark. Well, as she approaches age 60, she requires 
fewer factors and fewer discriminants to qualify for that high 
risk. If she is younger, then she will require more factors.

                      DEFINING HIGH RISK CATEGORY

    Senator Specter. Dr. Klausner, let me ask you. We don't 
have a whole lot of time. They are going to start a series of 
votes, three votes, in just a few minutes and I am going to 
have to face a choice as to how far we have gone as to whether 
we come back and keep you waiting. These are very important 
questions.
    Would you try your hand at defining a high risk category?
    Dr. Klausner. For women who are concerned they are at high 
risk, the two most important issues are their family history 
and family history specifically in close relatives--first 
degree relatives are mothers, sisters, daughters--and whether 
they personally have a history of breast disease--an abnormal 
biopsy, for example, or a precancerous lesion. Those are the 
two highest risk considerations.
    There are other factors, but they have to be calculated, we 
believe, with their physician. So would be the two issues that 
women could know themselves. But they have to check it out. We 
have done studies.
    Senator Specter. Obviously, they have to go to a doctor and 
have a fuller explanation than you can give them here on a 
sound byte.
    Dr. Klausner. Yes, right. That is exactly right, sir.

                       APPROVAL OF TAMOXIFEN USE

    Senator Specter. Let me move to a number of other subjects 
because, as I say, our time is limited. Let's explore this a 
little more fully. I did not want to take the time out before 
we had finished giving everybody a chance to testify. On 
tamoxifen, it is currently approved by the FDA for secondary 
breast cancer treatment, that is, following a mastectomy or 
radiation therapy. It is also used for metastatic disease.
    Let me follow up with you, Dr. Varmus, because we had 
started to discuss it. If a doctor wishes to use it for breast 
cancer prevention, which the doctor may do. However, the 
company which makes it, Zeneca, cannot advertise or market 
tamoxifen as a preventive. Is that a summary statement of it?
    Dr. Varmus. That is correct at the present time.
    Senator Specter. Moving into somebody else's field, why 
does it take the FDA 6 months to make a determination on 
tamoxifen so that there can be more information in the field 
and there can be advertisements for it and more information to 
women as a preventive?
    Dr. Varmus. Senator Specter, the statement that was made by 
Dr. Friedman was that within 6 months this would happen.
    What has to occur is that the paperwork for submission to 
FDA needs to be prepared after the study is carefully reviewed. 
Zeneca then would submit the application for this additional 
indication. Experts would then be assembled to review the data.
    That will be done, I would say, in somewhere between 3 and 
6 months, and I think Dr. Friedman was cautiously giving an 
outside boundary.
    Senator Specter. The question which arises here in the 
Congress is whether it could be done faster.
    We recently had changes in the Food and Drug Administration 
law. In Ms. Wilson's testimony, she expresses her feelings of 
being a walking time bomb for cancer and that she really 
welcomed the opportunity to be in this test group. I think 
there are many women who would like to have the availability of 
tamoxifen.
    Dr. Varmus. It is available.
    Senator Specter. Yes; they can get it now because a doctor 
can prescribe it since it is OK for some collateral use. But 
there are many women out there who do not know about it and 
will not know about it in the absence of advertising or a real 
promotion of tamoxifen.
    Dr. Varmus. We are trying to provide a great deal of 
information. We believe that a very, very large segment of the 
physician population and the patient population will be aware 
of these new findings as a result of this hearing.
    Senator Specter. I think you have done a good job with that 
and I will reserve that question for the FDA.
    Dr. Varmus. I think that will be wise.
    Senator Specter. We will contact them and we will ask them 
why not sooner, what is the soonest they can do this?
    Dr. Varmus. Right now, they are waiting for the 
application.
    Senator Specter. Dr. Wolmark, did you have a point you 
wanted to make?
    Dr. Wolmark. Senator, in all fairness, I have had 
discussions with Mike Friedman, who said that he would do 
whatever is necessary to expedite this as quickly as possible. 
I think that we can have it done sooner than 6 months.
    Senator Specter. Would you care to give an estimate as to 
how soon?
    Dr. Wolmark. Well, we would like it tomorrow----
    Senator Specter. That's good.
    Dr. Wolmark [continuing]. But I don't think it will be by 
then. [Laughter.]
    Senator Specter. We'll take it up with him and we will 
encourage him to do it as fast as he can.
    What more will be done on tamoxifen, Dr. Wolmark, with 
respect to the research and the study which your very 
distinguished group has undertaken?
    Dr. Wolmark. We think we need to refine some of the risk-
benefit models, as Dr. Klausner has said, and that is currently 
ongoing to provide the best information relative to the risk-
benefit to a particular woman who is at increased risk for the 
development of the disease.
    Having said that, ultimately the decision will be an 
individual one based on having accurate information of risk 
benefit.
    I think Ms. Pearson clearly underscored that example. She 
looked at the data relative to women over 50 and said that, in 
her conclusion, the risks were equivalent to the benefits.
    I think other people looking at that would conclude 
something very different and state that they would wish to 
avail themselves of tamoxifen seeing exactly the same data set.

                        RALOXIFENE AND TAMOXIFEN

    Senator Specter. With the limited time we have, let me move 
for a moment or two to raloxifene.
    Dr. Klausner, could you give a distinction between 
tamoxifen and raloxifene. We just heard of raloxifene in the 
media yesterday. What is the difference?
    Dr. Klausner. Raloxifene and tamoxifen are similar drugs 
and they act on estrogen receptors, either turning them on or 
turning them off in different tissues. Raloxifene recently has 
been approved by the FDA for use in postmenopausal women to 
prevent osteoporotic fractures.
    The recent reports in the news relate to analysis of the 
several studies looking at women that took raloxifene for 
prevention of osteoporotic fractures to see whether----
    Senator Specter. So raloxifene is for osteoporosis 
primarily.
    Dr. Klausner. That is what it has been approved for.
    Senator Specter. But testing has shown, according to the 
New York Times today that raloxifene does not appear to raise 
the risk of uterine cancer as a side effect contrasted with 
tamoxifen.
    Is that an accurate report?
    Dr. Klausner. That is what the New York Times says. We are 
concerned that those studies----
    Senator Specter. I'm not asking you if I have accurately 
quoted the New York Times. I'm asking you if the New York Times 
is correct.
    Dr. Klausner. We are not sure. That is why we think this 
has to be studied.
    In those studies, women were observed for only about 2 
years, 28 months, I think, total. Very few women were actually 
specifically looked at in terms of what was happening in their 
uterus. We are interested in terms of the possibility, and I 
think it is that. It is a possibility that raloxifene is 
similar to tamoxifen in some respects and may be different in 
having less of a stimulatory effect on the uterus. That is 
exactly why we want to do a clinical trial to compare them.
    We won't know the answer until we directly compare them. 
There has not been long enough experience to say that for sure. 
It is just a suggestion.
    Senator Specter. So your judgment is the clinical trials, 
which you conducted with tamoxifen, move you far ahead in that 
analysis and you have not had the clinical trials in raloxifene 
to give you the same kind of assurances.
    Dr. Klausner. That is exactly right.
    Senator Specter. Even though there may be some preliminary 
indicators that tamoxifen does not cause uterus cancer, you 
really don't know about that.
    Dr. Klausner. I think that's right.
    Senator Specter. So tamoxifen is the better of the two 
given the limitations which have already been described.
    Dr. Klausner. It's the only drug for which we have 
evidence, the best type of evidence, which is from a randomized 
clinical trial.
    Senator Specter. Dr. Klausner, in the past I have asked you 
how much you would like to have by way of funding for research. 
Let me try again.
    My sense is--and I have said this to you before and to Dr. 
Varmus--with a Federal budget of $1.7 trillion, we can take 
care of our priorities. I believe that it has been modestly 
stated to double NIH's funding over 5 years, which would be 
more than $2.5 million a year.
    We have seen what has gone to the National Cancer 
Institute. But if you had your druthers, what would the figure 
be?
    I'm about to ask Dr. Varmus the same question for the whole 
National Institutes of Health. So I give you just a little 
warning there.
    What is your figure, Dr. Klausner?
    Dr. Klausner. According to the law, I am asked what my 
druthers would be in the formal NCI bypass budget, and in that 
bypass budget we asked for a budget of $3.191 billion in order 
to attempt to do the many things we very much would like to do 
and cannot.
    Senator Specter. Dr. Varmus, what would the NIH budget be? 
First of all, this is a two-part question. What would you like 
the NIH budget to be? Second, what would the NIH budget have to 
be to give Dr. Klausner his druthers?
    Dr. Varmus. They are related questions, obviously, Senator 
Specter.
    The NIH, as you know, has requested an increase of about 
8.4 percent for this coming year. That is the President's 
budget request for the NIH. We believe that the NIH can do well 
with that.
    You requested a few weeks ago, before our appropriation 
hearing, that I ask all the Institute Directors what each would 
like to spend in an ideal world where there were not other 
constraints upon the budgetary process. The aggregate number, 
the average for the whole of NIH--was a 23-percent increase, 
which would bring us up to--I don't have the numbers with me--
something close to $17 billion for the coming year.
    Senator Specter. Well, we are going to take a close look at 
those figures as to fiscal year 1999 and future years. I do 
believe that the NIH is the crown jewel of the Federal 
Government, maybe the only jewel of the Federal Government. You 
have had such spectacular results on this breakthrough on 
tamoxifen.
    Dr. Wolmark, to what extent has the funding for the 
National Institutes of Health enabled these remarkable 
tamoxifen breakthroughs to have occurred?
    Dr. Wolmark. Without that funding, these trials clearly 
could not have been done. They take a significant amount of 
money to carry out and they take a significant amount of 
commitment from the participating members, the data managers, 
and the patients who do far more than what the budget pays them 
to do.
    We estimate that the budget provides only for two-thirds 
the actual costs in time and effort, and that does not take 
into account the medication which is provided free of charge by 
the companies.
    Senator Specter. Is your research budget adequate?
    Dr. Wolmark. Our research budget can always be greater and 
we would be able to bring more patients into these trials if 
our budget were larger.
    Senator Specter. How much more?
    Dr. Wolmark. Well, we would want a 40-percent increase.
    Senator Specter. If you brought more patients in for the 
clinical trials, do you think you would have better answers to 
some of the obviously unanswered questions?
    Dr. Wolmark. They would certainly be more rapid answers, 
and that would enable us to move on to the next trial, which 
could test a more interesting and a more effective agent.
    Senator Specter. That is something that this subcommittee 
is very interested in, how rapid it can be and how fast we can 
provide these answers. There are many, many women out there who 
want the answers.

                SUMMARY STATEMENT OF DR. BERNARD FISHER

    We have in the hearing room today Dr. Bernard Fisher. 
Although he is not on the official witness list, Dr. Fisher, 
would you mind stepping forward. I would like to get your 
appraisal of this hearing today.
    Dr. Fisher was chairman and principal investigator of the 
national surgical adjuvant breast and bowel project for 27 
years. In 1992, he initiated the world's first study to 
determine whether tamoxifen can prevent breast cancer in women 
at high risk.
    There have been some professional questions raised and Dr. 
Fisher has emerged the victor. Sometimes the courts have to 
adjudicate medical controversies, and there was a very sizable 
award in addition.
    Our question today is on the medical aspect. Dr. Fisher, 
you were in my office along with others trying to mediate and 
trying to find an answer to some of those problems. Today the 
focus is on trying to prevent breast cancer.
    The subcommittee would like your evaluation of these 
studies.
    Dr. Fisher. Well, Senator Specter, I thank you very much 
for allowing me to make a few comments. I consider the current 
findings to be the most important of the contributions which I 
and my colleagues have made during my 40 years of using large, 
randomized clinical trials to improve the status of women with 
breast cancer. The results presented here today permit the 
opening of a new door which permits us to move forward in an 
entirely new direction of breast cancer research.
    Where that journey will take us remains to be determined. 
But it will take us forward in our common effort to eliminate 
breast cancer. This situation is entirely similar to that which 
has occurred as a result of identification of the changes in 
BRCA I and BRCA II genes. In both situations, a multiplicity of 
new questions have been raised which must be answered. In both 
the precise way in which the findings will be integrated into 
strategies that will better women must be and will be defined.
    From my perspective, I see a nexus between these two recent 
developments, the BRCA I and BRCA II genes and the 
identification of these alterations which put a woman at high 
risk for the disease and the presence of agents which can 
possibly markedly decrease that risk.
    For these events now there exist possible alternatives for 
women who are considering removal of both breasts to prevent a 
breast cancer. Just as it is likely that there will be 
observations of other genes----
    Senator Specter. Dr. Fisher, permit me to interrupt you for 
one question. Do you think there are circumstances under which 
removal of both breasts is an appropriate effort made to 
prevent breast cancer?
    Dr. Fisher. I think there are circumstances, but in my view 
they are few and far between.
    Senator Specter. It sounds very drastic to me. You say 
there are a few cases, but they are very rare.
    Dr. Fisher. Very rare.
    I think, just as there will be more genes discovered which 
relate to breast cancer, as we have said here today, there are 
going to be other drugs which will come along about which we 
need to know their relative merits.
    Senator Specter. Dr. Fisher, I am going to have to ask you 
to summarize in 2 minutes because there are about 3 minutes 
left to the vote.
    Dr. Fisher. Then I will just give it to you in 50 seconds.
    Senator Specter. Perfect.
    Dr. Fisher. Senator Specter, I am grateful for the funding 
that I have received from the Federal Government over the past 
40 years which made it possible for me and my associates to 
demonstrate that mutilating operations for breast cancer could 
be replaced by lumpectomy, that post-operative chemotherapy and 
hormonal agents can prolong the lives of many patients with 
breast cancer, and that now some women can have their breast 
cancers prevented.
    New lines of investigation are available. Much work must be 
done and ample funding is necessary to accomplish the goals. 
The goals of eliminating breast cancer as a terrible public 
health issue can only be achieved if we keep our collective 
eyes on the goal and work together without inappropriate 
divisiveness.
    Thank you, sir.
    Senator Specter. Thank you very much, Dr. Fisher, and thank 
you for all the service you have given to America and the world 
on this important subject.
    Dr. Fisher. Thank you.
    Senator Specter. We are going to conclude the hearing at 
this point rather than interrupting. We have what we call three 
back-to-back-to-back votes and it will take about 45 minutes. 
There is too much talent in this room to ask you to wait.
    We may have another hearing on this subject. In the 
interim, I would like to ask Dr. Klausner, Dr. Wolmark, and Dr. 
Varmus to submit to the subcommittee a definition as to a high 
risk patient so that we can have it on the record and we can 
promulgate it.
    I would also like you to give the subcommittee a written 
answer, Dr. Klausner and Dr. Wolmark, as to what might be done 
as to Ms. Wilson's suggestion. First, as to whether you agree 
with her that we need more minority participants and, second, 
as to how we can go about getting them.
    Ms. Pearson, I would appreciate it if you would submit to 
the subcommittee the qualifications you have articulated of the 
circumstances where you would opt on the side of giving 
tamoxifen. You have given some good cautionary signals. I would 
like you to amplify the answer which you had been giving as to 
where you would recommend that tamoxifen be given.
    Finally, Dr. Klausner, I would like as much specification 
as you can give as to what you think you could do at the 
National Cancer Institute if you had that figure which matched 
your druthers.
    I have already done this with Dr. Varmus, where he had a 
very distinguished assemblage of the directors of the various 
institutes in this room several weeks ago. To the extent that 
you can quantify it, Dr. Klausner, tell us where we might go 
with both tamoxifen and raloxifene. The subcommittee would 
appreciate that.
    [The information follows:]
                         Minority Participation
    Throughout the trial, several strategies were used to increase 
participation of women from racial and ethnic minority groups. These 
strategies included placing study-related recruitment materials in 
businesses and churches located in minority communities; collaborating 
with a minority-owned public relations firm to develop a structured 
media campaign targeting racial and ethnic minorities; developing and 
broadly disseminating a Public Service Announcement that featured 
singer Nancy Wilson; and communicating information to study sites about 
how other sites successfully reached racial and ethnic minorities.
    In the beginning of the study, the National Surgical Adjuvant 
Breast and Bowel Project (NSABP) tried several minority recruitment 
approaches on the BCPT which were marginally helpful. In August 1996, 
the NSABP began a Pilot Minority Recruitment Program (PMRP) for the 
BCPT. The goal of the PMRP was to increase minority enrollment in the 
BCPT by increasing communities' awareness of, and educating racial and 
ethnic minority populations about, the trial. This was thought to be 
best accomplished by funding a half-time community outreach coordinator 
(COC) dedicated to conducting community outreach. Selected sites 
employed a part-time COC who was representative of and had an 
understanding of the barriers to participating in clinical trials faced 
by various minority groups. The COCs fostered many relationships in 
their communities by offering personalized presentations on breast 
cancer risk factors, incidence, and survival rates and on clinical 
trials research. In less than a year, collaborations were formed as a 
result of presentations given at African American churches, community 
hospitals and health clinics, Hispanic health fairs, local chapters of 
Chi Eta Phi and Delta Sigma Theta Soroities, the Urban League, YWCA, 
AARP, and minority medical societies. Additionally, the COCs heightened 
awareness about the BCPT via an article that appeared in Essence 
magazine and via newsletters that reached thousands of physicians in 
Chicago and the constituents of state representatives in Pennsylvania.
    The PMRP has been the most effective recruitment strategy to date 
and will serve as the model for minority recruitment for future 
prevention trials. The NSABP has recently received approval for full 
funding of these currently half-time COCs and hopes to add more 
minority sites that will reach not only the African American community, 
but also the Hispanic community as they continue to strengthen minority 
outreach for the upcoming breast cancer prevention trial with 
raloxifene.
                               HIGH RISK
    The following information will outline what the NSABP used as a 
standard to classify what constitutes ``high risk'' for breast cancer 
among women ages 35 to 59:
  --To enroll in the study, women between 35 and 59 years of age needed 
        to have a risk of developing breast cancer within the next five 
        years that was equal to or greater than the average risk for 
        60-year-old women. This increased risk was determined in one of 
        two ways. Women diagnosed as having lobular carcinoma in situ, 
        a condition that is not cancer but indicates an increased 
        chance of developing invasive breast cancer, were eligible 
        based on that diagnosis alone. The risk for other women was 
        determined by a computer calculation based on the following 
        factors:
  --Number of first-degree relatives (mother, daughters, or sisters) 
        who had been diagnosed as having breast cancer; whether a woman 
        had any children and her age at her first delivery; the number 
        of times a woman had breast lumps biopsied, especially if the 
        tissue was shown to have a condition known as atypical 
        hyperplasia; and the woman's age at her first menstrual period.
  --For example, a 35-year-old woman would have to have two or more 
        first-degree relatives with breast cancer and a personal 
        history of at least one benign breast biopsy or a diagnosis of 
        lobular carcinoma in situ.
  --A 45-year-old woman would have to have one or more first-degree 
        relatives with breast cancer and a personal history of at least 
        one benign breast biopsy or a diagnosis of lobular carcinoma in 
        situ.
  --A 55-year-old woman would have to have one or more first-degree 
        relatives with breast cancer or a personal history of at least 
        one benign breast biopsy or a diagnosis of lobular carcinoma in 
        situ.
  --Women 60 years of age or older were eligible for the BCPT based on 
        age alone because many diseases, including breast cancer, occur 
        more often in older persons. The risk of developing breast 
        cancer increases with age, so breast cancer occurs more 
        commonly in women over 60 years of age. The risk of developing 
        heart disease or osteoporosis also increases with age, and 
        those diseases are also being studied in the BCPT.
    The NCI is in the process of developing and testing a risk/benefit 
assessment tool for physicians to use in counseling their patients 
about whether or not to take tamoxifen for breast cancer prevention. 
This will be posted on the NCI Cancer Trials web site and will also be 
available through the Cancer Information Service. In the meantime, 
health care providers who want information about how to assess the 
breast cancer risk of an individual woman may contact NCI via email at 
[email protected] or by calling the Cancer Information Service at 1-800-4-
CANCER (1-800-422-6237) and following the prompts for ordering 
materials. The model will be refined over time, and requesters may sign 
up to be notified when a more refined version is available.

                               RALOXIFENE

    The NSABP is planning a second breast cancer prevention trial, 
tentatively scheduled to begin in the fall of 1998. The trial would 
involve 20-25,000 postmenopausal women who are at least 35 years old 
and are at increased risk for developing breast cancer. The study would 
compare tamoxifen to raloxifene, a drug that was recently approved by 
the FDA for treating osteoporosis and is thought to have the same 
benefits as tamoxifen but possibly fewer side effects. The primary aim 
of the trial is to test whether long-term raloxifene therapy is 
effective in preventing the occurrence of invasive breast cancer in 
postmenopausal women having an increased risk of developing the 
disease. A secondary aim is to establish the net effect of raloxifene 
therapy. Data will also be collected on cardiovascular and fracture 
endpoints and for all toxicities and side effects. This information 
will allow a comprehensive benefit/risk assessment to be derived for 
the use of raloxifene as a chemopreventive agent. We estimate that the 
cost of this study will be approximately $80 to 100 million. Women will 
be informed about the study through similar channels as were used for 
the BCPT. In addition, we will be strengthening the minority enrollment 
programs as outlined earlier.

                         CONCLUSION OF HEARING

    Senator Specter. Dr. Varmus, did you have one more word?
    Dr. Varmus. Just that Dr. Klausner, of course, was in the 
room at that time and submitted along with other Institute 
Directors a statement about his ambitions with increased funds.
    Senator Specter. Well, if you have any supplement, we will 
take that.
    Thank you all very much for being here, we appreciate it, 
that concludes our hearing. The subcommittee will stand in 
recess subject to the call of the Chair.
    [Whereupon, at 2:50 p.m., Tuesday, April 21, the hearing 
was concluded, and the subcommittee was recessed, to reconvene 
subject to the call of the Chair.]

                                   -