[Senate Hearing 105-561]
[From the U.S. Government Publishing Office]
S. Hrg. 105-561
TAMOXIFEN AND BREAST CANCER
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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
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senate
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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
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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
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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
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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.]
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