Here's a text of some of the C-SPAN remarks. The first is by Norman Walmark:
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% 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 (Figure 1). 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 (Figure 2). 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% 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 ( cancertrials.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
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.
###
Statement of
Helene Wilson
Participant
National Surgical Adjuvant Breast and Bowel Project (NSABP)
Breast Cancer Prevention Trial
before the
Senate Appropriations Subcommittee
on
Labor, Health and Human Services
Education and Related Agencies
April 21, 1998
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..........
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.
### |
