Here's what NCI said about the study:
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. They also notified the 13,388
women participants of the findings so those women who had
been taking the 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 6 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 decision making 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 BCPT 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 3
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
BCPT Participant Advisory Board, said simply, "The results
are so profound that I'm speechless. We don't know where we
are going 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. Postmenopausal 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 breast lumps
biopsied, especially if the tissue was shown to have a
condition known as atypical hyperplasia
The woman's age at her first menstrual period; and .
Whether a woman has had a type of noninvasive breast
cancer known as lobular carcinoma in situ.
One of the most widely prescribed cancer drugs in the world,
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. |
