More Evidence of Tamoxifen's Benefit for Women at Risk of Breast Cancer
Key Words: breast cancer, prevention,
tamoxifen. (Definitions of many terms
related to cancer can be found in the Cancer.gov
Dictionary.)
Preliminary results from a large international trial, the International Breast
Cancer Intervention Study (IBIS), provide additional evidence that the drug
tamoxifen (Nolvadex®) can reduce the incidence of breast cancer in women at
increased risk for the disease. Women taking tamoxifen experienced one third
fewer breast cancers than women who took a placebo (dummy pill), researchers
announced on March 20, 2002, at the 3rd European Breast Cancer Conference in
Barcelona, Spain. [Editor's note: These results were subsequently published in
the Sept. 14, 2002, issue of The Lancet;
see the journal abstract.]
These findings are similar to those of the National Cancer Institute's Breast
Cancer Prevention Trial (BCPT),
a large U.S. study that in 1998 found a 49 percent reduction in new cases of
breast cancer among participants who took tamoxifen for five years. Two other
smaller European trials failed to find a lower incidence of breast cancer among
women who took tamoxifen compared with those who took a placebo.
Although the new findings are encouraging, say IBIS researchers, they do not
offer a conclusive answer to whether the benefits of tamoxifen outweigh the
side effects in healthy women.
As in BCPT, IBIS found a two- to three-fold increase in risk for both
endometrial cancer and serious blood clots
among women who took tamoxifen. "Women who are at increased risk for
breast cancer should talk with their doctors about the risks and benefits of
taking tamoxifen," said Worta McCaskill-Stevens, M.D., of the Division of
Cancer Prevention at the National Cancer Institute (NCI).
IBIS involves 7,000 healthy women in four European countries, Australia and New
Zealand who have been
randomly assigned to receive either
tamoxifen or a placebo. Eligibility was determined by family history of the
disease or a history of atypical hyperplasia, a benign (noncancerous) breast
condition that is believed to increase risk for invasive disease, particularly
in women with a family history of breast cancer.
The study found a similar reduction in breast cancer incidence regardless of
age, risk level or use of
hormone replacement therapy. (In the BCPT,
participants were not permitted to use hormone replacement therapy.) However,
in both trials, the reduction in incidence was seen only for breast cancers
sensitive to the hormone
estrogen.
In about seven out of 10 cases of breast cancer, the cancer cells have areas on
their surface called
receptors to which hormones such as
estrogen and
progesterone attach, providing fuel for the
cells' growth into a tumor. Tamoxifen works by disrupting estrogen's ability to
help cancer cells grow.
Participants in IBIS will continue to be followed to see if a particular
high-risk group can be identified for whom the benefits of tamoxifen clearly
outweigh the risks, said principal investigator Professor Jack Cuzick of Cancer
Research UK, which is coordinating the study.
"Tamoxifen is a medically proven intervention, but it is not perfect. Women
who are at an increased risk of breast cancer need options for preventing this
disease with a minimum of side effects," said Leslie Ford, associate
director for clinical research in NCI's Division of Cancer Prevention.
"The NCI's Study of Tamoxifen and Raloxifene is a concerted effort to find
such an option."
In the United States, the Study of Tamoxifen and Raloxifene (STAR)
is now evaluating whether the osteoporosis prevention drug
raloxifene (Evista®) reduces the risk
of developing breast cancer as effectively as tamoxifen. STAR began in 1999 and
will follow women for five to 10 years. Postmenopausal women who have an
elevated risk of breast cancer are being recruited to participate in STAR; as
of February 28, 2002, nearly 13,000 women had enrolled. A total of 22,000 women
will be recruited, making STAR one of the largest breast cancer prevention
studies ever conducted.
Unlike tamoxifen, raloxifene does not appear to increase the risk of endometrial
cancer, said McCaskill-Stevens. "If raloxifene is shown to be as effective
as tamoxifen at reducing breast cancer incidence, it would provide women at
increased risk of breast cancer with a prevention option that has fewer side
effects."
Like tamoxifen, however, raloxifene increases risk for blood clots. And because
the safety of raloxifene in premenopausal women has not been established,
enrollment in STAR is limited to women who have passed menopause.
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