- LOS ANGELES, CA
-- October 5, 1999 -- Women whose breast cancer is treated with tamoxifen
face a heightened risk for endometrial cancer, with that risk compounded
in women who also have received estrogen replacement therapy or who are
obese, according to a study led by University of Southern California researchers.
- Leslie Bernstein, Ph.D., professor of preventive medicine
at the Keck School of Medicine of the University of Southern California
and USC/Norris Comprehensive Cancer Center, and colleagues present these
findings in the Oct. 6 issue of the Journal of the National Cancer Institute.
- Doctors prescribe tamoxifen, a synthetic hormone, to
women as a breast cancer treatment because of its proven benefits for blocking
a recurrence of the disease, reducing the likelihood of a second breast
cancer developing in the opposite breast and extending patients' survival.
It is also under study as a preventive agent against breast cancer in women
at high risk for the disease. However, this study indicates the same drug
increases the risk of endometrial cancer, the most frequent gynecologic
cancer in women.
- "Because tamoxifen is a critical therapeutic option
for breast cancer patients, we need to understand its other effects on
the body," Bernstein said. "Although we have known that endometrial
or uterine cancer develops in a tiny proportion of women taking tamoxifen,
we have not known which particular groups of women are at greatest risk
of this disease."
- Overall, the authors report that tamoxifen therapy for
breast cancer increased the risk of endometrial cancer by about 50 percent.
The longer women are on tamoxifen therapy, the greater their risk: women
with more than five years of exposure to tamoxifen were four times more
likely to develop endometrial cancer than women who did not use tamoxifen.
But a woman's risk of endometrial cancer also varies according to other
- Factors already known to either increase or decrease
women's risk of endometrial cancer include: birth control pills, which
reduce risk; estrogen therapy, which can increase risk unless taken in
combination with progestin therapy; and obesity, which increases risk.
These factors affected the endometrial cancer risk of breast cancer patients
in this study.
- Tamoxifen increased endometrial cancer risk, primarily
among women who had previously used estrogens. The risk of endometrial
cancer was more than three times higher among women who had taken both
estrogen replacement therapy and tamoxifen than among women who had not
taken either drug. And among women who had previously been on estrogen
replacement therapy, those who took tamoxifen for more than five years
were five and a half times as likely to develop endometrial cancer as women
who had not been prescribed tamoxifen.
- The risk associated with tamoxifen use was stronger among
heavier women than among thinner women, with risk the highest for women
who both were overweight and had a history of taking estrogen replacement
- Tamoxifen has been found to have estrogen-like effects
on the uterus, which may account for women's increased endometrial cancer
risk. Researchers believe obesity may cause greater exposure to estrogen
in the uterus, as well.
- Endometrial cancer occurs far less frequently than breast
cancer, and decisions about whether to prescribe tamoxifen should be considered
in light of this differential in risk, Bernstein said. In the United States,
recent population statistics show that 110 of every 100,000 women develop
breast cancer annually. This is five times greater than the rate of endometrial
cancer, which is 21 cases in every 100,000 women. Women also are more likely
to die from breast cancer than from endometrial cancer. The chances that
a woman will die of breast cancer each year are 26 per every 100,000 women
in the United States, far higher than the three per every 100,000 women
who die each year of endometrial cancer.
- "We have confirmed the findings of other studies
showing that tamoxifen increases the risk of uterine cancer; and most importantly,
we have found that women who have used estrogens and who are overweight
have the greatest risk when using tamoxifen," Bernstein said. "Our
results suggest that physicians should be particularly vigilant in monitoring
tamoxifen-treated patients with these additional risk factors."
- Bernstein noted that the risk of endometrial cancer must
be balanced against tamoxifen's proven benefits in breast cancer treatment
and its effectiveness in reducing the incidence of breast cancer among
women at high risk for that cancer.
- The researchers conducted the study with 324 patients
with endometrial cancer who had previously been treated for breast cancer
and 671 similar patients with breast cancer who did not develop endometrial
- Leslie Bernstein, Dennis Deapen, James R. Cerhan, Stephen
M. Schwartz, Jonathan Liff, Erin McGann-Maloney, Jeffrey A. Perlman and
Leslie Ford, "Tamoxifen Therapy for Breast Cancer and Endometrial
Cancer Risk," Journal of the National Cancer Institute, vol. 91, no.
19, pp. 1654-1662.