Tamoxifen Found To Increase Risk Of Endometrial Cancer

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 characteristics.

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 therapy.

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 cancer.