Tamoxifen and endometrial cancer.

Tamoxifen is one of the most promising breast cancer treatments available, but no one fully understands how it works. In some ways, it appears to be estrogen's "good twin." Because of a strong structural resemblance, it can fool the estrogen receptors on breast cancer cells to accepting it instead of estrogen, thereby blocking the hormone from stimulating their growth. Yet, like estrogen, it increases bone density and reduces the risk of heart attack.

However, as recent results from a major study indicate, tamoxifen shares one of estrogen's nastier traits -- it increases the risk of endometrial cancer by causing the cells lining the uterus to proliferate. A report from the National Surgical Adjuvant Breast and Bowel Project (NSABP) indicates that for women who are undergoing treatment for breast cancer, the risk of developing endometrial cancer increases 2.3 times if their therapy includes tamoxifen. Although the increased risk is similar to that detected in previous investigations, the NSABP was the largest such study and the only one in which participants were randomized to receive either tamoxifen or placebo following surgery for malignant tumors that were confined to the breast. For the women who took tamoxifen in the study, the risk of developing endometrial cancer within 5 years of treatment was 0.6% -- a rate similar to that found in earlier studies; the comparable risk is about 0.3% among women treated for breast cancer who have not undergone systemic therapy.

At the same time, the women who had taken tamoxifen had a much lower risk of breast-cancer recurrence. During a 5-year follow-up period, only 14.6% of the women who took tamoxifen -- compared to 26.8% of those who didn't -- had new evidence of breast cancer. The rate of other cancers didn't vary significantly between the two groups. The researchers calculated that tamoxifen was responsible for a 38% reduction in the overall risk of developing a second cancer within 5 years. The report appeared in the April 6, 1994, issue of the Journal of the National Cancer Institute.

While the results support earlier evidence that tamoxifen increases endometrial-cancer risk, they provide some reassurance that the annual risk -- about 12 in 10,000-- is still quite low. Moreover, the endometrial tumors in the women studied were not more aggressive than usual, as once hypothesized. Thus, the benefits of tamoxifen treatment seem to greatly outweigh the risks for women with breast cancer.

But is the increased endometrial-cancer risk justified for healthy women who, because they are at high risk for breast cancer, are taking tamoxifen to prevent breast cancer in NSABP studies? The study's leaders believe it is. At 2.3%, the risk of a tamoxifen-induced endometrial cancer, which is less lethal than breast cancer, is only slightly higher than the earlier estimate of 2.0% Thus, they maintain, the possible benefits still exceed the projected risks.

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