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Selective Estrogen Receptor Modulators (SERMs) are a group of drugs that act on the estrogen receptor. Tamoxifen is a SERM that selectively blocks the effect of estrogen on breast tissue. It was approved by the FDA in 1998 for decreasing breast cancer risk in high-risk women. A large clinical trial, Study of Tamoxifen and Raloxifene (STAR), found that women who took tamoxifen for 5 years lowered their breast cancer risk by 50%. The results of this study were updated in 2010 with an 81 month analysis (including 60 months of treatment and 21months follow-up). After 5 years of treatment, 50% breast cancer risk reduction persisted post treatment. This is supported by data from several placebo control tamoxifen prevention trials, including International Breast Cancer Intervention Study I (IBIS-I), that showed risk reduction of breast cancer persists for at least 5-10 years beyond 5-8 year course of treatment.
The STAR trial identified women at high-risk for breast cancer according to a model that predicts breast cancer risk known as the Gail Model. The Gail Model does not take into account certain aspects of hereditary breast and ovarian cancer. Smaller studies looking at tamoxifen for breast cancer prevention in women with BRCA mutations have been inconclusive.
In a study of 19 women with BRCA mutations, women with BRCA2 mutations who took tamoxifen had a lower breast cancer risk. In the same study, women with BRCA1 mutations who took tamoxifen did not have any decrease in breast cancer risk. However, these results were based on a small sample size (11 and 8 women respectively) and were not statistically significant.
Studies of BRCA mutation carriers who were diagnosed with cancer in one breast and took tamoxifen demonstrated a reduced risk for breast cancer in the other breast. One such study showed tamoxifen lowered the risk for a new breast cancer in the other breast by about 40% in women with BRCA1 mutations and by about 25% in women with BRCA2 mutations. However, it is uncertain if the same risk-lowering affect applies to BRCA mutation carriers who have not had cancer or to BRCA mutation carriers whose prior breast cancers did not express estrogen or progesterone receptors.
Tamoxifen may protect bone density and reduce osteoporosis risk in postmenopausal women who cannot take hormone replacement.
Tamoxifen has been shown to cause some serious side effects and risks. Women who take this medication are at an increased risk for developing uterine cancer, thromboembolic events, and thickening of the uterus known as endometrial hyperplasia. Tamoxifen can also increase the risk of cataracts and blood clots, including serious blood clots particularly in women who smoke or have other risk factors. Tamoxifen may also have less serious side effects such as hot flashes and vaginal dryness.
Overall, tamoxifen is considered an effective preventative strategy for healthy women at increased risk for breast cancer. It has been shown to have an excellent safety profile with only a modest number of serious side effects over three decades of use.
Experts do not all agree that tamoxifen is appropriate for preventing breast cancer in women with BRCA1 mutations. Women who consider tamoxifen to lower their risk for breast cancer should discuss the benefits, risks and limitations with their health care team, including experts in managing high-risk women.