👉Tamoxifen has been shown to reduce breast cancer risk by nearly 50% even for women with up to three first-degree relatives with breast cancer but has not yet been shown to improve survival.
👉Because tamoxifen is associated with an increased risk of endometrial cancer and thromboembolic events, especially in postmenopausal women, its safety profile is better in premenopausal women.
👉Chemoprevention options for postmenopausal women also include raloxifene, exemestane, and anastrozole.
👉These estrogen and estrogen response manipulators preferentially reduce the risk of hormone-sensitive breast cancer, so they may be most appropriate for women with gene mutations associated with a predominance of hormone-sensitive breast cancer, such as BRCA2, PALB2, CHEK2, and TP53.
👉However, there are data showing a 42% to 50% reduction in the risk of contralateral breast cancer in BRCA1 mutation carriers, a group that is at greatest risk for estrogen receptor–negative breast cancer.
👉It should be noted, however, that data from the National Surgical Adjuvant Breast and Bowel Project (NSABP) P1 Breast Cancer Prevention Trial suggested that tamoxifen reduced risk in BRCA2 but not BRCA1 carriers.
👉The number of mutation carriers included in this trial was quite small, so this conclusion may be suspect.
👉Chemoprevention can reasonably be considered for any high-risk woman, but the age distribution of breast cancer risk, the Food and Drug Administration statements approving tamoxifen for women over 35 years of age, and a trend toward later age at childbearing make chemoprevention an uncommon choice among genetically high–risk patients.
👉Oral contraceptive use is convincingly associated with a 50% reduction in ovarian cancer risk among BRCA1 and BRCA2 gene mutation carriers.
👉The effects of modern, low-dose oral contraceptives on breast cancer risk are uncertain as available data are conflicting.
👉NCCN guidelines do not specifically recommend oral contraceptives for ovarian cancer chemoprevention in mutation carriers, but genetics experts generally support 5 years of oral contraceptive exposure to reduce ovarian cancer risk.
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