Estrogen is a well known promoting factor of sporadic breast carcinoma. With T he cumulative risk of breast carcinoma in carriers of BRCA1/ BRCA2 mutations ranges from 45% to 84% by age 70 years. 1,2Knowledge of carcinogenesis and promoting factors that modulate the risk of breast carcinoma in BRCA1/BRCA2 mutation carriers, thus, is essential for preventive decision making.Estrogens play a crucial role in the growth of normal and tumor mammary cells. There are data emerging from clinical studies showing that current and recent use of combined estrogens and progestins as hormone-replacement therapy (HRT) significantly increases the risk of sporadic breast carcinoma.3-5 Conversely, suppressive therapies, such as adjuvant antiestrogens and aromatase inhibitors, reduce the risk of contralateral breast carcinoma in women who present with breast carcinoma. 6,7 The National Surgical Adjuvant Breast Project (NSABP) P-1 study of high-risk women who had a familial history of breast carcinoma or who presented with proliferative benign mammary lesions revealed that chemoprevention by tamoxifen reduced the risk of breast carcinoma by 49% (P Ͻ 0.00001) during the observation period. 8 Therefore, the potential effect of estrogens in modifying the risk of breast carcinoma in patients with a BRCA mutation is of clinical relevance. Two important questions in clinical practice are 1) could estrogen therapy be prescribed in women with a familial risk of breast carcinoma; and 2) do estrogen-suppression therapies reduce the risk of carcinoma in these women? 1567
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