Is BRCA1/BRCA2-related breast carcinogenesis estrogen dependent?

Abstract

Estrogen is a well known promoting factor of sporadic breast carcinoma. With regard to hereditary breast carcinoma, such as in BRCA1/BRCA2 syndromes, to date, the effects of estrogens on risk modification are not clear. Several studies have shown that prophylactic oophorectomy may decrease the risk of breast carcinoma in BRCA1/BRCA2 mutation carriers. Moreover, adjuvant tamoxifen therapy for primary breast carcinoma appears to diminish the risk of a second breast malignancy in BRCA1 mutation carriers. Conversely, exogenous estrogens, such as oral contraceptives, may increase the risk of breast carcinoma in familial breast cancer, as suggested by clinical studies. Paradoxically, the majority of BRCA1-related breast carcinomas are negative for ER. There is some biologic evidence of interactions between estrogens and BRCA proteins. BRCA1 expression could be induced by estradiol in experimental models, whereas recent studies indicate that BRCA1 modifies the regulatory effects of the estrogen receptor (ER) alpha (ERalpha). Prospective studies will be required to estimate the potential benefits of estrogen suppression therapies for the prevention and adjuvant treatment of BRCA1/BRCA2-related breast carcinomas.