Oral contraceptives, salpingo-oophorectomy and hormone replacement therapy in BRCA1–2 mutation carriers

Abstract

Germline mutations in BRCA1 or BRCA2 genes predispose to hereditary breast and ovarian cancers. The estimated lifetime risk of breast cancer in BRCA1 mutation carriers ranges from 50% to 80% while the estimated lifetime risk of ovarian cancer ranges from 20% to 65%. Although breast cancer risk is similar in women who inherit BRCA2 mutations the lifetime risk of ovarian cancer is approximately 20%. In the general population reproductive factors (such as parity age at menopause use of exogenous steroid hormones as contraceptives or after menopause) influence the risk of breast and ovarian cancer. In BRCA mutation carriers these issues are much more complicated and not completely understood. Nonetheless a growing number of data show that estrogens may modulate the risk of breast cancer in women with BRCA mutations. In these women estrogens may increase the probability of mutation due to enhanced proliferation and direct genotoxic effects of estrogen metabolites. Women carrying BRCA1 and BRCA2 mutations face difficult decisions during the reproductive life. In the younger age period they may be reluctant to using oral contraceptives (OCs) for the possible influence of these compounds on breast cancer incidence. After completion of childbearing they may be offered the option of prophylactic oophorectomy that is associated with a strong reduction of cancer risk but also with the early onset of menopausal symptoms and the long-term consequences of estrogen deprivation. (excerpt)