Oophorectomy after menopause and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

BACKGROUND To evaluate the effect of the cumulative number of ovulatory cycles and its contributing components on the risk of breast cancer among BRCA mutation carriers. METHODS We conducted a matched case-control study on 2,854 pairs of women with a BRCA1 or BRCA2 mutation. Conditional logistic regression was used to estimate the association between the number of ovulatory cycles and various exposures and the risk of breast cancer. Information from a subset of these women enrolled in a prospective cohort study was used to calculate age-specific breast cancer rates. RESULTS The annual risk of breast cancer decreased with the number of ovulatory cycles experienced (ρ = -0.69; P = 0.03). Age at menarche and duration of breastfeeding were inversely related with risk of breast cancer among BRCA1 (P(trend) < 0.0001) but not among BRCA2 (P(trend) ≥ 0.28) mutation carriers. The reduction in breast cancer risk associated with surgical menopause [OR, 0.52; 95% confidence interval (CI), 0.40-0.66; P(trend) < 0.0001] was greater than that associated with natural menopause (OR, 0.81; 95% CI, 0.62-1.07; P(trend) = 0.14). There was a highly significant reduction in breast cancer risk among women who had an oophorectomy after natural menopause (OR, 0.13; 95% CI, 0.02-0.54; P = 0.006). CONCLUSIONS These data challenge the hypothesis that breast cancer risk can be predicted by the lifetime number of ovulatory cycles in women with a BRCA mutation. Both pre- and postmenopausal oophorectomy protect against breast cancer. IMPACT Understanding the basis for the protective effect of oophorectomy has important implications for chemoprevention.