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Background  The effect of risk-reducing salpingo-oophorectomy (RRSO) on breast cancer risk for  BRCA1  and  BRCA2  mutation carriers is uncertain. Retrospective analyses have suggested a protective effect but may be substantially biased. Prospective studies have had limited power, particularly for  BRCA2  mutation carriers. Further, previous studies have not considered the effect of RRSO in the context of natural menopause.    Methods  A multi-centre prospective cohort of 2272  BRCA1  and 1605  BRCA2  mutation carriers was followed for a mean of 5.4 and 4.9 years, respectively; 426 women developed incident breast cancer. RRSO was modelled as a time-dependent covariate in Cox regression, and its effect assessed in premenopausal and postmenopausal women.    Results  There was no association between RRSO and breast cancer for  BRCA1  (HR = 1.23; 95% CI 0.94–1.61) or  BRCA2  (HR = 0.88; 95% CI 0.62–1.24) mutation carriers. For  BRCA2  mutation carriers, HRs were 0.68 (95% CI 0.40–1.15) and 1.07 (95% CI 0.69–1.64) for RRSO carried out before or after age 45 years, respectively. The HR for  BRCA2  mutation carriers decreased with increasing time since RRSO (HR = 0.51; 95% CI 0.26–0.99 for 5 years or longer after RRSO). Estimates for premenopausal women were similar.    Conclusion  We found no evidence that RRSO reduces breast cancer risk for  BRCA1  mutation carriers. A potentially beneficial effect for  BRCA2  mutation carriers was observed, particularly after 5 years following RRSO. These results may inform counselling and management of carriers with respect to RRSO.

breast cancer research

Risk-reducing salpingo-oophorectomy, natural menopause, and breast cancer risk: an international prospective cohort of BRCA1 and BRCA2 mutation carriers