Revisiting the Evidence for Breast Cancer Risk Reduction for Salpingo-Oophorectomy in BRCA1 and BRCA2 Mutation Carriers
There is little doubt that risk-reducing salpingo-oophorectomy (RRSO) reduces the risk of tubal and ovarian cancer, its impact on the risk of breast cancer is a bit uncertain. Whereas some studies report up to a 50% breast cancer risk reduction, these studies have been subject to a variety of biases. On the other hand, Heemskerk-Gerritsen et al. found no evidence of such a risk reduction1. In a recent publication by Mavaddat et al. detailed the results of an international prospective multi-center cohort of 2272 BRCA1 and 1605 BRCA2 mutation carriers. They examined the association of breast cancer risk and RRSO. The study combined nationwide studies in the UK, Ireland, France, Netherlands, Austria, Australia, and New Zealand.
Of the total, 37% BRCA1 and 31% BRCA2 mutation carriers reported RRSO. The end of follow-up was 9.5 years. In the primary analysis, the hazard ratio (HR) for the association between RRSO and breast cancer risk was 1.23 for BRCA1 (95% CI 0.4-1.15) and 0.88 (95% CI 0.62-1.24). Of interest, the HR for RRSO carried out before 45 years old in BRCA2 patients was 0.68 (CI 0.4—1.15) compared to 1.07 (CI 0.69-1.64) when RRSO performed after age 45.
It is important to note that a protective association was noted for BRCA2 mutation carriers 5 years after RRSO (HR 0.51, CI 0.26-0.99). The HR estimates were slightly lower for premenopausal BRCA2 mutation carriers.
Conclusion: It is important to reliably estimate the effect of RRSO when counseling patients who are BRCA1 or BRCA2 mutation carriers. This study of over 3800 BRCA mutation carriers by Heemskerk- Gerritsen et al. is the largest prospective study to date. Overall, this study is inconsistent with other studies finding no significant association between RRSO and breast cancer risk. There was a suggestion that RRSO may be effective when carried out before the age of 45. In this cohort, it was consistent with a study by Kotsopoulas et al. who reported risk reduction only in women less than 452. A favorable impact on breast cancer risk was noted in BRCA2 mutation carriers at least 5 years from RRSO with an HR of 0.51 whereas the HR remained near 1.0 for BRCA1 carriers at all times since.
The authors note that the “results suggest that a protective effect of RRSO for BRCA2 mutation carriers may manifest five or more years after surgery. While we cannot rule out an effect of RRSO for BRCA1 mutation carriers, this effect is unlikely to be as large.”
Heemskerk-Gerritsen et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers; revisiting the evidence for risk reduction. J Natl Cancer Inst 2015; 107(5).
Kotsopoulos et al. Bilateral oophorectomy and breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 2017; 109 (1)