Association of Risk-Reducing Surgery With Cancer Risks and Mortality in BRCA Mutation Carriers—Reply

In Reply: Dr Heemskerk-Gerritsen and colleagues ask whether there is an age effect on the association of RRSO with second breast cancer events. A decrease in contralateral breast cancer risk has been reported in several studies. We postulated that the absence of an association with second primary breast cancer seen in our study might be secondary to confounding by treatment effects. However, a later age at RRSO might also be a contributor. In BRCA1 mutation carriers, RRSO was associated with a lower risk of first breast cancer in women younger than 50 years, but not older than 50 years. We have subsequently examined risk of second (contralateral) breast cancer after RRSO, but found no association with second primaries by age in either BRCA1 or BRCA2 mutation carriers. In BRCA1 mutation carriers, risk of a second breast cancer was nonsignificantly lower in carriers with RRSO younger than 50 years (hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.42-1.63), but not older than 50 years (HR, 1.34; 95% CI, 0.54-3.28). Data regarding chemotherapy-induced menopause were not available, nor can we directly address the hypothesis that the lack of an association might be explained by treatment effects.