First, since prophylactic oophorectomy reduces the risk of breast cancer in BRCA1 mutation carriers by up to 50% [34], we included this observation as a time-dependent covariate in the analysis, and a significant association similar to the one shown above was revealed: HR = 1.09 (95% CI 1.03–1.16), ptrend = 4.5×10−4. This evidence concerns the gene BRCA1 and breast carcinoma.