Second primary cancer risks after breast cancer in BRCA1 and BRCA2 pathogenic variant carriers

Second primary cancer (SPC) risks after breast cancer (BC) in BRCA1/BRCA2 pathogenic variant (PV) carriers are uncertain. Follow-up of survivors of BC who were tested in National Health Service Clinical Genetic centers in England (1,840 BRCA1 and 1,750 BRCA2 PV carriers among 25,811 tested women) found that BRCA1 PV carriers compared to the general population had elevated risk of contralateral BC, ovarian SPC, combined nonbreast/ovarian SPC, colorectal SPC, and endometrial SPC, while BRCA2 PV carriers had elevated risks of contralateral BC, ovarian SPC, pancreatic SPC, and nonbreast/ovarian SPC. Compared with females without BRCA1/2 PVs on testing, BRCA1 carriers had elevated risk of contralateral BC, ovarian SPC, combined nonbreast/ovarian SPC, and colorectal SPC, whereas BRCA2 PV carriers had elevated risk of contralateral BC, ovarian SPC, and pancreatic SPC. Ten-year cumulative risk of contralateral BC, ovarian SPC, and combined nonbreast/ovarian SPC risks were 16%/6.3%/7.8% for BRCA1 PV carriers, 12%/3.0%/6.2% for BRCA2 PV carriers, and 3.6%/0.4%/4.9% for noncarriers. Male BRCA2 PV carriers had higher risks of contralateral BC and prostate SPC than noncarriers. The authors conclude that survivors of BC carrying BRCA1 or BRCA2 PVs are at high SPC risk. They may benefit from enhanced surveillance.