A new study has revealed that survivors of breast cancer (BC) with BRCA1 or BRCA2 pathogenic variants (PVs) face significantly higher risks of developing second primary cancers (SPCs). By linking genetic testing data with national health records, the study tracked 25,811 females and 480 males diagnosed with BC between 1995 and 2019, estimating both relative and absolute risks for developing SPCs. There were 1,840 BRCA1 and 1,750 BRCA2 female PV carriers.
The results show that BRCA1 female carriers are particularly at risk for contralateral breast cancer (CBC), ovarian cancer, and other cancers, including colorectal and endometrial cancers. For instance, BRCA1 carriers had a 44 times higher risk for ovarian cancer (SIR: 44.0 [95% CI: 31.4–59.9]) and an almost five-fold increased risk for colorectal cancer (SIR: 4.80 [95% CI: 2.62–8.05]) compared to the general population. BRCA2 carriers also had elevated risks, including a seven-fold increased risk for CBC (SIR: 7.70 [95% CI: 5.45–10.6]) and a five-fold higher risk for pancreatic cancer (SIR: 5.42 [95% CI: 2.09–12.5]).
When compared to non-carriers, BRCA1 carriers were found to have a significantly higher risk of CBC (HR: 3.60 [95% CI: 2.65–4.90]), ovarian (HR: 33.0 [95% CI: 19.1–57.1]), and colorectal cancers (HR: 2.93 [95% CI: 1.53–5.62]), while BRCA2 carriers had elevated risks for CBC (HR: 2.40 [95% CI: 1.70–3.40]), ovarian (HR: 12.0 [95% CI: 6.70–21.5]), and pancreatic cancers (HR, 3.56 [95% CI, 1.34–9.48]).
In males, BRCA2 carriers showed a notably higher risk of CBC and prostate cancer. The study suggests that BC survivors with BRCA1 and BRCA2 PVs may benefit from enhanced surveillance and preventive measures to manage these elevated risks.
These findings underscore the need for tailored monitoring strategies to help reduce the likelihood of second cancers in these high-risk individuals.
Helena Bradbury, EMJ
Reference
Allen I et al. Second primary cancer risks after breast cancer in BRCA1 and BRCA2 pathogenic variant carriers. 2024;doi: 10.1200/JCO.24.01146.
