The following is a summary of “Contralateral Breast Cancer Risk Among Carriers of Germline Pathogenic Variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2,” published in the March 2023 issue of Oncology by Yadav, et al.
For a study, researchers sought to determine the risk of contralateral breast cancer (CBC) in women with germline pathogenic variants (PVs) in five genes: ATM, BRCA1, BRCA2, CHEK2, and PALB2.
The study analyzed 15,104 women who were followed prospectively in the CARRIERS study and underwent ipsilateral surgery for invasive breast cancer. The risk of CBC was estimated for women with PVs in each gene compared to those without PVs, using multivariate proportional hazard regression analysis that accounted for the competing risk of death and adjusted for patient and tumor characteristics. The primary analyses were conducted on the overall cohort and women from the general population. Secondary analyses examined associations by race/ethnicity, age at primary breast cancer diagnosis, menopausal status, and tumor estrogen receptor (ER) status.
The study found that women with germline BRCA1, BRCA2, and CHEK2 PVs and breast cancer had a significantly higher risk (hazard ratio > 1.9) of CBC. In contrast, only PALB2 PV carriers with ER-negative breast cancer had elevated risks (hazard ratio, 2.9). However, women with ATM PVs did not have a significantly increased risk of CBC. The study also found that African American PV carriers had similar risks of CBC as non-Hispanic White PV carriers. Among premenopausal women, the 10-year cumulative incidence of CBC was estimated to be 33% for BRCA1, 27% for BRCA2, 13% for CHEK2 PV carriers with breast cancer, and 35% for PALB2 PV carriers with ER-negative breast cancer. The 10-year cumulative incidence of CBC among postmenopausal PV carriers was 12% for BRCA1, 9% for BRCA2, and 4% for CHEK2.
Women diagnosed with breast cancer and known to carry germline PVs in BRCA1, BRCA2, CHEK2, or PALB2 have a substantially increased risk of CBC and may benefit from enhanced surveillance and risk reduction strategies.