Case-control study of breast cancer susceptibility gene sequence variation and development of contralateral breast cancer

Heterogeneity in development of estrogen receptor (ER)-specific first primary breast cancer exists due to deleterious germline variants in moderate- to high-penetrance breast cancer susceptibility genes, but it is unknown if these associations occur in ER-specific contralateral breast cancer (CBC). Case-control analysis of 1290 CBC and matched unilateral breast cancer patients in the population-based WECARE study found that the rate of ER-positive CBC was 5 to 6 times higher in women with deleterious variants in BRCA2, ATM, and CHEK2. The rate of ER-negative CBC was 26 times higher in women with deleterious BRCA1 variants. The authors conclude that in this study, deleterious variants in breast cancer susceptibility genes were associated with differential rates of ER-specific CBC subtypes, providing further evidence of distinct etiologies of CBC subtypes.