In women carrying a germline pathogenic variant for breast cancer, like BRCA1, BRCA2, or CHEK2, the risk for contralateral breast cancer is also increased, data from a sub-analysis of the CARRIERS study shows.


Currently, the precise influences of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2—as well as the effects of factors like age, menopausal status, race/ethnicity, and adjuvant endocrine therapy—on the risk to develop contralateral breast cancer are not well-defined. Previously, the CARRIERS study provided estimates of the prevalence and risk of variants ATM, BRCA1, BRCA2, CHE2, and PALB2 in the US population.1 In the same cohort, 15,104 women (14,444 non-carriers) treated with ipsilateral surgery for unilateral invasive breast cancer were followed to study the risk of these gene variants on a subsequent contralateral breast cancer (CBC) event. Dr. Siddhartha Yadav (Mayo Clinic) presented the results2 at the 2022 San Antonio Breast Cancer Symposium.

After a median follow-up of 11 years, 801 CBC events were observed. The 10-year cumulative incidence of CBC (from first breast cancer diagnosis) was significantly increased in carriers versus non-carriers of BRCA1 (23% vs 4.3%), BRCA2 (4.3% vs 17%), and CHEK2 (4.3% vs 8%), but not for carriers of ATM (4.3% vs 4.0%). For PALB2 carriers, the 10-year cumulative incidence of CBC was only increased in patients with ER-negative first breast cancer (5.4% vs 19.7%).

In all patients but ATM carriers, the 10-year cumulative incidence of CBC was approximately three times higher in pre-menopausal patients compared with post-menopausal patients. CBC in carriers who were older than 65 at first breast cancer diagnosis (n=153) was rare: three events at a median follow-up of 10 years. Race/ethnicity did not have any effect on CBC rates.

“The results of this study will aid in a more personalized approach to contralateral breast cancer risk management strategies in germline ATM, BRCA1, BRCA2, CHEK2, and PALB2 pathogenic variant carriers based on relevant demographic and tumor characteristics,” concluded Dr. Yadav.

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