Germline pathogenic variants for breast cancer also increase contralateral breast cancer risk

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 influence 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 is not well defined. Previously, the CARRIERS study provided estimates of the prevalence and risk of the variants ATM, BRCA1, BRCA2, CHEK2, 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 genetic variants on a subsequent contralateral breast cancer (CBC) event. Prof. Siddhartha Yadav (Mayo Clinic, MN, USA) presented the results [2].

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 3 times higher in pre-menopausal patients compared with post-menopausal patients. CBC in carriers who were over 65 years at their first breast cancer diagnosis (n=153) was rare, with only 3 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 personalised approach to CBC risk management strategies in germline ATM, BRCA1, BRCA2, CHEK2, and PALB2 pathogenic variant carriers based on relevant demographic and tumour characteristics,” concluded Prof. Yadav.

1. Hu C, et al. N Engl J Med. 2021;384:440–451.
2. Yadav S, et al. Population-based estimates of contralateral breast cancer risk among carriers of germline pathogenic variants in ATM, BRCA1, BRCA2, CHEK2 and PALB2. Abstract GS4-04, SABCS 2022, 6–10 December, San Antonio, TX, USA.

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Posted on 1 February, 2023