Contralateral breast cancer risks for BRCA1, BRCA2, PALB2, CHEK2, and ATM pathogenic variant carriers: a meta-analysis

Meta-analysis of 2 large cohorts, gene-specific 5- and 10-year contralateral breast cancer risk estimation after ipsilateral breast cancer

This cohort meta-analysis estimates contralateral breast cancer (CBC) risk for carriers of pathogenic variants in BRCA1, BRCA2, PALB2, CHEK2, and ATM who have already had breast cancer. Cumulative 5- and 10-year risks are quantified gene by gene, showing a risk gradient between high-penetrance genes (BRCA1: >20% at 10 years) and moderate-penetrance genes (ATM, CHEK2: 10–15% at 10 years). These data are directly usable for prophylactic contralateral mastectomy decisions during post-diagnostic genetics consultation.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Gene-specific CBC risk quantification is missing data in current practice: contralateral mastectomy decisions were previously guided by BRCA1/2 data and extrapolated to other genes. This meta-analysis fills this gap for PALB2, CHEK2, and ATM, enabling more precise genetic counseling on contralateral prophylactic surgery in intermediate-penetrance families.

Clinical impact: 3/3 · Evidence strength: 3/3 · Novelty: 1/2 · Sample size: 1/1 · Publication status: 1/1 → Total: 9/10