TNBC: what mutated genes carry high risk?

  • J Natl Cancer Inst

  • de Miriam Davis, PhD
  • Résumé d’articles
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Takeaway

  • Mutations in BARD1, BRCA1, BRCA2, PALB2, and RAD51D genes are associated with high risk for triple-negative breast cancer (TNBC).

Why this matters

  • Patients with high-risk mutations may benefit from improved screening, risk management, and cancer prevention.

Study design

  • Case-control study of 10,901 patients with TNBC vs 26,000 population controls without TNBC.
  • Patients with TNBC were from 2 cohorts: 8753 patients with TNBC from a clinical cohort studied by multigene panel testing for 21 genes, and 2148 patients with TNBC from a research cohort (Triple Negative Breast Cancer Consortium) studied by multigene panel testing for 17 genes.
  • Funding: NIH; Breast Cancer Research Foundation.

Key results

  • High-risk germline pathogenic variants (ORs >5.0) were found in these genes in Caucasian patients (vs control patients): BARD1, BRCA1, BRCA2, PALB2, and RAD51D
  • These pathogenic variants were also associated with >20% lifetime risk for breast cancer of all types.
  • Moderate-risk germline pathogenic variants (ORs >2 but less than 5.0) were found in these genes in Caucasian patients (vs control patients): BRIP1, RAD51C, and TP53.
  • African American patients displayed similar patterns.

Limitations

  • Larger case-control studies and family-based segregation studies are warranted to refine risks.
  • Lack of study-level matching of patients with TNBC and control patients.