BRCA1/2 mutation carriers vs the general breast cancer population (N = 799,986): 21-gene assay-based molecular characterization

Breast Cancer Res Treat. 2024 Jul;206(1):67-76. doi: 10.1007/s10549-024-07271-4. Epub 2024 Apr 3.

Abstract

Purpose: We compared 21-gene recurrence score (RS) distribution and expression of the single-gene/gene groups within this assay between BC patients with pathogenic variants (PV) in BRCA1/2 vs the general 21-gene-tested BC population.

Methods: This retrospective study included consecutive 21-gene-tested female ER + HER2-negative BC patients with germline PVs in BRCA1/2. RS/gene expression data were compared to a previously described commercial use database (CDB, N = 799,986). Chi-square and 1-sample t test were used to compare RS distribution and single-gene/gene group scores between the study group and the CDB.

Results: Study group patients (N = 81) were younger and their RS results were higher compared to the CDB (age: median [IQR], 56 [47-61.5] vs 60 [51-67] years; p < 0.001; proportion of patients with RS ≥ 26: 49.4% vs 16.4%, p < 0.001). Expression of 12/16 cancer genes in the assay and the ER, proliferation, and invasion gene group scores differed significantly between the study group and the CDB, all in a direction contributing to higher RS. The differences between the study group and the CDB were mostly retained, upon stratifying the patients by menopausal status.

Conclusion: BC patients with PVs in BRCA1/2 have higher RS results that stem from distinct gene expression profiles in the majority of genes in the 21-gene assay.

Keywords: 21-gene assay; BRCA; Breast cancer; Clinical outcomes; Pathogenic variant; Recurrence Score.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein* / genetics
  • BRCA2 Protein* / genetics
  • Biomarkers, Tumor / genetics
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Female
  • Genetic Predisposition to Disease
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Middle Aged
  • Mutation
  • Retrospective Studies

Substances

  • BRCA2 Protein
  • BRCA1 Protein
  • BRCA1 protein, human
  • BRCA2 protein, human
  • Biomarkers, Tumor