Effects of BRCA variation on prognosis in patients with nonmetastatic breast cancer

Ann Hum Genet. 2024 Nov;88(6):436-444. doi: 10.1111/ahg.12577. Epub 2024 Aug 29.

Abstract

Background: To compare the clinicopathological characteristics of nonmetastatic breast cancer patients with and without BRCA variations and to investigate the impact of BRCA variations on prognosis.

Methods: This retrospective single-center study involved an analysis of 938 patients with localized or locally advanced breast cancer who underwent BRCA variation testing. The patients were divided into three groups: 757 were without BRCA variation, 64 were with BRCA1 variation, and 117 were with BRCA2 variation.

Results: In patients with BRCA1 variation, the Ki67, grade, and frequency of triple-negative breast cancer were significantly higher than in patients without BRCA variation and with BRCA2 variation. The 5-year disease-free survival in patients with BRCA1 variation was significantly worse than the other two groups (without BRCA, BRCA1, and BRCA2; 87.7%, 69.9%, and 95.3%, respectively, p = 0.049). Multivariate analysis detected no significant difference between groups. The pathological complete response rates with neoadjuvant therapy were significantly better in patients with BRCA variations than those without BRCA variations (49.2% vs. 29.6%, p = 0.024).

Conclusion: Patients with BRCA1 variation had more aggressive tumor characteristics, such as higher Ki67 and higher grade. Also, triple-negative breast cancer was more common. The presence of BRCA1 variation may worsen survival outcomes. Neoadjuvant treatment responses of patients with BRCA variations were significantly better, and neoadjuvant treatment may contribute to survival outcomes in nonmetastatic patients with BRCA variations.

Keywords: BRCA variations; breast cancer; genetic; survival.

MeSH terms

  • Adult
  • Aged
  • BRCA1 Protein* / genetics
  • BRCA2 Protein* / genetics
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism
  • Middle Aged
  • Neoadjuvant Therapy
  • Prognosis
  • Retrospective Studies
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / pathology

Substances

  • BRCA1 Protein
  • BRCA2 Protein
  • BRCA1 protein, human
  • BRCA2 protein, human
  • Ki-67 Antigen