BRCA1 promoter methylation is a marker of better response to anthracycline-based therapy in sporadic TNBC

Breast Cancer Res Treat. 2013 Sep;141(2):205-12. doi: 10.1007/s10549-013-2693-9. Epub 2013 Sep 13.

Abstract

The aim of the current study was to investigate the role of BRCA1 gene aberrations in sporadic triple-negative breast cancer (TNBC) and its impact on anthracycline-based therapy. BRCA1 promoter methylation was analyzed in 70 TNBC and compared with the clinical and pathologic characteristics. As a control group, we used 70 patients with non-TNBC. BRCA1 promoter methylation was observed in 65.2 % of patients and was similar in both groups. BRCA1 promoter methylation was associated with decreased intensity of BRCA1 protein expression (P = 0.002) and significant increase of median disease-free survival (DFS) of TNBC patients receiving adjuvant anthracycline-based chemotherapy (P = 0.001). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to DFS (HR 0.224; 95 % CI 0.092-0.546, P = 0.001) in TNBC after adjustment for other prognostic factors. In contrast, in non-TNBC, BRCA1 promoter methylation was not associated with any clinical and pathologic parameters. BRCA1 promoter methylation is a common mechanism of BRCA1 gene aberration in sporadic breast cancer and is predictive for better response to anthracycline-based therapies.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anthracyclines / therapeutic use
  • Antineoplastic Agents / therapeutic use
  • BRCA1 Protein / genetics*
  • BRCA1 Protein / metabolism
  • DNA Methylation*
  • Female
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Mutation
  • Neoplasm Grading
  • Prognosis
  • Promoter Regions, Genetic*
  • Treatment Outcome
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / mortality
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Burden

Substances

  • Anthracyclines
  • Antineoplastic Agents
  • BRCA1 Protein