BRCA1 promoter methylation is a marker of better response to platinum-taxane-based therapy in sporadic epithelial ovarian cancer

J Cancer Res Clin Oncol. 2014 Sep;140(9):1457-63. doi: 10.1007/s00432-014-1704-5. Epub 2014 May 14.

Abstract

Background: The aim of the current study was to investigate the role of BRCA1 promoter methylation as predictive factor of response to platinum-taxane-based therapy in sporadic ovarian cancer.

Patients and methods: BRCA1 promoter methylation was analyzed in 42 sporadic epithelial ovarian cancers. The results were validated in a second cohort of 137 ovarian cancer patients.

Results: BRCA1 promoter methylation was observed in 35.7 % of patients in the first group and in 33.6 % in the second group. BRCA1 promoter methylation was associated with significant increase in median progression-free survival (PFS) of ovarian cancer patients receiving adjuvant platinum-taxane-based chemotherapy (P = 0.008). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to PFS (HR 0.52; 95 % CI 0.32-0.85, P = 0.009) after adjustment for other prognostic factors. Under the patients with recurrent disease, BRCA1 promoter methylation was associated with significant longer median PFS of 18.5 months in comparison with 12.8 months PFS for patients without BRCA1 promoter methylation.

Conclusions: BRCA1 promoter methylation is predictive for better response to platinum-taxane-based therapy in EOC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • BRCA1 Protein / genetics*
  • Biomarkers, Tumor / genetics*
  • Bridged-Ring Compounds / administration & dosage
  • Carcinoma, Ovarian Epithelial
  • Disease-Free Survival
  • Female
  • Humans
  • Methylation / drug effects
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / drug therapy*
  • Neoplasms, Glandular and Epithelial / genetics*
  • Organoplatinum Compounds / administration & dosage
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics*
  • Prognosis
  • Promoter Regions, Genetic / genetics*
  • Taxoids / administration & dosage
  • Young Adult

Substances

  • BRCA1 Protein
  • Biomarkers, Tumor
  • Bridged-Ring Compounds
  • Organoplatinum Compounds
  • Taxoids
  • taxane