title: Promoter methylation of BRCA1 in triple-negative breast cancer predicts sensitivity to adjuvant chemotherapy.
abstract: BACKGROUND
  BRCA1 function is inactivated through BRCA1 promoter methylation in a substantial number of triple-negative breast cancers. We investigated the impact of BRCA1-methylation status on the efficacy of adjuvant chemotherapy in patients with triple-negative breast cancer or with non-triple-negative breast cancer.
  
  
  METHODS
  BRCA1 promoter methylation was assessed in 1163 unselected breast cancer patients. Methylation was evaluated using a methylation-specific PCR (MSP) assay.
  
  
  RESULTS
  In the subgroup of 167 triple-negative breast cancer patients who received adjuvant chemotherapy, patients with BRCA1-methylated tumors had a superior 10-year disease-free survival (DFS)(78% versus 55%, P = 0.009) and 10-year disease-specific survival (DSS) (85% versus 69%, P = 0.024) than those with BRCA1-unmethylated tumors, and BRCA1 methylation was an independent favorable predictor of DFS and DSS in a multivariate analysis in this subgroup [DFS: hazard ratio (HR) = 0.45; 95% confidence interval (CI) 0.24-0.84; P = 0.019; DSS: HR = 0.43; 95% CI = 0.19-0.95; P = 0.044]. In contrast, in 675 non-triple-negative breast cancer patients who received adjuvant chemotherapy, BRCA1 methylation was an unfavorable predictor of DFS and DSS in univariate analysis (DFS: HR = 1.56; 95% CI 1.16-2.12; P = 0.003; DSS: HR = 1.53; 95% CI = 1.05-2.21; P = 0.026).
  
  
  CONCLUSIONS
  Triple-negative breast cancer patients with BRCA1-methylated tumors are sensitive to adjuvant chemotherapy and have a favorable survival compared with patients with BRCA1-unmethylated triple-negative tumors.
authors: Key Laboratory of Carcinogenesis and Translational Research, Ministry of Education, Breast Center, Peking University Cancer Hospital & Institute, Beijing, PR China.
authors: Y
authors: Y
authors: Xu
authors: L
authors: L
authors: Diao
authors: Y
authors: Y
authors: Chen
authors: Y
authors: Y
authors: Liu
authors: C
authors: C
authors: Wang
authors: T
authors: T
authors: Ouyang
authors: J
authors: J
authors: Li
authors: T
authors: T
authors: Wang
authors: Z
authors: Z
authors: Fan
authors: T
authors: T
authors: Fan
authors: B
authors: B
authors: Lin
authors: D
authors: D
authors: Deng
authors: S A
authors: SA
authors: Narod
authors: Y
authors: Y
authors: Xie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics* / Q000378:metabolism*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D019175:DNA Methylation / Q000235:genetics*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human
keywords: BRCA1 methylation; chemotherapy; triple-negative breast cancer