title: ERCC1 polymorphisms as prognostic markers in T4 breast cancer patients treated with platinum-based chemotherapy.
abstract: BACKGROUND
  Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1) gene have been involved in the prognosis of various cancers. In the present study, we evaluated the prognostic role of the two most common ERCC1 polymorphisms in patients with T4 breast cancer receiving platinum-based chemotherapy.
  
  
  METHODS
  A total of 47 patients with T4 breast cancer undergoing treatment with a platinum-based regimen were collected and followed up (median 159 months; range, 42-239 months). ERCC1 C8092A (rs3212986) and T19007C (rs11615) polymorphisms were genotyped, using an automated sequencing approach. The same series was screened for BRCA1/2 mutations by DHPLC analysis and DNA sequencing.
  
  
  RESULTS
  Among the tested patients, 16 (34%) and 25 (53%) presented the 8092A (homo-zygosity A/A or heterozygosity A/C) and the 19007C (homozygosity C/C or heterozygosity C/T) genotypes, respectively. The 8092A and 19007C genotypes in ERCC1 were significantly associated with overall survival in T4 breast cancer patients treated with chemotherapy containing platinum (p-values = 0.036 and 0.004, respectively). Univariate and multivariate Cox regression analyses showed that combination of 8092A and 19007C genotypes acts as a significant prognostic factor in women with T4 breast cancer receiving platinum-based chemotherapy (p-values = 0.022 and 0.049, respectively). Two (4.3%) out of 47 cases were found to carry BRCA1/2 mutations; they presented the highest overall survival rates into the series.
  
  
  CONCLUSIONS
  The ERCC1 8092A and 19007C genotypes or their combination may predict a favorable prognosis in T4 breast cancer patients undergoing a platinum-based treatment. Further large-scale, prospective studies are needed to validate our findings.
authors.forename: Grazia
authors.initials: G
authors.lastname: Palomba
authors.forename: Francesco
authors.initials: F
authors.lastname: Atzori
authors.forename: Mario
authors.initials: M
authors.lastname: Budroni
authors.forename: MariaNeve
authors.initials: M
authors.lastname: Ombra
authors.forename: Antonio
authors.initials: A
authors.lastname: Cossu
authors.forename: MariaCristina
authors.initials: M
authors.lastname: Sini
authors.forename: Valeria
authors.initials: V
authors.lastname: Pusceddu
authors.forename: Bruno
authors.initials: B
authors.lastname: Massidda
authors.forename: Barbara
authors.initials: B
authors.lastname: Frau
authors.forename: Francesca
authors.initials: F
authors.lastname: Notari
authors.forename: MariaTeresa
authors.initials: M
authors.lastname: Ionta
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palmieri
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics; D002945:Cisplatin / Q000008:administration & dosage*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin