title: Identification of SNPs associated with response of breast cancer patients to neoadjuvant chemotherapy in the EORTC-10994 randomized phase III trial.
abstract: Using cell line panels we identified associations between single-nucleotide polymorphisms (SNPs) and chemosensitivity. To validate these findings in clinics, we genotyped a subset of patients included in a neoadjuvant breast cancer trial to explore the relationship between genotypes and clinical outcome according to treatment received and p53 status. We genotyped 384 selected SNPs in the germline DNA extracted from formalin-fixed paraffin-embedded non-invaded lymph nodes of 243 patients. The polymorphisms of five selected genes were first studied, and then all 384 SNPs were considered. Correction for multiple testing was applied. CYP1B1 polymorphism was significantly associated with pathological complete response (pCR) in patients who had received DNA-damaging agents. MDM2, MDM4 and TP53BP1 polymorphisms were significantly associated with pCR in patients harboring a p53-positive tumor. In the complete SNP panel, there was a significant association between overall survival (OS) and a SNP of ADH1C, R272Q (P=0.0023). By multivariate analysis, only ADH1C genotype and p53 status were significantly associated with OS.
authors: INSERM U916, Institut Bergonié, Université Bordeaux Segalen, Bordeaux, France.
authors: V
authors: V
authors: Le Morvan
authors: European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.
authors: S
authors: S
authors: Litière
authors: INSERM U916, Institut Bergonié, Université Bordeaux Segalen, Bordeaux, France.
authors: A
authors: A
authors: Laroche-Clary
authors: INSERM U916, Institut Bergonié, Université Bordeaux Segalen, Bordeaux, France.
authors: S
authors: S
authors: Ait-Ouferoukh
authors: INSERM U916, Institut Bergonié, Université Bordeaux Segalen, Bordeaux, France.
authors: R
authors: R
authors: Bellott
authors: European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.
authors: C
authors: C
authors: Messina
authors: Edinburgh University, Edinburgh, UK.
authors: D
authors: D
authors: Cameron
authors: INSERM U916, Institut Bergonié, Université Bordeaux Segalen, Bordeaux, France.
authors: H
authors: H
authors: Bonnefoi
authors: INSERM U916, Institut Bergonié, Université Bordeaux Segalen, Bordeaux, France.
authors: J
authors: J
authors: Robert
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D016896:Treatment Outcome