Identification of SNPs associated with response of breast cancer patients to neoadjuvant chemotherapy in the EORTC-10994 randomized phase III trial

Pharmacogenomics J. 2015 Feb;15(1):63-8. doi: 10.1038/tpj.2014.24. Epub 2014 Jun 24.

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.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Female
  • Genetic Association Studies* / methods
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy / methods*
  • Polymorphism, Single Nucleotide / genetics*
  • Treatment Outcome