Challenging single- and multi-probesets gene expression signatures of pathological complete response to neoadjuvant chemotherapy in breast cancer: experience of the REMAGUS 02 phase II trial

Breast. 2013 Dec;22(6):1052-9. doi: 10.1016/j.breast.2013.08.015. Epub 2013 Oct 2.

Abstract

This study was designed to identify predictive signatures of pathological complete response (pCR) in breast cancer treated by taxane-based regimen, using clinicopathological variables and transcriptomic data (Affymetrix Hgu133 Plus 2.0 devices). The REMAGUS 02 trial (n = 153,training set) and the publicly available M.D. Anderson data set (n = 133, validation set) were used. A re-sampling method was applied. All predictive models were defined using logistic regression and their classification performances were tested through Area Under the Curve (AUC) estimation. A stable set of 42 probesets (31 genes) differentiate pCR or no pCR samples. Single-or 2-probesets signatures, mainly related to ER pathway, were equally predictive of pCR with AUC greater then 0.80. Models including probesets associated with ESR1, MAPT, CA12 or PIGH presented good classification performances. When clinical variables were entered into the model, only CA12 and PIGH, remained informative (p = 0.05 and p = 0.005) showing that a combination of a few genes provided robust and reliable prediction of pCR.

Keywords: Breast cancer; Neoadjuvant setting; Pathological complete response; Prediction; Transcriptome.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Bridged-Ring Compounds / administration & dosage
  • Carbonic Anhydrases / genetics
  • Chemotherapy, Adjuvant
  • Estrogen Receptor alpha / genetics
  • Female
  • Humans
  • Membrane Proteins / genetics
  • Middle Aged
  • Neoadjuvant Therapy
  • Oligonucleotide Array Sequence Analysis
  • Predictive Value of Tests
  • RNA / analysis
  • Receptors, Estrogen / analysis
  • Taxoids / administration & dosage
  • Transcriptome*
  • Treatment Outcome
  • tau Proteins / genetics

Substances

  • Biomarkers, Tumor
  • Bridged-Ring Compounds
  • ESR1 protein, human
  • Estrogen Receptor alpha
  • MAPT protein, human
  • Membrane Proteins
  • PIGH protein, human
  • Receptors, Estrogen
  • Taxoids
  • tau Proteins
  • taxane
  • RNA
  • Carbonic Anhydrases
  • carbonic anhydrase XII