Gene expression profile and response to trastuzumab-docetaxel-based treatment in breast carcinoma

Br J Cancer. 2009 Oct 20;101(8):1357-64. doi: 10.1038/sj.bjc.6605310. Epub 2009 Sep 15.


Background: Resistance to trastuzumab is often observed in women with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and has been shown to involve multiple potential mechanisms. We examined the ability of microarray analyses to determine the potential markers of pathological complete response (pCR).

Methods: We conducted an analysis of tumours from 38 patients with locally advanced HER2-positive breast cancer who had received trastuzumab combined with docetaxel. Quantitative reverse transcriptase (RT)-PCR was used to assess the expression of 30 key genes; microarray analyses were carried out on 25 tumours to identify a prognostic gene expression profile, with 13 blinded samples used to validate the identified profile.

Results: No gene was found to correlate with response by RT-PCR. The microarray analysis identified a gene expression profile of 28 genes, with 12 upregulated in the pCR group and 16 upregulated in non-pCR. The leave-one-out cross-validation test exhibited 72% accuracy, 86% specificity, and 55% sensitivity. The 28-gene expression profile classified the 13 validation samples with 92% accuracy, 89% specificity, and 100% sensitivity.

Conclusion: Our results suggest that genes not involved in classical cancer pathways such as apoptosis or DNA repair could be involved in responses to a trastuzumab-docetaxel-based regimen. They also describe for the first time a gene expression signature that predicts trastuzumab response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Docetaxel
  • Female
  • Gene Expression Profiling*
  • Humans
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Receptor, ErbB-2 / analysis
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Taxoids / administration & dosage
  • Trastuzumab


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Taxoids
  • Docetaxel
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab