Gene expression signature predicting pathologic complete response with gemcitabine, epirubicin, and docetaxel in primary breast cancer

J Clin Oncol. 2006 Apr 20;24(12):1839-45. doi: 10.1200/JCO.2005.04.7019.

Abstract

Purpose: Primary systemic therapy (PST) with gemcitabine (G), epirubicin (E), and docetaxel (Doc) has resulted in a pathologic complete response (pCR) in 26% of primary breast cancer patients. This study was aimed at the identification of a gene expression signature in diagnostic core biopsy tissue samples that predicts pCR.

Patients and methods: Core biopsy samples from patients with operable primary breast cancer, T2-4N0-2M0, enrolled onto two phase I and II trials evaluating GEDoc (n = 48) and GE sequentially followed by Doc (GEsDoc; n = 52) as PST were snap frozen and subjected to RNA expression profiling. A signature predicting pCR was discovered in the training set (GEsDoc) applying a support vector machine algorithm, and performance of this classifier was validated on the independent test set (GEDoc) by receiver operator characteristics analysis.

Results: We identified a signature consisting of 512 genes, which was enriched in genes involved in transforming growth factor beta and RAS-mediated signaling pathways, that predicts pCR with a sensitivity of 78%, a specificity of 90%, and an overall accuracy of 88% (95% CI, 75% to 95%). Apart from our signature, only HER2 overexpression was an independent predictor of pCR in multivariate analysis.

Conclusion: In conclusion, our gene expression signature allows prediction of pCR to PST containing G, E, and Doc with unprecedented high overall accuracy and robustness.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Docetaxel
  • Epirubicin / administration & dosage
  • Female
  • Gene Expression Profiling*
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Sensitivity and Specificity
  • Taxoids / administration & dosage
  • Treatment Outcome

Substances

  • Taxoids
  • Deoxycytidine
  • Docetaxel
  • Epirubicin
  • gemcitabine