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J Clin Oncol. 2006 Apr 20;24(12):1839-45.

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

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1
Division of Molecular Genetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany.

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.

PMID:
16622258
DOI:
10.1200/JCO.2005.04.7019
[Indexed for MEDLINE]
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