This Article Full Text Full Text (PDF) Supplementary Data Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thuerigen, O. Articles by Lichter, P. Search for Related Content PubMed PubMed Citation Articles by Thuerigen, O. Articles by Lichter, P. Social Bookmarking                            What's this?

Gene Expression Signature Predicting Pathologic Complete Response With Gemcitabine, Epirubicin, and Docetaxel in Primary Breast Cancer

Olaf Thuerigen, Andreas Schneeweiss, Grischa Toedt, Patrick Warnat, Meinhard Hahn, Heidi Kramer, Benedikt Brors, Christian Rudlowski, Axel Benner, Florian Schuetz, Bjoern Tews, Roland Eils, Hans-Peter Sinn, Christof Sohn, Peter Lichter

From the Divisions of Molecular Genetics, Theoretical Bioinformatics, and Biostatistics, Deutsches Krebsforschungszentrum; and Departments of Gynecology and Obstetrics and Pathology, University of Heidelberg, Heidelberg, Germany

Address reprint requests to Andreas Schneeweiss, MD, Department of Gynecology and Obstetrics, University of Heidelberg, Hospitalstrasse, D-69115 Heidelberg, Germany; e-mail: andreas.schneeweiss{at}med.uni-heidelberg.de

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.

Supported by Research Fund from Lilly Deutschland GmbH.

Both O.T. and A.S. contributed equally to this study.

Presented in part at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				P. VICI, F. GIOTTA, L. DI LAURO, M. BRANDI, V. GEBBIA, P. FOGGI, V. LORUSSO, C. VITUCCI, D. SERGI, S. I. FATTORUSO, et al. Multicenter Phase II Trial of First-line Docetaxel/Gemcitabine in Advanced Breast Cancer Pretreated with Adjuvant Anthracyclines Anticancer Res, May 1, 2009; 29(5): 1841 - 1845. [Abstract] [Full Text] [PDF]

				L. Li, B. Fridley, K. Kalari, G. Jenkins, A. Batzler, S. Safgren, M. Hildebrandt, M. Ames, D. Schaid, and L. Wang Gemcitabine and Cytosine Arabinoside Cytotoxicity: Association with Lymphoblastoid Cell Expression Cancer Res., September 1, 2008; 68(17): 7050 - 7058. [Abstract] [Full Text] [PDF]

				P. Lonning, S Knappskog, V Staalesen, R Chrisanthar, and J. Lillehaug Breast cancer prognostication and prediction in the postgenomic era Ann. Onc., August 1, 2007; 18(8): 1293 - 1306. [Abstract] [Full Text] [PDF]

				F. Peintinger, K. Anderson, C. Mazouni, H. M. Kuerer, C. Hatzis, F. Lin, G. N. Hortobagyi, W. F. Symmans, and L. Pusztai Thirty-Gene Pharmacogenomic Test Correlates with Residual Cancer Burden after Preoperative Chemotherapy for Breast Cancer Clin. Cancer Res., July 15, 2007; 13(14): 4078 - 4082. [Abstract] [Full Text] [PDF]