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.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.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.In conclusion, our gene expression signature allows prediction of pCR to PST containing G, E, and Doc with unprecedented high overall accuracy and robustness.
%0 Journal Article
%1 thuerigen2006expression
%A Thuerigen, Olaf
%A Schneeweiss, Andreas
%A Toedt, Grischa
%A Warnat, Patrick
%A Hahn, Meinhard
%A Kramer, Heidi
%A Brors, Benedikt
%A Rudlowski, Christian
%A Benner, Axel
%A Schuetz, Florian
%A Tews, Bjoern
%A Eils, Roland
%A Sinn, Hans-Peter
%A Sohn, Christof
%A Lichter, Peter
%D 2006
%J J Clin Oncol
%K /&/ Adult; Aged; Algorithms; Analysis; Antineoplastic Breast Chemotherapy Combined Deoxycytidine, Epirubicin, Expression Female; Gene Humans; Immunohistochemistry; Middle Multivariate Neoplasms, Outcome Predictive Profiling; Protocols, Sensitivity Specificity; Taxoids, Tests; Treatment Value administration and derivatives; dosage/analogs dosage; drug of therapeutic therapy/genetics/pathology; use;
%N 12
%P 1839--1845
%R 10.1200/JCO.2005.04.7019
%T Gene expression signature predicting pathologic complete response with gemcitabine, epirubicin, and docetaxel in primary breast cancer.
%U http://dx.doi.org/10.1200/JCO.2005.04.7019
%V 24
%X 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.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.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.In conclusion, our gene expression signature allows prediction of pCR to PST containing G, E, and Doc with unprecedented high overall accuracy and robustness.
@article{thuerigen2006expression,
__markedentry = {[bbrors:6]},
abstract = {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.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.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.In conclusion, our gene expression signature allows prediction of pCR to PST containing G, E, and Doc with unprecedented high overall accuracy and robustness.},
added-at = {2015-04-09T12:36:21.000+0200},
author = {Thuerigen, Olaf and Schneeweiss, Andreas and Toedt, Grischa and Warnat, Patrick and Hahn, Meinhard and Kramer, Heidi and Brors, Benedikt and Rudlowski, Christian and Benner, Axel and Schuetz, Florian and Tews, Bjoern and Eils, Roland and Sinn, Hans-Peter and Sohn, Christof and Lichter, Peter},
biburl = {https://www.bibsonomy.org/bibtex/217947ce6ba3b882718c5a6703625c423/bbrors},
doi = {10.1200/JCO.2005.04.7019},
institution = {Division of Molecular Genetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany.},
interhash = {5345bd65c252f9f7d586bfff680ea7c3},
intrahash = {17947ce6ba3b882718c5a6703625c423},
journal = {J Clin Oncol},
keywords = {/&/ Adult; Aged; Algorithms; Analysis; Antineoplastic Breast Chemotherapy Combined Deoxycytidine, Epirubicin, Expression Female; Gene Humans; Immunohistochemistry; Middle Multivariate Neoplasms, Outcome Predictive Profiling; Protocols, Sensitivity Specificity; Taxoids, Tests; Treatment Value administration and derivatives; dosage/analogs dosage; drug of therapeutic therapy/genetics/pathology; use;},
language = {eng},
medline-pst = {ppublish},
month = Apr,
number = 12,
owner = {bbrors},
pages = {1839--1845},
pii = {24/12/1839},
pmid = {16622258},
timestamp = {2015-04-09T12:36:21.000+0200},
title = {Gene expression signature predicting pathologic complete response with gemcitabine, epirubicin, and docetaxel in primary breast cancer.},
url = {http://dx.doi.org/10.1200/JCO.2005.04.7019},
volume = 24,
year = 2006
}