title: Gene expression signature predicting pathologic complete response with gemcitabine, epirubicin, and docetaxel in primary breast cancer.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  In conclusion, our gene expression signature allows prediction of pCR to PST containing G, E, and Doc with unprecedented high overall accuracy and robustness.
authors.affiliation: Division of Molecular Genetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Thuerigen
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.forename: Grischa
authors.initials: G
authors.lastname: Toedt
authors.forename: Patrick
authors.initials: P
authors.lastname: Warnat
authors.forename: Meinhard
authors.initials: M
authors.lastname: Hahn
authors.forename: Heidi
authors.initials: H
authors.lastname: Kramer
authors.forename: Benedikt
authors.initials: B
authors.lastname: Brors
authors.forename: Christian
authors.initials: C
authors.lastname: Rudlowski
authors.forename: Axel
authors.initials: A
authors.lastname: Benner
authors.forename: Florian
authors.initials: F
authors.lastname: Schuetz
authors.forename: Bjoern
authors.initials: B
authors.lastname: Tews
authors.forename: Roland
authors.initials: R
authors.lastname: Eils
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Sinn
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077143:Docetaxel; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D012680:Sensitivity and Specificity; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D043823:Taxoids; D003841:Deoxycytidine; D000077143:Docetaxel; D015251:Epirubicin; D000093542:Gemcitabine