title: Cell line derived multi-gene predictor of pathologic response to neoadjuvant chemotherapy in breast cancer: a validation study on US Oncology 02-103 clinical trial.
abstract: BACKGROUND
  The purpose of this study is to assess the predictive accuracy of a multi-gene predictor of response to docetaxel, 5-fluorouracil, epirubicin and cyclophosphamide combination chemotherapy on gene expression data from patients who received these drugs as neoadjuvant treatment.
  
  
  METHODS
  Tumor samples were obtained from patients with stage II-III breast cancer before starting neoadjuvant chemotherapy with four cycles of 5-fluorouracil/epirubicin/cyclophosphamide (FEC) followed by four cycles of docetaxel/capecitabine (TX) on US Oncology clinical trial 02-103. Most patients with HER-2-positive cancer also received trastuzumab (H). The chemotherapy predictor (TFEC-MGP) was developed from publicly available gene expression data of 42 breast cancer cell-lines with corresponding in vitro chemotherapy sensitivity results for the four chemotherapy drugs. No predictor was developed for treatment with trastuzumab. The predictive performance of TFEC-MGP in distinguishing cases with pathologic complete response from those with residual disease was evaluated for the FEC/TX and FEC/TX plus H group separately. The area under the receiver-operating characteristic curve (AU-ROC) was used as the metric of predictive performance. Genomic predictions were performed blinded to clinical outcome.
  
  
  RESULTS
  The AU-ROC was 0.70 (95% CI: 0.57-0.82) for the FEC/TX group (n=66) and 0.43 (95% CI: 0.20-0.66) for the FEC/TX plus H group (n=25). Among the patients treated with FEC/TX, the AU-ROC was 0.69 (95% CI: 0.52-0.86) for estrogen receptor (ER)-negative (n=28) and it was 0.59 (95% CI: 0.36-0.82) for ER-positive cancers (n=37). ER status was not reported for one patient.
  
  
  CONCLUSIONS
  Our results indicate that the cell line derived 291-probeset genomic predictor of response to FEC/TX combination chemotherapy shows good performance in a blinded validation study, particularly in ER-negative patients.
authors.affiliation: Department of Product Development, Precision Therapeutics, Inc, 2516 Jane Street, Pittsburgh, PA 15203, USA.
authors.forename: Kui
authors.initials: K
authors.lastname: Shen
authors.forename: Yuan
authors.initials: Y
authors.lastname: Qi
authors.forename: Nan
authors.initials: N
authors.lastname: Song
authors.forename: Chunqiao
authors.initials: C
authors.lastname: Tian
authors.forename: Shara D
authors.initials: SD
authors.lastname: Rice
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Gabrin
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Brower
authors.forename: William Fraser
authors.initials: WF
authors.lastname: Symmans
authors.forename: Joyce A
authors.initials: JA
authors.lastname: O'Shaughnessy
authors.forename: Frankie A
authors.initials: FA
authors.lastname: Holmes
authors.forename: Lina
authors.initials: L
authors.lastname: Asmar
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D019540:Area Under Curve; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002986:Clinical Trials as Topic; D003710:Demography; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D015203:Reproducibility of Results; D016896:Treatment Outcome; D014481:United States
chemical_list: D000970:Antineoplastic Agents