title: A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer.
abstract: To better understand the relationship between tumor-host interactions and the efficacy of chemotherapy, we have developed an analytical approach to quantify several biological processes observed in gene expression data sets. We tested the approach on tumor biopsies from individuals with estrogen receptor-negative breast cancer treated with chemotherapy. We report that increased stromal gene expression predicts resistance to preoperative chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide (FEC) in subjects in the EORTC 10994/BIG 00-01 trial. The predictive value of the stromal signature was successfully validated in two independent cohorts of subjects who received chemotherapy but not in an untreated control group, indicating that the signature is predictive rather than prognostic. The genes in the signature are expressed in reactive stroma, according to reanalysis of data from microdissected breast tumor samples. These findings identify a previously undescribed resistance mechanism to FEC treatment and suggest that antistromal agents may offer new ways to overcome resistance to chemotherapy.
authors.affiliation: Swiss National Centre of Competence in Research Molecular Oncology, Swiss Institute for Experimental Cancer Research, Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, Epalinges s/Lausanne, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Farmer
authors.forename: Hervé
authors.initials: H
authors.lastname: Bonnefoi
authors.forename: Pascale
authors.initials: P
authors.lastname: Anderle
authors.forename: David
authors.initials: D
authors.lastname: Cameron
authors.forename: Pratyaksha
authors.initials: P
authors.lastname: Wirapati
authors.forename: Pratyakasha
authors.initials: P
authors.lastname: Wirapati
authors.forename: Véronique
authors.initials: V
authors.lastname: Becette
authors.forename: Sylvie
authors.initials: S
authors.lastname: André
authors.forename: Martine
authors.initials: M
authors.lastname: Piccart
authors.forename: Mario
authors.initials: M
authors.lastname: Campone
authors.forename: Etienne
authors.initials: E
authors.lastname: Brain
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Macgrogan
authors.forename: Thierry
authors.initials: T
authors.lastname: Petit
authors.forename: Jacek
authors.initials: J
authors.lastname: Jassem
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bibeau
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Blot
authors.forename: Jan
authors.initials: J
authors.lastname: Bogaerts
authors.forename: Michel
authors.initials: M
authors.lastname: Aguet
authors.forename: Jonas
authors.initials: J
authors.lastname: Bergh
authors.forename: Richard
authors.initials: R
authors.lastname: Iggo
authors.forename: Mauro
authors.initials: M
authors.lastname: Delorenzi
mesh_terms: D000465:Algorithms; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020360:Neoadjuvant Therapy; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes / Q000502:physiology; D011237:Predictive Value of Tests; D011379:Prognosis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology