A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer.
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.
Farmer
Pierre
P
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.
Bonnefoi
Hervé
H
Anderle
Pascale
P
Cameron
David
D
Wirapati
Pratyaksha
P
Wirapati
Pratyakasha
P
Becette
Véronique
V
André
Sylvie
S
Piccart
Martine
M
Campone
Mario
M
Brain
Etienne
E
Macgrogan
Gaëtan
G
Petit
Thierry
T
Jassem
Jacek
J
Bibeau
Frédéric
F
Blot
Emmanuel
E
Bogaerts
Jan
J
Aguet
Michel
M
Bergh
Jonas
J
Iggo
Richard
R
Delorenzi
Mauro
M
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