A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer

被引：521

作者：

Farmer, Pierre ^{[1
,2
]}

Bonnefoi, Herve ^{[3
,4
,5
,6
,7
,8
]}

Anderle, Pascale ^{[1
,9
]}

Cameron, David ^{[10
]}

Wirapati, Pratyakasha ^{[2
]}

Becette, Veronique ^{[11
]}

Andre, Sylvie ^{[1
]}

Piccart, Martine ^{[12
]}

Campone, Mario ^{[13
]}

Brain, Etienne ^{[11
]}

MacGrogan, Gaetan ^{[3
,4
,5
]}

Petit, Thierry ^{[14
]}

Jassem, Jacek ^{[15
]}

Bibeau, Frederic ^{[16
]}

Blot, Emmanuel ^{[17
]}

Bogaerts, Jan ^{[8
]}

Aguet, Michel ^{[1
]}

Bergh, Jonas ^{[18
,19
]}

Iggo, Richard ^{[1
,3
,4
,5
,20
]}

Delorenzi, Mauro ^{[1
,2
]}

机构：

[1] Swiss Natl Ctr Competence Res Mol Oncol, Swiss Inst Expt Canc Res, Ecole Polytech Fed Lausanne, Sch Life Sci, Lausanne, Switzerland

[2] Swiss Inst Bioinformat, CH-1015 Lausanne, Switzerland

[3] Inst Bergonie, F-33076 Bordeaux, France

[4] Univ Bordeaux 2, Inst Natl Sante, F-33076 Bordeaux, France

[5] Univ Bordeaux 2, Rech Med Unit, U916, F-33076 Bordeaux, France

[6] Hop Univ Geneve, CH-1211 Geneva, Switzerland

[7] Swiss Grp Clin Canc Res, CH-3008 Bern, Switzerland

[8] EORTC, B-1200 Brussels, Belgium

[9] Oncol Inst So Switzerland, Expt Oncol Lab, CH-6500 Bellinzona, Switzerland

[10] Western Gen Hosp, Univ Dept Oncol, Anglocelt Cooperat Oncol Grp, Edinburgh EH4 2XU, Midlothian, Scotland

[11] Ctr Rene Huguenin, F-92210 St Cloud, France

[12] Inst Jules Bordet, B-1000 Brussels, Belgium

[13] Ctr Cancerol, Inst Canc Nantes Atlant, Ctr Lutte Canc Rene Gauducheau, Inst Natl Sante & Rech Med 892, F-44805 Nantes, Saint Herbalin, France

[14] Ctr Paul Strauss, F-67065 Strasbourg, France

[15] Med Univ, PL-80211 Gdansk, Poland

[16] Ctr Val Aurelle Paul Lamarque, F-34298 Montpellier 5, France

[17] Ctr Henri Becquerel, F-76038 Rouen, France

[18] Karolinska Inst, Swedish Breast Canc Grp, S-17176 Stockholm, Sweden

[19] Karolinska Univ Hosp, S-17176 Stockholm, Sweden

[20] Univ St Andrews, Bute Med Sch, St Andrews KY16 9TS, Fife, Scotland

来源：

NATURE MEDICINE | 2009年 / 15卷 / 01期

基金：

瑞典研究理事会; 瑞士国家科学基金会;

关键词：

PATHOLOGICAL COMPLETE RESPONSE; DRUG-RESISTANCE; PREOPERATIVE CHEMOTHERAPY; EXPRESSION SIGNATURE; MOLECULAR PORTRAITS; TUMORS; CELLS; CARCINOMAS; DOCETAXEL; PROGNOSIS;

D O I：

10.1038/nm.1908

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：68 / 74

页数：7

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