Gene expression profile predicts outcome after anthracycline-based adjuvant chemotherapy in early breast cancer.
Prognosis of early beast cancer is heterogeneous. Today, no histoclinical or biological factor predictive for clinical outcome after adjuvant anthracycline-based chemotherapy (CT) has been validated and introduced in routine use. Using DNA microarrays, we searched for a gene expression signature associated with metastatic relapse after adjuvant anthracycline-based CT without taxane. We profiled a multicentric series of 595 breast cancers including 498 treated with such adjuvant CT. The identification of the prognostic signature was done using a metagene-based supervised approach in a learning set of 323 patients. The signature was then tested on an independent validation set comprising 175 similarly treated patients, 128 of them from the PACS01 prospective clinical trial. We identified a 3-metagene predictor of metastatic relapse in the learning set, and confirmed its independent prognostic impact in the validation set. In multivariate analysis, the predictor outperformed the individual current prognostic factors, as well as the Nottingham Prognostic Index-based classifier, both in the learning and the validation sets, and added independent prognostic information. Among the patients treated with adjuvant anthracycline-based CT, with a median follow-up of 68 months, the 5-year metastasis-free survival was 82% in the "good-prognosis" group and 56% in the "poor-prognosis" group. Our predictor refines the prediction of metastasis-free survival after adjuvant anthracycline-based CT and might help tailoring adjuvant CT regimens.
Bertucci
François
F
Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, Institut Paoli-Calmettes (IPC), Marseille, France. bertuccif@marseille.fnclcc.fr
Borie
Nathalie
N
Roche
Henri
H
Bachelot
Thomas
T
Le Doussal
Jean-Marc
JM
Macgrogan
Gaëtan
G
Debono
Stéphane
S
Martinec
Agnès
A
Treilleux
Isabelle
I
Finetti
Pascal
P
Esterni
Benjamin
B
Extra
Jean-Marc
JM
Geneve
Jean
J
Hermitte
Fabienne
F
Chabannon
Christian
C
Jacquemier
Jocelyne
J
Martin
Anne-Laure
AL
Longy
Michel
M
Maraninchi
Dominique
D
Fert
Vincent
V
Birnbaum
Daniel
D
Viens
Patrice
P
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D016896:Treatment Outcome
D018943:Anthracyclines; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor