title: Gene expression profile predicts outcome after anthracycline-based adjuvant chemotherapy in early breast cancer.
abstract: 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.
authors.affiliation: Département d'Oncologie Moléculaire, Centre de Recherche en Cancérologie de Marseille, UMR891 Inserm, Institut Paoli-Calmettes (IPC), Marseille, France. bertuccif@marseille.fnclcc.fr
authors.forename: François
authors.initials: F
authors.lastname: Bertucci
authors.forename: Nathalie
authors.initials: N
authors.lastname: Borie
authors.forename: Henri
authors.initials: H
authors.lastname: Roche
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Le Doussal
authors.forename: Gaëtan
authors.initials: G
authors.lastname: Macgrogan
authors.forename: Stéphane
authors.initials: S
authors.lastname: Debono
authors.forename: Agnès
authors.initials: A
authors.lastname: Martinec
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.forename: Pascal
authors.initials: P
authors.lastname: Finetti
authors.forename: Benjamin
authors.initials: B
authors.lastname: Esterni
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Extra
authors.forename: Jean
authors.initials: J
authors.lastname: Geneve
authors.forename: Fabienne
authors.initials: F
authors.lastname: Hermitte
authors.forename: Christian
authors.initials: C
authors.lastname: Chabannon
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Jacquemier
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Martin
authors.forename: Michel
authors.initials: M
authors.lastname: Longy
authors.forename: Dominique
authors.initials: D
authors.lastname: Maraninchi
authors.forename: Vincent
authors.initials: V
authors.lastname: Fert
authors.forename: Daniel
authors.initials: D
authors.lastname: Birnbaum
authors.forename: Patrice
authors.initials: P
authors.lastname: Viens
mesh_terms: 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
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor