title: Immunohistochemical subtypes predict the clinical outcome in high-risk node-negative breast cancer patients treated with adjuvant FEC regimen: results of a single-center retrospective study.
abstract: BACKGROUND
  Anthracycline-based adjuvant chemotherapy improves survival in patients with high-risk node-negative breast cancer (BC). In this setting, prognostic factors predicting for treatment failure might help selecting among the different available cytotoxic combinations.
  
  
  METHODS
  Between 1998 and 2008, 757 consecutive patients with node-negative BC treated in our institution with adjuvant FEC (5FU, epirubicin, cyclophosphamide) chemotherapy were identified. Data collection included demographic, clinico-pathological characteristics and treatment information. Molecular subtypes were derived from estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Scarff-Bloom-Richardson (SBR) grade. Disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were estimated using the Kaplan-Meier Method, and prognostic factors were examined by multivariate Cox analysis.
  
  
  RESULTS
  After a median follow-up of 70 months, the 5-year DFS, DDFS and OS were 90.6 % (95 % confidence interval (CI): 88.2-93.1), 92.8 % (95 % CI: 90.7-95) and 95.1 % (95 % CI, 93.3-96.9), respectively. In the multivariate analysis including classical clinico-pathological parameters, only grade 3 maintained a significant and independent adverse prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, only luminal B/HER2-negative and triple-negative subtypes were associated with reduced DFS and DDFS.
  
  
  CONCLUSIONS
  Node-negative BC patients receiving adjuvant FEC regimen have a favorable outcome. Luminal B/HER2-negative and triple-negative subtypes identify patients with a higher risk of treatment failure, which might warrant more aggressive systemic treatment.
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Bd. Sainte-Marguerite, 13009, Marseille, France. rahalsoraya@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Rahal
authors.affiliation: Department of Biostatistics, Institut Paoli-Calmettes, Marseille, France. boherjm@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. boherjm@ipc.unicancer.fr.
authors.forename: J M
authors.initials: JM
authors.lastname: Boher
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Bd. Sainte-Marguerite, 13009, Marseille, France. extrajm@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. extrajm@ipc.unicancer.fr.
authors.forename: J M
authors.initials: JM
authors.lastname: Extra
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Bd. Sainte-Marguerite, 13009, Marseille, France. tarpinc@ipc.unicancer.fr.
authors.forename: C
authors.initials: C
authors.lastname: Tarpin
authors.affiliation: Department of Biopathology, Institut Paoli-Calmettes, Marseille, France. jauffrete@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. jauffrete@ipc.unicancer.fr.|Aix-Marseille University, Marseille, France. jauffrete@ipc.unicancer.fr.
authors.forename: E
authors.initials: E
authors.lastname: Charafe-Jauffret
authors.affiliation: Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France. lambaudiee@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. lambaudiee@ipc.unicancer.fr.
authors.forename: E
authors.initials: E
authors.lastname: Lambaudie
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Bd. Sainte-Marguerite, 13009, Marseille, France. sabatierr@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. sabatierr@ipc.unicancer.fr.|Aix-Marseille University, Marseille, France. sabatierr@ipc.unicancer.fr.
authors.forename: R
authors.initials: R
authors.lastname: Sabatier
authors.affiliation: Department of Biopathology, Institut Paoli-Calmettes, Marseille, France. THOMASSINJ@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. THOMASSINJ@ipc.unicancer.fr.
authors.forename: J
authors.initials: J
authors.lastname: Thomassin-Piana
authors.affiliation: Department of Radiation Oncology, Institut Paoli-Calmettes, Marseille, France. TALLETA@ipc.unicancer.fr.
authors.forename: A
authors.initials: A
authors.lastname: Tallet
authors.affiliation: Department of Radiation Oncology, Institut Paoli-Calmettes, Marseille, France. resbeutm@ipc.unicancer.fr.
authors.forename: M
authors.initials: M
authors.lastname: Resbeut
authors.affiliation: Department of Surgical Oncology, Institut Paoli-Calmettes, Marseille, France. HOUVENAEGHELG@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. HOUVENAEGHELG@ipc.unicancer.fr.|Aix-Marseille University, Marseille, France. HOUVENAEGHELG@ipc.unicancer.fr.
authors.forename: G
authors.initials: G
authors.lastname: Houvenaeghel
authors.affiliation: Data Management and Analysis Center, Institut Paoli-Calmettes, Marseille, France. labordel@ipc.unicancer.fr.
authors.forename: L
authors.initials: L
authors.lastname: Laborde
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Bd. Sainte-Marguerite, 13009, Marseille, France. bertuccif@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. bertuccif@ipc.unicancer.fr.|Aix-Marseille University, Marseille, France. bertuccif@ipc.unicancer.fr.
authors.forename: F
authors.initials: F
authors.lastname: Bertucci
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Bd. Sainte-Marguerite, 13009, Marseille, France. viensp@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. viensp@ipc.unicancer.fr.|Aix-Marseille University, Marseille, France. viensp@ipc.unicancer.fr.
authors.forename: P
authors.initials: P
authors.lastname: Viens
authors.affiliation: Department of Medical Oncology, Institut Paoli-Calmettes, 232 Bd. Sainte-Marguerite, 13009, Marseille, France. goncalvesa@ipc.unicancer.fr.|Centre de Recherche en Cancérologie de Marseille, U1068 INSERM, U7258 CNRS, Marseille, France. goncalvesa@ipc.unicancer.fr.|Aix-Marseille University, Marseille, France. goncalvesa@ipc.unicancer.fr.
authors.forename: A
authors.initials: A
authors.lastname: Gonçalves
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use; D015251:Epirubicin / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D015251:Epirubicin; D003520:Cyclophosphamide; D005472:Fluorouracil