title: Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer.
abstract: BACKGROUND
  Taxanes are among the most active drugs for the treatment of metastatic breast cancer, and, as a consequence, they have also been studied in the adjuvant setting.
  
  
  METHODS
  After breast cancer surgery, women with lymph node-positive disease were randomly assigned to treatment with fluorouracil, epirubicin, and cyclophosphamide (FEC) or with FEC followed by weekly paclitaxel (FEC-P). The primary endpoint of study-5-year disease-free survival (DFS)-was assessed by Kaplan-Meier analysis. Secondary endpoints included overall survival and analysis of the prognostic and predictive value of clinical and molecular (hormone receptors by immunohistochemistry and HER2 by fluorescence in situ hybridization) markers. Associations and interactions were assessed with a multivariable Cox proportional hazards model for DFS for the following covariates: age, menopausal status, tumor size, lymph node status, type of chemotherapy, tumor size, positive lymph nodes, HER2 status, and hormone receptor status. All statistical tests were two-sided.
  
  
  RESULTS
  Among the 1246 eligible patients, estimated rates of DFS at 5 years were 78.5% in the FEC-P arm and 72.1% in the FEC arm (difference = 6.4%, 95% confidence interval [CI] = 1.6% to 11.2%; P = .006). FEC-P treatment was associated with a 23% reduction in the risk of relapse compared with FEC treatment (146 relapses in the 614 patients in the FEC-P arm vs 193 relapses in the 632 patients in the FEC arm, hazard ratio [HR] = 0.77, 95% CI = 0.62 to 0.95; P = .022) and a 22% reduction in the risk of death (73 and 95 deaths, respectively, HR = 0.78, 95% CI = 0.57 to 1.06; P = .110). Among the 928 patients for whom tumor samples were centrally analyzed, type of chemotherapy (FEC vs FEC-P) (P = .017), number of involved axillary lymph nodes (P < .001), tumor size (P = .020), hormone receptor status (P = .004), and HER2 status (P = .006) were all associated with DFS. We found no statistically significant interaction between HER2 status and paclitaxel treatment or between hormone receptor status and paclitaxel treatment.
  
  
  CONCLUSIONS
  Among patients with operable breast cancer, FEC-P treatment statistically significantly reduced the risk of relapse compared with FEC as adjuvant therapy.
authors.affiliation: Servicio de Oncologia Medica, Hospital Universitario San Carlos, Ciudad Universitaria s/n, 28040 Madrid, Spain. mmartin@geicam.org
authors.forename: Miguel
authors.initials: M
authors.lastname: Martín
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rodríguez-Lescure
authors.forename: Amparo
authors.initials: A
authors.lastname: Ruiz
authors.forename: Emilio
authors.initials: E
authors.lastname: Alba
authors.forename: Lourdes
authors.initials: L
authors.lastname: Calvo
authors.forename: Manuel
authors.initials: M
authors.lastname: Ruiz-Borrego
authors.forename: Blanca
authors.initials: B
authors.lastname: Munárriz
authors.forename: César A
authors.initials: CA
authors.lastname: Rodríguez
authors.forename: Carmen
authors.initials: C
authors.lastname: Crespo
authors.forename: Enrique
authors.initials: E
authors.lastname: de Alava
authors.forename: José Antonio
authors.initials: JA
authors.lastname: López García-Asenjo
authors.forename: María Dolores
authors.initials: MD
authors.lastname: Guitián
authors.forename: Sergio
authors.initials: S
authors.lastname: Almenar
authors.forename: Jesús Fernando
authors.initials: JF
authors.lastname: González-Palacios
authors.forename: Francisco
authors.initials: F
authors.lastname: Vera
authors.forename: José
authors.initials: J
authors.lastname: Palacios
authors.forename: Manuel
authors.initials: M
authors.lastname: Ramos
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Gracia Marco
authors.forename: Ana
authors.initials: A
authors.lastname: Lluch
authors.forename: Isabel
authors.initials: I
authors.lastname: Alvarez
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Seguí
authors.forename: José Ignacio
authors.initials: JI
authors.lastname: Mayordomo
authors.forename: Antonio
authors.initials: A
authors.lastname: Antón
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Baena
authors.forename: Arrate
authors.initials: A
authors.lastname: Plazaola
authors.forename: Alfonso
authors.initials: A
authors.lastname: Modolell
authors.forename: Amadeu
authors.initials: A
authors.lastname: Pelegrí
authors.forename: Jose Ramón
authors.initials: JR
authors.lastname: Mel
authors.forename: Enrique
authors.initials: E
authors.lastname: Aranda
authors.forename: Encarna
authors.initials: E
authors.lastname: Adrover
authors.forename: José Valero
authors.initials: JV
authors.lastname: Alvarez
authors.forename: José Luis
authors.initials: JL
authors.lastname: García Puche
authors.forename: Pedro
authors.initials: P
authors.lastname: Sánchez-Rovira
authors.forename: Sonia
authors.initials: S
authors.lastname: Gonzalez
authors.forename: José Manuel
authors.initials: JM
authors.lastname: López-Vega
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000556:secondary; D003520:Cyclophosphamide / Q000008:administration & dosage; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D015251:Epirubicin; D005472:Fluorouracil; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C508053:ERBB2 protein, human