Martín, MiguelRodríguez-Lescure, ÁlvaroRuiz, AmparoAlba Conejo, EmilioCalvo, LourdesRuiz-Borrego, ManuelMuñárriz, BlancaRodríguez, César ACrespo, CarmenÁlava, Enrique deLópez García-Asenjo, José AntonioGuitián, María DoloresAlmenar, SergioGonzález-Palacios, Jesús FernandoVera, FranciscoPalacios, JoséRamos, ManuelGracia Marco, José ManuelLluch, AnaÁlvarez, IsabelSeguí, Miguel ÁngelMayordomo, José IgnacioAntón, AntonioBaena, José ManuelPlazaola, ArrateModolell, AlfonsoPelegrí, AmadeuMel, José RamónAranda, EnriqueAdrover, EncarnaValero Álvarez, JoséGarcía Puche, José LuisSánchez-Rovira, PedroGonzález, SoniaLópez-Vega, José Manuel2013-01-312013-01-312008-06-04Martín M, Rodríguez-Lescure A, Ruiz A, Alba E, Calvo L, Ruiz-Borrego M, et al. Randomized phase 3 trial of fluorouracil, epirubicin, and cyclophosphamide alone or followed by Paclitaxel for early breast cancer. J. Natl. Cancer Inst.. 2008 ; 100(11):805-140027-8874http://hdl.handle.net/10668/749Clinical Trial, Phase III; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't;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.enERBB2 protein, humanAncianoAntineoplásicos FitogénicosProtocolos de Quimioterapia Combinada AntineoplásicaNeoplasias de la MamaCarcinoma Ductal de MamaCarcinoma LobularCiclofosfamidaSupervivencia sin EnfermedadEsquema de MedicaciónEpirrubicinaFluorouraciloInmunohistoquímicaHibridación Fluorescente In SituInfusiones IntravenosasEstimación de Kaplan-MeierEstadificación de NeoplasiasPronósticoModelos de Riesgos ProporcionalesReceptor erbB-2Receptores EstrogénicosReceptores de ProgesteronaResultado del TratamientoMarcadores Biológicos de TumorMedical Subject Headings::Named Groups::Persons::Age Groups::Adult::AgedMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Therapeutic Uses::Antineoplastic Agents::Antineoplastic Agents, PhytogenicMedical Subject Headings::Analytical, 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Headings::Chemicals and Drugs::Biological Factors::Biological Markers::Tumor Markers, BiologicalMedical Subject Headings::Named Groups::Persons::Age Groups::Adultresearch article18505968open access10.1093/jnci/djn1511460-2105