Molecular predictors of efficacy of adjuvant weekly paclitaxel in early breast cancer

Abstract

Treatment with fluororacil, epirubicin, and cyclophosphamide followed by weekly paclitaxel (FEC-P) yielded superior disease-free survival than FEC in the adjuvant breast cancer trial GEICAM 9906. We evaluate molecular subtypes predictive of prognosis and paclitaxel response in this trial. Two molecular subtype classifications based on conventional immunohistochemical and fluorescent in situ hybridization determinations were used: #1: Four groups segregated according to the combination of hormone receptor (HR) and HER2 status; #2: Intrinsic subtype classification (Triple Negative (TN), HER2, Luminal B and Luminal A). Results: Both subtype classifications yielded prognostic and predictive information. HR +/HER2− patients (and Luminal A patients) had a significantly better outcome than the other subgroups of patients. The superiority of FEC-P over FEC was clearly more marked in HR−/HER2− patients (TN patients), particularly in the subset with basal phenotype (TN and either EGFR+ or cytokeratins 5/6+). The Luminal A subtype also achieved a significant benefit with FEC-P. The molecular-defined subgroup of TN was clearly predictive of better response to treatment with FEC-P. Luminal A patients had the best prognosis and also have a better outcome with weekly paclitaxel.

Appendix

The following investigators, with their affiliations, participated in the GEICAM 9906 trial:

Hospital General Universitario Gregorio Marañón, Madrid, Spain—M. Martín and J. A. LópezGarcía-Asenjo; Hospital Universitario de Elche, Elche, Spain—Á. Rodríguez-Lescure; Instituto Valenciano de Oncología, Valencia, Spain—A. Ruiz and S.Almenar; Hospital Virgen de la Victoria, Málaga, Spain—E. Alba and L. Vicioso;Complexo Hospitalario Universitario A Coruña, La Coruña, Spain—L. Calvo and M. D. Guitián; Hospital Vírgen del Rocío, Sevilla, Spain—M. Ruiz-Borrego and J. Palacios; Hospital La Fe, Valencia, Spain—B. Munárriz and F. Vera; Hospital Universitario de Salamanca, Salamanca, Spain—C. A. Rodríguez; Hospital Ramón y Cajal, Madrid, Spain—C. Crespo and J. F. González-Palacios; Centro Oncológico de Galicia, La Coruña, Spain—M. Ramos and A. de la Cruz; Hospital de Cabueñes, Gijón, Spain—J. M. Gracia and J. Martín; Hospital Clínico de Valencia, Valencia, Spain—A. Lluch and J. Ferrer; Hospital Donostia, San Sebastián, Spain—I. Álvarez and I. Ruiz; Hospital Parc Taulí, Sabadell, Spain—M. Á. Seguí and A. Sáez; Hospital Clínico Lozano Blesa, Zaragoza, Spain—J. I. Mayordomo and M. Moros; Hospital Miguel Servet, Zaragoza, Spain—A. Antón and M. José Ríos; Complejo Hospitalario Puerta del Mar, Cádiz, Spain—J. M. Baena and M. J. Palomo; Instituto Oncológico de Guipúzcoa, San Sebastián, Spain—A. Plazaola and R. Rezola; Clínica Corachan, Barcelona, Spain—A. Modolell and P. de las Heras; Hospital Universitario San Joan de Reus, Reus, Spain—A. Pelegrí and F. Riu; Complejo Hospitalario Xeral Calde, Lugo, Spain—J. R. Mel and J. Alba; Hospital Provincial de Córdoba, Córdoba, Spain—E. Aranda and E. Fuentes; Hospital General de Alicante, Alicante, Spain—E. Adrover and G. Peiró; Hospital Provincial de Zamora, Zamora, Spain—J. V. Álvarez and J. C. Solera; Hospital San Cecilio de Granada, Granada, Spain—J. L. G. Puche and J. Aneiros; Hospital Ciudad de Jaén, Jaén, Spain—P. Sánchez-Rovira and C. Cueva; Hospital Mutua de Terrasa, Terrasa, Spain—S. Gonzalez and A. Salas; Hospital Marqués de Valdecilla, Santander, Spain—J. M. López-Vega and M. Francisca Garijo; Hospital Txagorritxu, Vitoria, Spain—S. Domínguez and Mª. A. Viguri; Hospital Comarcal Barbastro, Barbastro, Spain—J. Florian and R. Oncins; Hospital Universitario De Canarias, Tenerife, Spain—N. Batista and R. Méndez; Hospital de Elda, Elda, Spain—C. Llorca and S. Alonso Hernández; Hospital General de Móstoles, Móstoles, Spain—M. Méndez and M. J. Mestre; Hospital Clínico Barcelona, Barcelona, Spain—M. Muñoz and P. Fernández; Hospital General Universitario de Valencia, Valencia, Spain—Mª. J. Godes and A. Pérez; Hospital General de Ciudad Real, Ciudad Real, Spain—M. J. García and M. Carbajo; Hospital Puerta de Hierro, Madrid, Spain—R. Cubedo and E. Tejerina; Althaia Xarxa Assistencial Manresa, Manresa, Spain—I. Guash and L. Sardans; Hospital General de Jerez, Jerez, Spain—A. Moreno and A. Rodríguez; Hospital Universitario Insular, Las Palmas, Spain—A. Murias and M. Pavcovich; Fundación Hospital de Alcorcón, Alcorcón, Spain—C. Jara and M.Argüelles; Hospital Juan Ramón Jiménez, Huelva, Spain—B. Calero and J.Conde; Hospital Arnau de Vilanova, Lérida, Spain—V. Alberola and J. Fernando;Hospital General Universitario de Guadalajara, Guadalajara, Spain—J. Casinello and J. Cuevas; Hospital Municipal de Badalona, Badalona, Spain—I. Moreno and M. Gómez; Hospital de Cruces, Barakaldo, Spain—J. R. Barceló and J. Mª Ribera; Hospital del Mar, Barcelona, Spain—I. Tusquets and J. Mª Corominas; Hospital de León, León, Spain—A. García and T. Arribas; Complejo Hospitalario de Orense, Orense, Spain—J. García and C. Peñin; Hospital Río Carrión, Palencia, Spain—A. Arizcum and L. Pérez; Hospital Universitario de Gran Canaria Doctor Negrín, Las Palmas, Spain—J. Aguiar and M. A. Limeres; Hospital Virgen de la Salud, Toledo, Spain—M. A. de la Cruz and J. Martín; Hospital de L′Esperit Sant, Santa Coloma de Gramenet, Spain—C. Martín and Mª A. Ruiz; Hospital de la Ribera, Valencia, J. Miguel and R. Cano; Hospital de Navarra, Pamplona, Spain; J. J. Valerdi and A. Córdoba; Hospital Universitario de Valladolid, Valladolid, Spain—F. López and I. Peral; Hospital Morales Messeguer, Murcia, Spain—F. Ayala and M. A. Chaves; Hospital Germans Trias y Pujol, Badalona, Spain—A. Barnadas and E. Castellá; Hospital Virgen de los Lírios, Alicante, Spain—A. Oltra and J. L. Losa; Hospital Universitario Puerto Real, Puerto Real, Spain—A. Lorenzo and A. Hens; Hospital Doctor Peset, Valencia, Spain—D. Almenar and J. Escandón; Hospital Consorci Sanitari Terrasa, Terrassa, Spain—A. Arcusa and I. Roig; Hospital Puerto de Sagunto, Valencia, Spain—A. Galán and B. Martínez; Hospital de la Arrixaca, Murcia, Spain—J. L. Alonso and J. Bermejo; Hospital Provincial de Toledo, Toledo, Spain—P. Puñal and C. Pérez.