Pierre Kerbrat1, Isabelle Desmoulins2, Lise Roca3, Christelle Levy4, Alain Lortholary5, Alain Marre6, Rémy Delva7, Maria Rios8, Patrice Viens9, Étienne Brain10, Daniel Serin11, Magali Edel12, Marc Debled13, Mario Campone14, Marie-Ange Mourret-Reynier15, Thomas Bachelot16, Marie-Josèphe Foucher-Goudier17, Bernard Asselain18, Jérôme Lemonnier19, Anne-Laure Martin20, Henri Roché21. 1. Centre Eugène Marquis, Rue de la Bataille Flandres-Dunkerque - CS 44229, 35042 Rennes Cedex, France. Electronic address: p.kerbrat@rennes.unicancer.fr. 2. Centre Georges-François Leclerc, 1 rue Professeur Marion BP 77990, 21079 Dijon, France. Electronic address: Idesmoulins@cgfl.fr. 3. Institut régional du cancer de Montpellier, Parc Euromédecine, 208, rue des Apothicaires, 34298 Montpellier Cedex 5, France. Electronic address: Lise.Roca@icm.unicancer.fr. 4. Centre François Baclesse, 3 av du Général Harris, 14000 Caen, France. Electronic address: C.LEVY@baclesse.unicancer.fr. 5. Centre Catherine de Sienne, 2 rue Eric Tabarly, 44202 Nantes, France. Electronic address: Lortholary.alain@catherinedesienne.fr. 6. Centre Hospitalier, Avenue de l'Hopital, 12000 Rodez, France. Electronic address: a.marre@ch-rodez.fr. 7. Centre Paul Papin, 15 rue André Boquel, 49000 Angers, France. Electronic address: Franceremy.delva@ico.unicancer.fr. 8. Centre Alexis Vautrin, 6 avenue de Bourgogne, 54419 Vandoeuvre-Lès-Nancy, France. Electronic address: Francem.rios@nancy.unicancer.fr. 9. Institut Paoli-Calmettes, 232 Boulevard de Sainte-Marguerite, 13009 Marseille, France. Electronic address: Franceviensp@ipc.unicancer.fr. 10. Institut Curie, Site de Saint-Cloud, 35 rue Dailly, 92210 Saint-Cloud, France. Electronic address: etienne.brain@curie.fr. 11. Institut Sainte-Catherine, 250 Chemin de Baigne Pieds, 84918 Avignon, France. Electronic address: d.serin@isc84.org. 12. Centre hospitalier Émile Müller, 20 rue du Docteur Laennec, 68051 Mulhouse, France. Electronic address: edelm@ch-mulhouse.fr. 13. Institut Bergonié, 229 Cours de l'Argonne, 33000 Bordeaux, France. Electronic address: FranceM.Debled@bordeaux.unicancer.fr. 14. Institut de cancérologie de l'ouest, Centre René Gauducheau, Boulevard Professeur Jacques Monod, 44805 Saint-Herblain, France. Electronic address: FranceMario.Campone@ico.unicancer.fr. 15. Centre Jean Perrin, 58 rue Montalembert, 63000 Clermont-Ferrand, France. Electronic address: marie-ange.mouret-reynier@cjp.fr. 16. Centre Léon Bérard, 28 prom. Léa et Napoléon Bullukian, 69008 Lyon, France. Electronic address: thomas.bachelot@lyon.unicancer.fr. 17. Centre hospitalier Bretagne-Sud, 5 avenue de Choiseul, 56322 Lorient, France. Electronic address: mj.goudier@ch-bretagne-sud.fr. 18. Institut Curie, 26 rue d'Ulm, 75005 Paris, France. Electronic address: b.asselain@gmail.com. 19. R&D Unicancer, UCGB, 101 rue de Tolbiac, 75013 Paris, France. Electronic address: j-lemonnier@unicancer.fr. 20. R&D Unicancer, UCGB, 101 rue de Tolbiac, 75013 Paris, France. Electronic address: al-martin@unicancer.fr. 21. Institut Claudius Regaud, Institut Universitaire Cancer Toulouse-Oncopole, 1 avenue Irèle joliot-Curie, 31059 Toulouse Cedex 9, France. Electronic address: Roche.Henri@iuct-oncopole.fr.
Abstract
PURPOSE: Optimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial. PATIENTS AND METHODS: Between 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(-) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER- and PR-), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years. RESULTS: At 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% [0.89-1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91-2.13], P = .12). CONCLUSION: Differences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients. CLINICAL TRIAL REGISTRY NUMBER: NCT00055679, Agence National de Sécurité du Médicament (ANSM) - France.
RCT Entities:
PURPOSE: Optimal duration of adjuvant chemotherapy in the treatment of early-stage breast cancer remained to be investigated rigorously for the standard regimens in widespread use in North America (doxorubicin/cyclophosphamide, AC) and Europe (5-fluorouracil/epirubicin/cyclophosphamide, FEC). Whether six cycles of FEC 100 present an advantage, or not, compared with only four cycles was tested directly in a phase III prospective multicentre trial. PATIENTS AND METHODS: Between 2002 and 2006, 1515 women between 18 and 65°years of age, with node negative N(-) high-risk early-stage breast cancer, were included in the study following breast surgery and axillary lymph node dissection or procedure by sentinel node technique. Inclusion in the study required tumour size T ≥ 1 cm and at least one of the high-risk factors: T > 2 cm, negative oestrogen receptor/progesterone receptor (ER- and PR-), Scarff-Bloom-Richardson (SBR) grade II or III and age ≤ 35°years. Patients were randomly assigned to either six FEC 100 (Arm A) or four FEC 100 (Arm B). The trial was powered to detect an absolute difference ≥6% in disease-free survival (DFS) at 5°years. RESULTS: At 6.1°years median follow-up, with 91 (12%) events recorded in Arm A versus 106 (14%) in Arm B, no statistically significant risk increase was associated with four versus six FEC 100: DFS (hazard ratio (HR) = 1.18; CI 95% [0.89-1.56], P = .24) and overall survival (OS) (HR = 1.39; CI 95% [0.91-2.13], P = .12). CONCLUSION: Differences in chemotherapy duration did not induce notably different outcomes in our cohort of high-risk patients. CLINICAL TRIAL REGISTRY NUMBER: NCT00055679, Agence National de Sécurité du Médicament (ANSM) - France.