Optimal duration of adjuvant chemotherapy for high-risk node-negative (N–) breast cancer patients: 6-year results of the prospective randomised multicentre phase III UNICANCER-PACS 05 trial (UCBG-0106)

• Published in: European journal of cancer (1990) 2017-07, Vol.79, p.166-175
• Main Authors: Kerbrat, Pierre, Desmoulins, Isabelle, Roca, Lise, Levy, Christelle, Lortholary, Alain, Marre, Alain, Delva, Rémy, Rios, Maria, Viens, Patrice, Brain, Étienne, Serin, Daniel, Edel, Magali, Debled, Marc, Campone, Mario, Mourret-Reynier, Marie-Ange, Bachelot, Thomas, Foucher-Goudier, Marie-Josèphe, Asselain, Bernard, Lemonnier, Jérôme, Martin, Anne-Laure, Roché, Henri
• Format: Article
• Language: English
• Subjects: 5-Fluorouracil; Adjuvant chemotherapy; Adolescent; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer; Chemotherapy; Chemotherapy duration; Chemotherapy, Adjuvant - adverse effects; Chemotherapy, Adjuvant - methods; Chemotherapy, Adjuvant - mortality; Clinical trials; Cyclophosphamide; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Doxorubicin; Epirubicin; Epirubicin - administration & dosage; Epirubicin - adverse effects; FEC 100; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; France - epidemiology; Health risks; Hematology, Oncology and Palliative Medicine; High-risk patients; Humans; Kaplan-Meier Estimate; Lymph nodes; Middle Aged; Node-negative; Optimization; Patients; Progesterone; Prospective Studies; Receptor, ErbB-2 - metabolism; Risk analysis; Risk Factors; Risk groups; Statistical analysis; Surgery; Survival; Treatment Outcome; Tumor Burden; Tumors; Young Adult
• ISSN: 0959-8049; 1879-0852
• DOI: 10.1016/j.ejca.2017.03.004

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.