Six Cycles of Doxorubicin and Cyclophosphamide or Paclitaxel Are Not Superior to Four Cycles As Adjuvant Chemotherapy for Breast Cancer in Women With Zero to Three Positive Axillary Nodes: Cancer and Leukemia Group B 40101

• Type of Material: Article
• Authors: Lawrence N. Shulman, Dana-Farber Cancer Institute; Constance T. Cirrincione, Duke University; Donald A. Berry, University of Texas; Heather P. Becker, Cancer and Leukemia Group B Central Office; Edith A. Perez, Mayo Clinic; Ruth O'Regan, Emory University; Silvana Martino, Angeles Clinic & Research Institute; James N. Atkins, Community Clinical Oncology Program, Goldsboro; Erica Mayer, Dana-Farber Cancer Institute; Charles J. Schneider, Christiana Healthcare Services; Gretchen Kimmick, Duke University; Larry Norton, Memorial Sloan-Kettering Cancer Center; Hyman Muss, University of North Carolina; Eric P. Winer, Dana-Farber Cancer Institute; Clifford Hudis, Memorial Sloan-Kettering Cancer Center
• Language: English
• Date: 2012-11-20
• Publisher: American Society of Clinical Oncology
• Publication Version: Final Published Version
• Copyright Statement: © 2012 by American Society of Clinical Oncology
• Final Published Version (URL): http://dx.doi.org/10.1200/JCO.2011.40.6405
• Title of Journal or Parent Work: Journal of Clinical Oncology
• ISSN: 0732-183X
• Volume: 30
• Issue: 33
• Start Page: 4071
• End Page: 4076
• Grant/Funding Information: Supported by Grants No. CA25224, CA21115, CA32102, CA32291, CA33601, CA45808, CA45418, CA47577, CA77651, and CA47559 from the National Cancer Institute.
• Keywords: SURVIVAL; EPIRUBICIN; RANDOMIZED-TRIAL; Oncology; THERAPY; PLUS CYCLOPHOSPHAMIDE; TAMOXIFEN; METHOTREXATE; FLUOROURACIL; Life Sciences & Biomedicine; HIGH-RISK; DOCETAXEL; Science & Technology
• Research Categories: Health Sciences, Oncology; Health Sciences, Epidemiology; Health Sciences, Pharmacology

Abstract

PURPOSE: The ideal duration of adjuvant chemotherapy for patients with lower risk primary breast cancer is not known. Cancer and Leukemia Group B trial 40101 was conducted using a phase III factorial design to define whether six cycles of a chemotherapy regimen are superior to four cycles. We also sought to determine whether paclitaxel (T) is as efficacious as doxorubicin/cyclophosphamide (AC), but with reduced toxicity. PATIENTS AND METHODS: Between 2002 and 2008, the study enrolled women with operable breast cancer and zero to three positive nodes. Patients were randomly assigned to either four or six cycles of either AC or T. Study stratifiers were estrogen receptor/progesterone receptor (ER/PgR), human epidermal growth factor receptor 2 (HER2), and menopausal status. After 2003, all treatment was administered in dose-dense fashion. The primary efficacy end point was relapse-free survival (RFS). RESULTS: A total of 3,171 patients were enrolled; 94% were node-negative and 6% had one to three positive nodes. At a median follow-up of 5.3 years, the 4-year RFS was 90.9% and 91.8% for six and four cycles, respectively. The adjusted hazard ratio (HR) of six to four cycles regarding RFS was 1.03 (95% CI, 0.84 to 1.28; P=.77). The 4-year OS was 95.3% and 96.3% for six and four cycles, respectively, with an HR of six to four cycles of 1.12 (95% CI, 0.84 to 1.49; P=.44). There was no interaction between treatment duration and chemotherapy regimen, ER/PgR, or HER2 status on RFS or OS. CONCLUSION: For women with resected primary breast cancer and zero to three positive nodes, we found no evidence that extending chemotherapy regimens of AC or single-agent T from four to six cycles improves clinical outcome.