S Aebi1, Z Sun2, D Braun2, K N Price3, M Castiglione-Gertsch4, M Rabaglio5, R D Gelber6, D Crivellari7, J Lindtner8, R Snyder9, P Karlsson10, E Simoncini11, B A Gusterson12, G Viale13, M M Regan2, A S Coates14, A Goldhirsch15. 1. Division of Medical Oncology, Berne University Hospital and Swiss Group for Clinical Cancer research (SAKK), Berne, Switzerland. Electronic address: stefan.aebi@onkologie.ch. 2. IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Harvard School of Public Health, Boston. 3. IBCSG Statistical Center and Frontier Science and Technology Research Foundation, Boston, USA. 4. Medical Onco-Gynecology Unit, Department of Medicine, Geneva University Hospital, Geneva. 5. IBCSG Coordinating Center and Inselspital, Berne, Switzerland. 6. IBCSG Statistical Center, Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Frontier Science and Technology Research Foundation, Harvard School of Public Health, Harvard Medical School, Boston, USA. 7. Department of Medical Oncology, Centro di Riferimento Oncologico, Aviano, Italy. 8. Department of Surgical Oncology, Institute of Oncology, Ljulbljana, Slovenia. 9. Department of Medical Oncology, St Vincent's Hospital, Melbourne, Australia. 10. Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy at University of Gothenburg, Sahlgrenska University Hospital, Gothenburg, Sweden. 11. Department of Medical Oncology, Spedali Civili di Brescia, Brescia, Italy. 12. IBCSG Pathology Review Office, Institute of Cancer Sciences, University of Glasgow, Glasgow, UK. 13. IBCSG Pathology Office, Division of Pathology and Laboratory Medicine, European Institute of Oncology, University of Milan, Milan, Italy. 14. International Breast Cancer Study Group, Berne, Switzerland; School of Public Health, University of Sydney, Australia. 15. Department of Medicine, European Institute of Oncology, Milan, Italy; Department of Medical Oncology, Oncology Institute of Southern Switzerland, Bellinzona, Switzerland.
Abstract
BACKGROUND: The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed. PATIENTS AND METHODS: After stratification by ER status, 1669 postmenopausal patients with operable lymph node-negative breast cancer were randomly assigned to three 28-day courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF→tamoxifen) or to tamoxifen alone for 5 years. RESULTS: ERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF→tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes. CONCLUSION:CMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy.
RCT Entities:
BACKGROUND: The benefit of adjuvant chemotherapy in postmenopausal patients with estrogen receptor (ER)-positive lymph node-negative breast cancer is being reassessed. PATIENTS AND METHODS: After stratification by ER status, 1669 postmenopausal patients with operable lymph node-negative breast cancer were randomly assigned to three 28-day courses of 'classical' CMF (cyclophosphamide, methotrexate, 5-fluorouracil) chemotherapy followed by tamoxifen for 57 months (CMF→tamoxifen) or to tamoxifen alone for 5 years. RESULTS: ERs were positive in 81% of tumors. At a median follow-up of 13.1 years, patients with ER-positive breast cancers did not benefit from CMF [13-year disease-free survival (DFS) 64% CMF→tamoxifen, 66% tamoxifen; P = 0.99], whereas CMF substantially improved the prognosis of patients with ER-negative breast cancer (13-year DFS 73% versus 57%, P = 0.001). Similarly, breast cancer-free interval (BCFI) was identical in the ER-positive cohort but significantly improved by chemotherapy in the ER-negative cohort (13-year BCFI 80% versus 63%, P = 0.001). CMF had no influence on second nonbreast malignancies or deaths from other causes. CONCLUSION: CMF is not beneficial in postmenopausal patients with node-negative ER-positive breast cancer but is highly effective within the ER-negative cohort. In the future, other markers of chemotherapy response may define a subset of patients with ER-positive tumors who may benefit from adjuvant chemotherapy.
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