P E Goss1, J N Ingle2, S Martino3, N J Robert4, H B Muss5, R B Livingston6, N E Davidson7, E A Perez8, Y Chavarri-Guerra9, D A Cameron10, K I Pritchard11, T Whelan12, L E Shepherd13, D Tu13. 1. Cancer Center, Massachusetts General Hospital, Boston. Electronic address: pgoss@partners.org. 2. Division of Medical Oncology, Department of Oncology, Mayo Clinic, Rochester. 3. Breast Cancer Division, Los Angeles Clinic and Research Institute, Santa Monica. 4. Virgina Cancer Specialists, Inova Fairfax Hospital, Virgina. 5. Department of Medicine and Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill. 6. University of Washington, Seattle. 7. Cancer Institute and UPMC Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh. 8. Mayo Clinic Cancer Center, Jacksonville, USA. 9. Cancer Center, Massachusetts General Hospital, Boston. 10. Edinburgh Breast Unit, Western General Hospital and, University of Edinburgh, Edinburgh, UK. 11. Sunnybrook Odette Regional Cancer Centre, University of Toronto, Toronto. 12. Department of Oncology, McMaster University, Hamilton. 13. National Cancer Institute of Canada, Clinical Trials Group, Kingston, Canada.
Abstract
BACKGROUND: MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen. PATIENTS AND METHODS: Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis. RESULTS: At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03). CONCLUSIONS: Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.
RCT Entities:
BACKGROUND: MA17 showed improved outcomes in postmenopausal women given extended letrozole (LET) after completing 5 years of adjuvant tamoxifen. PATIENTS AND METHODS: Exploratory subgroup analyses of disease-free survival (DFS), distant DFS (DDFS), overall survival (OS), toxic effects and quality of life (QOL) in MA17 were performed based on menopausal status at breast cancer diagnosis. RESULTS: At diagnosis, 877 women were premenopausal and 4289 were postmenopausal. Extended LET was significantly better than placebo (PLAC) in DFS for premenopausal [hazard ratio (HR) = 0.26, 95% confidence interval (CI) 0.13-0.55; P = 0.0003] and postmenopausal women (HR = 0.67; 95% CI 0.51-0.89; P = 0.006), with greater DFS benefit in those premenopausal (interaction P = 0.03). In adjusted post-unblinding analysis, those who switched from PLAC to LET improved DDFS in premenopausal (HR = 0.15; 95% CI 0.03-0.79; P = 0.02) and postmenopausal women (HR = 0.45; 95% CI 0.22-0.94; P = 0.03). CONCLUSIONS: Extended LET after 5 years of tamoxifen was effective in pre- and postmenopausal women at diagnosis, and significantly better in those premenopausal. Women premenopausal at diagnosis should be considered for extended adjuvant therapy with LET if menopausal after completing tamoxifen.
Authors: Paul E Goss; James N Ingle; Silvana Martino; Nicholas J Robert; Hyman B Muss; Martine J Piccart; Monica Castiglione; Dongsheng Tu; Lois E Shepherd; Kathleen I Pritchard; Robert B Livingston; Nancy E Davidson; Larry Norton; Edith A Perez; Jeffrey S Abrams; Patrick Therasse; Michael J Palmer; Joseph L Pater Journal: N Engl J Med Date: 2003-10-09 Impact factor: 91.245
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