Medline ® Abstract for Reference 27
of 'Adjuvant chemotherapy for HER2-negative breast cancer'
High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: overview of 15 randomized trials.
Berry DA, Ueno NT, Johnson MM, Lei X, Caputo J, Rodenhuis S, Peters WP, Leonard RC, Barlow WE, Tallman MS, Bergh J, Nitz UA, Gianni AM, Basser RL, Zander AR, Coombes RC, RochéH, Tokuda Y, de Vries EG, Hortobagyi GN, Crown JP, Pedrazzoli P, Bregni M, Demirer T
J Clin Oncol. 2011;29(24):3214. Epub 2011 Jul 18.
PURPOSE: Adjuvant high-dose chemotherapy (HDC) with autologous hematopoietic stem-cell transplantation (AHST) for high-risk primary breast cancer has not been shown to prolong survival. Individual trials have had limited power to show overall benefit or benefits within subsets.
METHODS: We assembled individual patient data from 15 randomized trials that compared HDC versus control therapy without stem-cell support. Prospectively defined primary end points were relapse-free survival (RFS) and overall survival (OS). We compared the effect of HDC versus control by using log-rank tests and proportional hazards regression, and we adjusted for clinically relevant covariates. Subset analyses were by age, number of positive lymph nodes, tumor size, histology, hormone receptor (HmR) status, and human epidermal growth factor receptor 2 (HER2) status.
RESULTS: Of 6,210 total patients (n = 3,118, HDC; n = 3,092 control), the median age was 46 years; 69% were premenopausal, 29% were postmenopausal, and 2% were unknown menopausal status; 49.5% were HmR positive; 33.5% were HmR negative, and 17% were unknown HmR status. The median follow-up was 6 years. After analysis was adjusted for covariates, HDC was found to prolong relapse-free survival (RFS; hazard ratio [HR], 0.87; 95% CI, 0.81 to 0.93; P<.001) but not overall survival (OS; HR, 0.94; 95% CI, 0.87 to 1.02; P = .13). For OS, no covariates had statistically significant interactions with treatment effect, and no subsets evinced a significant effect of HDC. Younger patients had a significantly better RFS on HDC than did older patients.
CONCLUSION: Adjuvant HDC with AHST prolonged RFS in high-risk primary breast cancer compared with control, but this did not translate into a significant OS benefit. Whether HDC benefits patients in the context of targeted therapies is unknown.
Division of Quantitative Sciences, Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1402, USA. email@example.com