High-dose chemotherapy with autologous stem-cell support as adjuvant therapy in breast cancer: Overview of 15 randomized trials

Donald A. Berry, Naoto T. Ueno, Marcella M. Johnson, Xiudong Lei, Jean Caputo, Sjoerd Rodenhuis, William P. Peters, Robert C. Leonard, William E. Barlow, Martin S. Tallman, Jonas Bergh, Ulrike A. Nitz, Alessandro M. Gianni, Russell L. Basser, Axel R. Zander, R. Charles Coombes, Henri Roché, Yutaka Tokuda, Elisabeth G E De Vries, Gabriel N. HortobagyiJohn P. Crown, Paolo Pedrazzoli, Marco Bregni, Taner Demirer

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)3214-3223
Number of pages10
JournalJournal of Clinical Oncology
Issue number24
Publication statusPublished - Aug 20 2011

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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