Autologous Stem Cell Transplantation Versus Standard or Dose-Dense Chemotherapy in High Risk Breast Cancer: A Systematic Review.
Authors: Herrmann-Frank A. , Sturtz S. , Lerch C. , Richter B. , Bartel C. , Droste S. , Kulig M. , Lange S. 
Published: December 2010

Abstract
Background/Objectives: The role of high dose chemotherapy followed by autologous stem cell transplantation (ASCT) for women with breast cancer is still a controversial issue. To-date, several randomized controlled trials (RCTs) have been completed, and for some trials follow-up data of more than 5 years are available. The aim of the current project was to review the available evidence deriving from RCTs and to determine the benefits and risks of ASCT for women with high risk breast cancer (HRBC), i.e. at least 4 involved axillary lymph nodes.Methods: We performed a systematic search in bibliographic databases (MEDLINE, EMBASE, BIOSIS Previews, The Cochrane Library) for RCTs comparing ASCT with standard (CTx) or dose dense chemotherapy (DD-CTx) as well as different ASCT strategies. In addition to clinical outcomes such as overall (OS) or disease-free survival (DFS) and toxicity, health-related quality of life (HRQL) was also analyzed. For meta-analysis, the random effects model was used. Only trials published in full text were considered for evaluation.Results: 13 trials with 5251 patients were available for analysis. 10 trials compared single ASCT with CTx, 1 ASCT with DD-CTx, and 2 tandem ASCT with CTx or DD-CTx, respectively. Single ASCT significantly prolonged DFS or a similar outcome compared to CTx. At 5 years, the meta-analysis, including 9 out of 10 trials for this comparison, revealed an absolute difference in rates of DFS of -0.05 (95% CI [-0.08; -0.01]), p=0.007, in favor of ASCT. Grade 3-5 toxicity, however, was also increased in the single ASCT groups. Tandem ASCT was superior to DD-CTx for the outcomes OS and event-free survival (EFS): 5-years OS (ASCT/DD-CTx) = 73%/59%, p= 0.02 (log rank test); 5-years EFS (ASCT/DD-CTx) = 55%/37%, p= &lt;0.001 (log rank test). Since this superiority was only observed in 1 trial (WSG AM-01), this advantage of tandem ASCT might be strongly related to the therapy protocol applied. HRQL data could be extracted from 5 trials comparing single ASCT with CTx. Scores of some HRQL indicators were significantly lower in the transplantation arm during the first months after therapy, suggesting a harm of ASCT, but results were similar at ≥1 year. Subgroup analysis indicated a benefit of ASCT for younger patients. The exact age limit – 40 or 50 years – remains to be determined. Further subgroup analyses either suffered from the lack of interaction tests or were based on the results of single trials.Summary/Conclusions: The data presented provide a comprehensive systematic review for ASCT in HRBC, including the most recent results of RCTs published to May 2009. In summary, ASCT has at most a modest benefit for women with HBRC. Current evidence does not allow a reliable appraisal of the benefit of ASCT for subgroups of HRBC patients. Benefits and risks of ASCT should be weighted in the context of contemporary therapy protocols. Since ASCT in breast cancer was introduced into health care on a vague clinical data basis, further evaluation should only be performed within the framework of clinical trials.
Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2096.