Two meta-analyses published early online by the Journal of Clinical Oncology examine the evidence on high-dose chemotherapy with stem-cell support in high-risk primary and in metastatic breast cancer: both found that while the technique produced small increases in relapse-free survival, it did not significantly prolong overall survival.

It is intuitively attractive that increasing the intensity of chemotherapy in patients with cancer should improve outcomes providing toxicity can be overcome, and techniques that combined high dose chemotherapy regimens with autologous bone-marrow stem-cell transplant to reduce haematological toxicity became popular despite limited evidence for benefit. The authors of these two reports aimed to summarise the evidence for use of the technique in high risk primary and in metastatic breast cancer using systematic review and meta-analysis.

In the first report, the authors searched for studies that compared adjuvant high-dose chemotherapy (HDC) with autologous haematopoietic stem-cell transplantation (AHST) against control therapy without stem-cell support in patients with high-risk primary breast cancer. They obtained patient-level data from included trials to allow subgroup analysis.

There were 15 eligible studies involving 6,210 patients in total (HDC, n=3,118; control n= 3,092). Median follow-up was 6 years, and during this period 50% (3,082) of patients had recurrence and 40% (2,468) died. After adjustment for potential confounding factors, HDC was associated with a small, but statistically significant increase in relapse-free survival with a hazard ratio (HR) of 0.87 (95% CI, 0.81 to 0.93; P < 0.001). It was not, however, associated with a significant improvement in overall survival (HR, 0.94; 95% CI, 0.87 to 1.02; P = 0.13) and patients who had HDC and did have recurrence had a significantly higher risk of death (HR, 1.16; 95% CI, 1.07 to 1.26; P<0.001). There were no subgroups that could be identified in which the outcomes were significantly better.

The second study examined the evidence for HDC in metastatic breast cancer, also using patient-level data. The authors located six eligible trials with a total of 886 participants (HDC, n=447; control n= 419). In this analysis also there was no significant difference in overall survival, with a median 2.16 years for HDC vs. 2.02 years for control (P = 0.08), and a small but statistically significant difference in progression-free survival (median, 0.91 v 0.69 years respectively; HR for survival 0.76; 95% CI, 0.66 to 0.88; P<0.001). Subgroup analysis suggested possible statistically significant benefits in some subgroups, however the differences were small and not robust due to the small numbers. The authors of both analyses conclude that HDC with stem-cell support in patients with high-risk primary or metastatic breast cancer produced small increases in progression-free survival that did not translate into improved overall survival. Neither analysis was able to identify a subgroup of patients with clear benefit from the therapy. The authors note that the results are consistent with a small increase in chance of overall survival in the range 5% to 10%, and apply only to the drug regimens included in the trials.

An editorial discussing the analysis of the metastatic breast cancer studies has also been published.