High dose chemotherapy for poor prognosis breast cancer: systematic review and meta-analysis

BACKGROUND: High dose chemotherapy with autologous transplantation of bone marrow or peripheral stem cells (autograft) has been considered promising for treating poor prognosis breast cancer. We reviewed the relevant evidence. METHODS: We included randomised controlled trials comparing high dose chemotherapy and autograft with conventional chemotherapy for women with early poor prognosis breast cancer. We searched medical databases (Cochrane Library, MEDLINE, EMBASE), websites (co-operative cancer research groups, American Society of Clinical Oncologists) and citations of articles found, to September 2006. Where appropriate, data were pooled to obtain a relative risk, using a fixed effects model. Clinical, methodological and statistical heterogeneity were examined with sensitivity analyses. FINDINGS: Thirteen trials with 5064 women were included. There was a significant benefit in event-free survival for the high dose group at three years (RR 1.19 (95% CI 1.06, 1.19)) and four years (RR 1.24 (95% CI 1.03, 1.50)) and at five years this benefit approached statistical significance (RR 1.06 (95% CI 1.00, 1.13)). Overall survival rates were not significantly different at any stage of follow up. There were significantly more treatment-related deaths on the high dose arm (RR 8.58 (95% CI 4.13, 17.80)). Morbidity was higher in the high dose group but there was no significant difference in the incidence of second cancers. The high dose group reported significantly worse quality of life immediately after treatment, but there were few differences by one year. INTERPRETATION: There is insufficient evidence supporting routine use of high dose chemotherapy with autograft for treating early poor prognosis breast cancer.