Researchers affiliated with the MDACC-EBMT Meta-Analysis Group have reported that high-dose chemotherapy followed by autologous stem cell infusion modestly improves disease-free survival (DFS) but does not significantly improve overall survival (OS) among women with node-positive breast cancer. These results were presented at the 2007 San Antonio Breast Cancer Symposium.

Previous studies have produced conflicting results regarding outcomes in women with early-stage breast cancer who are treated with high-dose chemotherapy and stem cell transplant. Unfortunately, with the advent of newer chemotherapy agents and targeted therapies, it is difficult to ascertain the real value of high-dose therapy, as the high-dose regimens typically involved chemotherapy regimens that have since proven not to be the optimal regimens at standard doses.

To summarize the available evidence regarding high-dose chemotherapy and autologous stem cell transplant in women with node-positive breast cancer, researchers performed a meta-analysis including data from 15 previous randomized clinical trials. These clinical trials enrolled a total of more than 6,000 women, and had compared high-dose chemotherapy regimens to standard-doses. The median age was 46 years, and the median follow-up was six years.  Average weekly dose intensity and total dose intensity were factors considered to account for variations between trials.

• Women treated with high-dose chemotherapy did not achieve a significant benefit in terms of overall survival (p=0.21).
• Disease-free survival was improved with high-dose chemotherapy (HR = 0.87 in favor of the high-dose approach, P=0.0005).
• Breast cancer specific survival was not improved with high-dose chemotherapy.
• Analyses did indicate improved survival among patients with hormone-receptor negative, and HER2-negative breast cancers (P = .0085).
• After adjusting for hormone receptor status there was a modest benefit of high-dose therapy on breast cancer specific survival and overall survival.
• An important limitation of this analysis is that it did not have information about more recently-introduced treatments such as taxane chemotherapy drugs or targeted therapies.

The researchers conducting this meta-analysis concluded that high-dose chemotherapy and autologous stem cell transplantation did not improve survival for early-stage, node-positive breast cancer.

Comments: Although it is difficult to accurately assess the benefit of high-dose therapy with autologous stem cell transplantation with newer therapeutic regimens, these results do not support the use of high-dose chemotherapy for the adjuvant treatment of breast cancer outside of a clinical trial. These data would suggest that the delivery of one or two high-dose treatments has less of an impact on breast cancer than on hematological malignancies such as lymphoma. Any new strategies for the use of stem cells to support chemotherapy would probably have to incorporate sequential chemotherapy treatments which appear to be necessary for prevention of recurrences in high-risk women with localized breast cancer.

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Reference: Berry DA, Ueno NT, Johnson MM et al. High-dose chemotherapy with autologous stem-cell support versus standard-dose chemotherapy: meta-analysis of individual patient data from 15 randomized adjuvant breast cancer trials. Presented at the 30th Annual San Antonio Breast Cancer Symposium. San Antonio, TX, December 13-16, 2007. Abstract #11.