New developments in high-dose chemotherapy for breast cancer

High-dose chemotherapy with autologous stem cell support as applied to the treatment of breast cancer has shown promise for over 15 years. Three main approaches have been used: (1) standard-dose induction chemotherapy followed by one or two cycles of myeloablative therapy, (2) multicycle nonablative combination chemotherapy, and (3) high-dose sequential chemotherapy using single agents at the maximum tolerated doses in rapid sequence. Each of these approaches has a strong biological rationale and is being pursued in randomized trials. Unfortunately, comparative data are limited and there is only one fully published randomized trial of the use of high-dose chemotherapy in metastatic breast cancer. This small study from South Africa showed a significant improvement in response rate and survival for women receiving high-dose chemotherapy compared to those given standard dose treatment. It is anticipated that results from larger studies in the USA and Europe evaluating the use of high-dose chemotherapy in metastatic breast cancer and in adjuvant treatment of poor-prognosis early-stage disease will be available within the next 2-3 years. A potentially important and related issue is that of tumor contamination of bone marrow and apheresis collections. Current data suggest that finding epithelial tumor cells with sensitive techniques (such as immunohistochemistry or polymerase chain reaction) gives prognostic information. However, it is not clear whether reinfusion of these cells after high-dose chemotherapy contributes to relapse of breast cancer. Unfortunately, understanding of the data is marred by a lack of standardization of assay methodology. Further work is needed to develop a widely accepted method for the detection of circulating tumor cells before the clinical relevance of such a finding can be meaningfully interpreted.