High-dose chemotherapy with hematopoietic rescue in breast cancer: from theory to practice

The development of more effective treatment strategies currently provides the only realistic hope of reducing breast cancer mortality. Among such treatments, high-dose chemotherapy (HDC) has been proposed to be a potentially curative strategy. Consideration of the factors involved in the successful treatment of human tumors suggests that HDC could be integrated into the treatment of breast cancer, but only if the treatment is adequately planned with regard to tumor kinetics and chemotherapy sensitivity and resistance patterns. Two randomized studies of the use of HDC in breast cancer have been published recently. In the first, HDC using a combination of cyclophosphamide, mitoxantrone, and etoposide as initial treatment was compared to a conventional dose regimen consisting of cyclophosphamide, mitoxantrone, and vincristine. The second study compared the effects of early or delayed HDC in patients who had an optimal response to conventional-dose induction chemotherapy. Both studies showed HDC to be more effective than conventional-dose treatment in delaying the time to progression, but only in the study in which HDC was used as the initial treatment was there an effect on survival. The differences between these two investigations can probably be explained on the basis of the different effects of the treatment regimens on tumor kinetics and the efficiency of HDC when used as salvage therapy in the delayed HDC group. Dose-intensive therapy has an established role in breast cancer. Attention now needs to focus on methods of optimizing this treatment strategy.