High-Dose Chemotherapy with Autologous Stem Cell Rescue as a Treatment Modality for Breast Cancer

Retrospective analyses of clinical trials as well as several prospective randomized clinical trials designed to evaluate dose intensity have emphasized the importance of intensive chemotherapy in determining outcomes in breast cancer treatment. One strategy that can deliver a large increment in dose intensity is high-dose chemotherapy with autologous stem cell transplantation (HDC-ASCT), since it overcomes myelosuppression, a major dose-limiting toxicity of most chemotherapy regimens. Phase II data from HDC-ASCT trials have indicated improved complete remission rates and longer remission duration when compared to historical conventional-dose chemotherapy regimens. With declining treatment-related mortality (TRM) through improvements in supportive care and innovations in stem cell collection procedures, exploration of HDC-ASCT in prospective randomized trials has been made possible. Several prospective randomized trials have completed accrual and early results are now available, while other studies are still ongoing. Unfortunately the trial designs are quite varied, the characteristics of patients differ from study to study, the early data provide conflicting results, and the follow-up is quite short, making firm conclusions impossible at present. Of note, the comparison arms in several of the studies are performing better than historical nontransplant treatments, perhaps a result of an intermediate dose intensity employed in the nontransplant arm of these trials. These data suggest that dose intensity, whether supported by stem cells or hematopoietic growth factors, may be quite important in optimizing treatment outcomes, affirming earlier concepts of the importance of dose intensity. Further follow-up of the current clinical trials and analyses of ongoing studies not yet reported are necessary before firm conclusions are possible as to the optimal strategy of using dose intensity in the management of breast cancer.