Clinical Trial: Hematopoietic Progenitor Cell Transplantation in Breast Cancer: Current Status and Future Directions

Abstract

Breast cancer remains the second leading cause of cancer death despite numerous advances in medical science. In vitro, preclinical, and clinical trials have shown that chemotherapy dose intensity is an important component of therapy. Many clinical trials addressing the use of high-dose chemotherapy and hematopoietic cellular rescue have been conducted over the past decade. Early trials undertaken in heavily pretreated patients who had metastatic disease were associated with high treatment-related mortality rates; good response rates were noted but overall survivals were short. Subsequent technological advances, including the use of recombinant hematopoietic growth factors and peripheral blood progenitor cells as the source of cellular rescue, have dramatically lowered the morbidity and mortality of the procedure, as well as shortened hospital stay and markedly reduced cost. As a result, the high-dose chemotherapy approach has been used earlier in the disease course, both in patients with metastatic disease who were responding and in the adjuvant setting in patients at high risk for relapse. Results of many of these phase II trials are extremely encouraging, and phase III prospective, randomized trials comparing auto-transplant to conventional approaches are currently under way. This review discusses past, current, and future initiatives of this modality. Included is a discussion of new preparative regimens, the addition of agents such as biochemical modifiers to enhance antitumor activity, and issues regarding timing of auto-transplant, stem cell technology, use of allogeneic stem cells, and posttransplantation therapies.

Key Words:

• Breast cancer
• High-dose chemotherapy
• Human bone marrow
• Cytokines
• Stroma
• Immunotherapy
• Angiogenesis
• Hematopoietic progenitor cells
• Stem cells
• Autologous and allogeneic transplantation
• Tumor detection