Allogeneic transplantation in metastatic breast cancer: Rationale for use of nonmyeloablative preparative regimens

Allogeneic hematopoietic transplantation results in engraftment of the donor lympho-hematopoietic system, which can potentially mediate an immune antitumor effect. Pilot studies of allogeneic transplantation have been conducted in metastatic breast cancer to test the hypothesis that allogeneic cells (graft) can eliminate breast cancer cells via this graft-versus-breast cancer effect. Both conventional therapies (standard-dose chemotherapy, hormonal therapy) and high-dose chemotherapy (HDCT) with autologous transplantation have been extensively evaluated as treatment for breast cancer. These approaches may produce complete remission (CR), but relapse remains the major problem because of incomplete eradication of the disease. Few patients with metastatic disease are long-term survivors. In hematological malignancies, the success of allogeneic transplantation depends on induction of graft-versus-malignancy (GVM) effects, which are well documented against leukemias, multiple myeloma, and non-Hodgkin's lymphomas. It is uncertain, however, whether similar GVM effects against breast cancer occur. The preliminary studies of allogeneic transplantation for metastatic breast cancer showed the feasibility of this procedure to achieve hematopoietic chimerism. Further, regression of breast cancer has been observed when associated with the development of graft-versus-host disease (GVHD), which is consistent with the existence of GVM effects. Allogeneic hematopoietic transplants generally use a HDCT preparative regimen. If GVM effects are sufficient to prevent recurrence of disease, intensive myeloablative therapy may not be necessary. Nonmyeloablative preparative regimens with reduced toxicity have recently been evaluated for allogeneic transplantation; these regimens are designed to allow engraftment of donor hematopoietic cells with much less toxicity than the typical ablative preparative regimens used before allogeneic transplant. This approach, using nonmyeloablative preparative regimens with allogeneic transplantation, is currently under study in patients with chemotherapy-sensitive metastatic breast cancer. In this article, we review the rationale, latest experience, and future directions in using allogeneic transplantation for this disease. Copyright (C) 2000 by W.B. Saunders Company.