Allogeneic hematopoietic stem cell transplantation for metastatic breast cancer

Experimental Transplantation and Immunology Branch, National Cancer Institute, Building 10, Room 12N226 Bethesda, MD 20892, USA. mbishop@mail.nih.gov

The prognosis is poor and the options are limited for patients with metastatic breast cancer (MBC), especially for those patients who have previously received taxanes and anthracyclines; treatment strategies are primarily palliative. Murine models have demonstrated that allogeneic T cells are capable of eliciting graft-versus-tumor (GVT) effects against breast cancer, inhibiting growth of breast cancer cell lines in vivo, providing the rationale to pursue allogeneic adoptive cellular therapy as a strategy to treat MBC. However, the clinical application of allogeneic hematopoietic stem cell transplantation (alloHSCT) was limited by concerns over toxicity and unproven efficacy. The development of non-myeloablative (a.k.a. reduced-intensity) conditioning regimens, which have less treatment-related mortality but preserve the T-cell mediated GVT effects, led to increased investigation of alloHSCT in MBC. Early reports of non-myeloablative alloHSCT indicate that a clinical GVT effect against breast cancer does exist. The responses, observed in 20-40% of patients, appear to be associated with the development of complete donor lymphoid chimerism and may be delayed. In its current form, alloHSCT by itself is unlikely to result in complete eradication of MBC; however, it may serve as a therapeutic platform to complement and enhance the effects of existing cytotoxic therapies and immunotherapies (e.g. trastuzumab), as well as therapies under development (e.g. vaccines). Current data on alloHSCT for MBC should be interpreted cautiously and carefully used for the design of future studies to fully determine the clinical efficacy of this form of adoptive cellular therapy in MBC.