Nonmyeloablative allogeneic hematopoietic stem cell transplantation for metastatic breast cancer

Previously, there was very little interest in investigating allogeneic hematopoietic stem cell transplantation (alloHSCT) in breast cancer because of the significant morbidity and mortality associated with this procedure, as well as the disappointing results observed in clinical trials with high-dose chemotherapy and autologous hematopoietic stem cell transplantation in advanced breast cancer. However, the development of nonmyeloablative (reduced-intensity) conditioning regimens, which have less treatment-related mortality but preserve the T cell-mediated graft-versus-tumor (GVT) effect, has led to the investigation of nonmyeloablative alloHSCT in diseases that had not previously been considered for conventional alloHSCT, including metastatic breast cancer. Laboratory data demonstrate that T cell-mediated responses to breast cancer that inhibit tumor growth are possible and provide the rationale to pursue allogeneic adoptive cellular therapy as a strategy to eliminate breast cancer. Early reports of nonmyeloablative alloHSCT indicate that a clinical GVT effect against breast cancer does exist. The responses appear to be dependent on the development of complete donor lymphoid chimerism, and responses may be delayed. The results from these initial trials must be interpreted cautiously. It is unlikely that nonmyeloablative alloHSCT by itself will result in complete eradication of metastatic breast cancer; however, it may serve as a therapeutic platform to enhance the effects of currently available immunotherapies (eg, trastuzumab administration) and complement existing cytotoxic therapies. Well-designed studies will be necessary to determine the clinical efficacy of nonmyeloablative alloHSCT as adoptive cellular therapy in metastatic breast cancer.