Allogenic Haematopoietic Cell Transplantation for Patients With Refractory "Triple Negative" Breast Cancer

Breast cancer (BC) is the most common cancer among women and approximately 45% of breast cancer patients develop metastatic disease that generally remains incurable with a median survival of approximately 18 to 24 months. A subpopulation emerging as having particularly poor prognosis is patients who have disease that is receptor negative for oestrogen, progestin and HER2/neu (triple receptor negative). Since no effective therapy is available in this setting of patients, the investigators propose allogeneic haematopoietic cell transplantation. Recent advances in allogeneic haematopoietic cell transplantation (HCT) have led to reduced intensity preparative regimens that are non-myeloablative and permit the development of sustained donor chimerism. As a result, regimen related organ toxicities (RROT), and consequently non-relapse mortality has been reduced. However, the incidence of acute and chronic graft-versus-host disease (aGVHD and cGVHD, respectively) has remained a major complication. Pre-clinical data, developed by the Stanford group, established that nonmyeloablative conditioning with total lymphoid irradiation (TLI) combined with depletive anti-T cell antibodies protects against GVHD by skewing peripheral T cell subsets to favour suppressive regulatory T cells. The current proposal is a Phase II study evaluating safety and activity of the allogeneic peripheral blood progenitor cell (PBPC) transplantation using TLI/ATG conditioning regimen, the kinetics of donor haematopoietic cell engraftment and chimerism, the incidence and severity of acute GVHD following allogeneic transplantation using the novel preparative regimen of TLI combined with antithymocyte globulin (ATG). Patients with triple negative breast cancer will be considered for transplantation using donor grafts from HLA-matched related donors. The preparative regimen of TLI combined with ATG is expected to result in high levels of sustained donor haematopoietic cell engraftment with a significantly reduced incidence of acute GVHD.