DESCRIPTION (Applicant's Description) The overall goal of this proposal is to improve the long-term disease-free survival of patients with metastatic breast cancer. While the use of high-dose chemotherapy followed by AHPCS may improve the survival of patients with metastatic breast cancer, the vast majority of these patients ultimately relapse and die of their disease. The use of RIT has shown great promise for the treatment of lymphomas and other hematologic malignancies. This may not be surprising given the marked sensitivity of lymphoma cells to irradiation. Fewer studies have been conducted in patients with solid tumors, largely because toxicity to the bone marrow precluded dose escalation of the radiolabel. We previously conducted a small phase I study using a mouse monoclonal antibody BrE-3 in patients with breast cancer that had failed conventional or high-dose chemotherapy. Results were very encouraging with no non-hematologic toxicities and a 50 percent response rate. We propose to conduct a phase I study of high-dose radloimmunotherapy using the anti-breast cancer monoclonal antibody humanized-BrE-3 labeled with 90-Yttrium followed by AHPCS in patients with metastatic breast cancer that are refractory to conventional chemotherapy. BrE-3 labeled with 111-Indium will be used for imaging in these patients. The clinical endpoints of the study will be to define the maximum tolerated dose and dose limiting toxicities of the radioimmunoconjugate. In addition, we will study the dosimetry and pharmacokinetics of the radiolabel and we will also obtain preliminary estimates of its efficacy in preparation for a phase II study in the future.