Chemotherapy and Peripheral Stem Cell Transplantation Followed by Trastuzumab in Treating Women With Metastatic Breast Cancer

OBJECTIVES: I. Determine the safety and toxicity profile, specifically cardiac toxicity, of trastuzumab (Herceptin) following high dose chemotherapy and autologous peripheral blood stem cell transplantation in women with metastatic breast cancer. II. Determine the time to disease progression and disease free survival in these patients when treated with this regimen. III. Determine the impact of trastuzumab (Herceptin) on minimal residual disease after autologous peripheral blood stem cell transplantation as evidenced by serial immunocytochemical analysis of bone marrow. IV. Determine the relationship between posttransplant reconstitution of antibody dependent cellular toxicity and the efficacy of trastuzumab (Herceptin) in these patients.

OUTLINE: This is a multicenter study. Patients undergo stem cell mobilization with growth factors alone (filgrastim (G-CSF) and/or sargramostim (GM-CSF)) or chemotherapy followed by growth factors (depending on center). Peripheral blood stem cells (PBSC) are then collected by leukapheresis. Patients then receive high dose chemotherapy consisting of cyclophosphamide IV over 1 hour and cisplatin IV over 72 hours on days -6 to -4 and carmustine IV on day -3 or cyclophosphamide IV, thiotepa IV, and carboplatin IV over 96 hours on days -7 to -4 (depending on center). PBSC are reinfused on day 0. Patients then receive trastuzumab IV over 30-90 minutes weekly for 1 year or until disease progression beginning 5-8 weeks after PBSC reinfusion.

PROJECTED ACCRUAL: A total of 70 patients will be accrued for this study.