Trastuzumab, Cyclophosphamide, and Vaccine Therapy in Treating Patients With High-Risk or Metastatic Breast Cancer

OBJECTIVES: Primary * To evaluate the safety of allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine in combination with trastuzumab (Herceptin®) and cyclophosphamide in patients with high-risk or metastatic HER2/neu-overexpressing breast cancer. * To measure the HER2/neu-specific CD4+ T-cell response by delayed-type hypersensitivity. * To measure the magnitude of HER2/neu-specific CD8+ T-cell responses by ELISPOT. Secondary * To assess the impact of trastuzumab on immune priming in vivo by IHC. * To measure the impact of cyclophosphamide pretreatment on CD4+CD25+ regulatory T cells by flow cytometry. * To determine the time to disease progression. Tertiary * To develop the tandem tetramer/CD107a cytotoxicity assay for HER2/neu-specific CD8+ T cells. * To measure novel T-cell responses induced by trastuzumab and cyclophosphamide-modulated vaccination. OUTLINE: Patients receive trastuzumab (Herceptin®) IV over 30-90 minutes once weekly beginning on day -1 of the first course of vaccination and continuing until the completion of the last course of vaccination. Patients also receive cyclophosphamide IV over 30 minutes on day -1 and allogeneic sargramostim (GM-CSF)-secreting breast cancer vaccine intradermally on day 0. Treatment with cyclophosphamide and the vaccine repeats every 27-42 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients then receive a fourth course of cyclophosphamide and vaccine approximately 6-8 months after the first course. Patients undergo delayed-type hypersensitivity testing and blood sample collection at baseline and periodically during study for immunologic laboratory studies. Blood samples are analyzed for serum GM-CSF levels by pharmacokinetic studies and for immune monitoring by ELISPOT and flow cytometry. Skin punch biopsies are also performed periodically and analyzed by IHC. After completion of study treatment, patients are followed periodically.