Secondary Endpoints: 1. Overall survival for all patients will be followed . Surv ival for the Stage IV breast cancer patients will be compared to historical control. This study will not enroll sufficient numbers of subjects to give statistical power to this endpoint. However, a large difference observed between the treatment group and historical control would give additional impetus for a phase II study of efficacy. Although the study will enroll both breast and ovarian cancer patients, from our extensive experience in combined breast and ovarian cancer vaccine studies for HER2 , we a nticipate approximately 80% of the subjects enrolled will be Stage IV breast cancer patients. 6304p Protocol 118 04/06/2016 Appendices Appendix A ECOG Performance Scale Appendix B Laboratory Assays for Measuring Immune Response Appendix C Data Safety Monitoring Plan Appen dix D Supplemental HER2 CTL Peptide -Based Booster Vaccine Study 6304p Protocol 118 04/06/2016 Abbreviations: APC antigen presenting cells BUN blood urea nitrogen CBC complete blood count CFC cytokine flow cytometry CTL cytotoxic T lymphocytes DC dendritic cells DLN draining l ymph node DLT Dose limiting toxicity DSMP Data Safety Monitoring Plan ECD extracellular domain of HER2 FISH fluorescent in situ hybridization GM-CSF granulocyte macrophage colony stimulating factor HER2 HER -2/neu ICD intracellular domain of HER2 id. intradermal IFN interferon IHC immunohistochemistry LC Langerhans cells LV left ventricular MHC Major Histocompatability Complex NED no evidence of disease OS overall survival PBMC peripheral blood mononuclear cells SI stimulation index sc subcutaneous Th T helper cells UA urinanalysis UPN unique patient number 6304p Protocol 118 04/06/2016 List of Figures Figure 1. Patients with HER2 overexpressing cancers can be immunized with the HER2 CTL vaccine. Figure 2. The magnitude of HER2 specific CD8 T cell immunity is dep endent on T helper immunity Figure 3. Epitope spreading occurs with active immunization Figure 4. Patients immunized with a HER2 CTL vaccine develop persistent immunity and epitope spreading years after active immunizations have ended Figure 5. Overall survival in HER2+ Stage IV breast cancer patients Figure 6. The use of HER2 peptide based vaccines in the adjuvant setting may impact survival in patients with advanced stage HER2 overexpressing breast cancer Figure 7. Treatment of HER2+ tumor cells with trastuzumab in vitro enhances lysis of HER2+/A2+ tumor cells by T clones specific for p369- 377. 6304p Protocol 118 04/06/2016 1. Introduction The HER -2/neu (HER2) oncogenic protein is a well defined tumor antigen in patients with breast cancer. Monoclonal antibody therapy with agent s such as trastuzumab, targeting the HER2 protein, has demonstrated a survival benefit for patients with advanced stage breast cancer. We have completed a phase I study of a HER2 peptide -based vaccine designed to elicit both T helper (Th) and cytotoxic T cell (CTL) responses. In an evaluation of 20 patients the vaccine was safe, was not associated with toxicity, particularly autoimmune toxicity, and was immunogenic. Patients immunized developed T cell immunity directed against HER2. Specifically, HER2 s pecific CTL from patients post -vaccination lysed HLA -matched HER2 overexpressing tumors. Moreover, the immunization strategy was designed to augment both HER2 specific CD4+ and CD8+ immune responses and, indeed, long -lived immunologic memory was created i n a substantial number of the patients vaccinated. Since this initial study, standard of care for advanced stage HER2+ breast cancer patients includes trastuzumab administered with chemotherapy. Furthermore, patients with Stage IV HER2 overexpressing ovarian cancer have received trastuzumab as part of their therapy. For patient’s who achieve a complete remission (CR) or stabilization of disease, treatment with trastuzumab alone continues for several months to a year or until progression. For this reason, a HER2 specific vaccine aimed at preventing relapse in stage IV breast cancer patients after standard therapy will have to be given concurrently with trastuzumab. The concurrent administration of trastuzumab with a HER2 CTL vaccine may actually make the vaccine more effective in eliciting HER2 specific CTL responses. The internalization of the HER2 receptor after binding to the antibody would potentially increase presentation of processed HER2 proteins in MHC class I molecules. Indeed, recent studies h ave shown that pretreatment of HER2 overexpressing tumor cells with trastuzumab makes them more susceptible to lysis by HER2 specific CTL T cell clones . (1) The proposed clinical trial is a phase I/II study of combination immunotherapy for the generation of HER2 specific CTL in vivo . Trastuzumab will be given concurrently with a HER2 peptide based vaccine composed of Th epitopes that encompass within their natural sequence HLA -A2 binding epitopes of HER2. The strategy is to administer a vaccine that will stimulate both CD4+ and CD8+ responses simultaneously. The primary objectives of the study are to evaluate the safety of administering a HER2 CTL peptide -based vaccine to Stage IV breast and ovarian cancer patients receiving trastuzumab as well as to quantify and characterize antigen specific T cell subsets specific to HER2 in PBMC of patients after vaccination. A secondary objective is to evaluate time to overall survival (OS) in patients who complete a vaccination series with a HER2 CT L peptide - based vaccine while receiving trastuzumab. 2.