Patients must be HLA -A2. Rationale Data from tumor vaccine studies now indicate there might be survival advantages for patients who have received tumor -antigen specific vaccinations. Our group has demonstrated a potential survival advantage for patients with advanced stage HER2 overexpressing breast cancer immunized with a HER2 peptide based vaccine after being treated to maximal response or complete remission with standard therapy. R ecent studies have demonstrated that “sensitization” of HER2 overexpressing tumor cells with trastuzumab, in vitro , will enhance the function of CTL specific for HER2. Theoretically, the mechanism of trastuzumab’s enhancement of a HER2 specific CTL respon se might be the internalization of the HER2 receptor, degradation of the HER2 protein, and increased MHC -peptide presentation with a resultant increase in CD8+ HER2 specific CTL function. Thus, combination of trastuzumab with HER2 peptide based vaccine de signed to elicit CTL in the context of HLA -A2 may even further enhance the generation of a HER2 specific CTL response and potentially translate into improved survival for advanced stage breast and ovarian cancer patients when used in the adjuvant setting. This proposal outlines a clinical trial designed to utilize the potential synergistic effect between trastuzumab and a HER2 CTL generating peptide based vaccine (HER2 CTL vaccine) in order to increase CTL precursor frequencies that target HER2 specific epitopes. Patients will be treated to NED or stable disease with chemotherapy and trastuzumab or trastuzumab alone and while on maintenance trastuzumab receive vaccinations with a HER2 CTL vaccine. Objectives Primary : 1. To evaluate the safety of ad ministering a HER2 CTL peptide -based vaccine to Stage IV breast and ovarian cancer patients receiving maintenance trastuzumab. 2. To quantify and characterize antigen specific T cells directed against HER2 in PBMC of patients after vaccination with a HER CTL peptide -based vaccine administered while receiving maintenance trastuzumab. 6304p Protocol 118 04/06/2016 Secondary : 1. To evaluate overall survival (OS) in Stage IV breast cancer patients who complete a vaccination series with a HER2 CTL peptide -based vaccine while receiving m aintenance trastuzumab. Study Design This will be a single arm phase I -II single institution clinical trial in patients with HER2 overexpressing Stage IV breast and ovarian cancer who are on maintenance trastuzumab alone after being treated with chemothe rapy and trastuzumab or trastuzumab alone to NED or stable disease. Patients will receive a monthly vaccination for 6 months with a HER2 CTL peptide -based vaccine. Number of Patients Twenty subjects will be enrolled. This will provide statistically adequate numbers of subjects for gathering (1) safety data and (2) immunologic response data. Outcome Measures Primary Endpoints: 1. Safety will be assessed using NCI common toxicity criteria. 2. Immune response will be defined by cytokine flow cytometry (CFC). Specifically, a positive immune response will be defined as a post-vaccination HER2 antigen specific CD8 or CD4 precursor frequency measured by CFC of < 1:20,000. For subjects who have measurable precursors by CFC at baseline, a positive response will be defined as a 2 -fold increase in either T cell subset after vaccination. HLA -A2 MHC tetramer analysis will be used to demonstrate the specificity of the T cells for the HER2 HLA -A2 defined epitopes. IFN - gamma secreting PBMC precursor frequency will also be measured by ELIspot in order to determine the development of lower precursor frequencies not detected by CFC. ELIspot measurements will not define response.