Neoadjuvant DPX-Survivac Aromatase Inhibition, Radiotherapy or Cyclophosphamide in HR+HER2- Breast Cancer

Women with hormone receptor positive, HER2-negative (HR+/HER2-) breast cancer with large tumors or positive lymph nodes have low response rates with neoadjuvant chemotherapy. Survivin is overexpressed in HR+HER2- breast cancer. Increasing tumor-specific Th1 immunity by administration of DPX-Survivac may alter the immune environment of these tumors. Radiation is a standard component of breast cancer therapy causing a reduction in local recurrences and improved breast cancer specific survival. Low dose cyclophosphamide can deplete regulatory T-cells without altering levels of effector T-cells. The investigators predict that combining a vaccine targeting Survivin, overexpressed in HR+HER2- tumors, with other immune modulating therapies such as radiation or low dose cyclophosphamide can enhance the efficacy of DPX-Survivac. Primary Objective 1\) Safety of neoadjuvant aromatase inhibitor with: DPX-Survivac, DPX-Survivac plus radiation, or DPX-Survivac with cyclophosphamide in stage I to III HR+HER2- breast cancer Secondary Objectives 1. Immunogenicity of each arm, assessed by IFN-γ ELISPOT in PBMC. 2. Immunogenicity of each arm, assessed by GEO-Mx digital spatial profiler evaluation of FFPE tissue and TCRβ evaluation for surviving-specific T cells in the tumor. Exploratory Objectives 1. Evaluation of the % TIL in the biopsy specimen and at the time of surgery within/between arms 2. Evaluation of the Ki67 changes between the biopsy and at time of surgery within/between arms 3. Comparison of immunogenicity, TIL change, and Ki67 change across arms 4. Epitope spreading within/between arms 5. Evaluation of Triseq (germline, whole exome sequencing, and RNAseq) of the tumor immune environment within/between arms 6. Evaluation of immune environment using multi-parameter immunohistochemistry within/between arms 7. Evaluation by experimental MRI in arm that adds radiation 8. Evaluation of survivin-specific MHC-tetramer staining in PBMC