Patient description: The patient is a 45-year-old postmenopausal woman with cytologically confirmed breast cancer. A core biopsy revealed a 3 cm invasive ductal breast carcinoma in the left upper outer quadrant. The tumor is HER2-positive and ER/PR negative. Axillary sampling revealed 5 positive lymph nodes. CXR was remarkable for metastatic lesions. The patient is using multivitamins and iron supplements. She does not smoke or consume alcohol. She is not sexually active and has no children. She is a candidate for tumor resection and agrees to do so prior to chemotherapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Breast Cancer Triple Negative Breast Cancer HER2+ Breast Cancer Hormone Receptor Negative Breast Cancer Metastatic Breast Cancer Patients must have histologically or cytologically confirmed metastatic HER2+ breast cancer. HER2 positive or amplified breast cancer is defined as IHC 3+ or FISH average HER2 copy number greater than or equal to 6 signals per cell or HER2/CEP17 greater than or equal to 2.0. HER2 testing must have been performed in a laboratory accredited by the College of American Pathology (CAP) or another accrediting entity Patients must have hormone receptor negative, HER2+ breast cancer. Hormone receptor negative is defined as estrogen receptor < 10% by IHC and progesterone receptor < 10% by IHC Patients must have measurable disease, per 1.1 Patients must have at least one lesion deemed safe to biopsy and be willing to undergo up to three biopsies while on trial Patients must have received front-line treatment for metastatic disease with a taxane, trastuzumab and pertuzumab (THP; docetaxel or paclitaxel allowed) and progressed on treatment or were intolerant to treatment. Patients must have received at least one prior therapy in the metastatic setting. Prior T-DM1 therapy is allowed Female or male greater than or equal to 18 years ECOG performance status 0 or 1 Patients must have adequate bone marrow function as defined below absolute neutrophil count greater than or equal to 1,500/mcL (> 1.5X 10(6)/L) platelets greater than or equal to 100,000/mcL  Patients who have received chemotherapy, including herceptin and/or pertuzumab in the prior 3 weeks (6 weeks for nitrosoureas or mitomycin); other investigational agents or a PD-1/L1 agent within 4 weeks prior to study enrollment Patients who have received radiotherapy within 4 weeks prior to study entry Patients with active brain metastases or leptomeningeal metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events. However, patients with treated brain metastases are eligible if there is no magnetic resonance imaging (MRI) evidence of progression for 6 weeks after treatment is complete (no radiotherapy within 6 weeks) and within 28 days prior to the first dose of trial drug or asymptomatic brain metastasis. Patients requiring immunosuppressive doses of systemic corticosteroids (> 10mg/day prednisone equivalent) for palliation are excluded Patients with a history of another invasive malignancy less than or equal to 3 years prior to enrollment (patients with non-melanoma skin cancers, carcinoma in situ of the breast or cervix are eligible) History of allergic reactions attributed to compounds of similar chemical or biologic composition to agents used in study. For example, reaction to prior vaccination with vaccinia virus or known hypersensitivity reaction to fully humanized monoclonal antibodies (Grade greater than or equal to 3 NCI-CTCAEv5) Uncontrolled intercurrent illness including, but not limited to, ongoing active infection that requires systemic treatment with ongoing antibiotics (eligible if can stop antibiotics on day of enrollment), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that in the opinion of the primary investigator would prohibit the patient from complying with study requirements Known history of a gastrointestinal illness that in the investigator s opinion would prevent the absorption of entinostat, which is an oral agent. (Arm 3 ONLY) Patients with bone metastases who have initiated denosumab or a bisphosphonate therapy within 28 days prior to or after Cycle 1 Day 1. Continuation of prior therapy is allowed Patients with inherited bleeding disorders, a history of bleeding diathesis such as vWF deficiency or recent (within 3 months prior to enrollment) clinically significant bleeding events that, in the judgment of the investigator, would interfere with patient s ability to carry out the treatment program Patients should have no evidence of being immunocompromised as listed below