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,  Triple Negative Breast Cancer Endometrial Cancer Hormone Receptor Positive, HER2 Negative Breast Cancer FOR 1 Patients must have histologically confirmed persistent or recurrent invasive metastatic hormone receptor positive, HER2 normal breast cancer for which standard curative measures do not exist or are no longer effective. Hormone receptor positive is defined as estrogen receptor (ER) positive greater than or equal to 10% by immunohistochemistry (IHC) and/or progesterone receptor (PR) positive greater than or equal to 10% by IHC.HER2 will be considered negative per ASCO-CAP guidelines (HER2 test result as negative if a single test (or both tests) performed show: 1) IHC 1+ as defined by incomplete membrane staining that is faint/barely perceptible and within >10% of the invasive tumor cells; 2) IHC 0 as defined by no staining observed or membrane staining that is incomplete and is faint/barely perceptible and within less than or equal to 10% of the invasive tumor cells; or 3) ISH negative based on: a) Single-probe average HER2 copy number <4.0 signals/cell or b) Dualprobe HER2/CEP17 ratio <2.0 with an average HER2 copy number <4.0 signals/cell)and HER2 testing must have been performed in a laboratory accredited by the College of American Pathologists (CAP) or another accrediting entity Patients must have measurable disease, per 1.1 Patients must have at least one lesion deemed safe to biopsy and be willing to undergo mandatory biopsies HR+BC patients must have received prior treatment with at least 2 lines of hormonal treatment (SERM, AI, or fulvestrant) and deemed ineligible for further hormonal therapy. Patients may have received prior chemotherapy and there is no limit to the number of prior chemotherapy Age greater than or equal to18 years ECOG performance status 0 or 1 Adequate renal function, defined as serum creatinine less than or equal to 1.5 X upper limit of normal (ULN), or measured creatinine clearance greater than or equal to 60 mL/min/1 Adequate hepatic function, defined as AST and ALT levels less than or equal to 3 X ULN and total bilirubin < 1.5 X ULN, unless known diagnosis of Gilbert's syndrome, where bilirubin less than or equal to 5 mg/dL will be permitted. Gilbert's syndrome will be defined as elevated unconjugated bilirubin, with conjugated (direct) bilirubin within the normal range and less than 20% of the total. Total bilirubin will be permitted up to 5 mg/dL, if patients have historical readings consistent with the definition of Gilbert's syndrome prior to entering study Adequate bone marrow function, defined as absolute neutrophil (ANC) greater than or equal to 1,500/mm^3 (greater than or equal to 1.5 X10^6/L), platelet count greater than or equal to 75,000/mm^3 (greater than or equal to 75 X10^6/L), and hemoglobin greater than or equal to 9 mg/dL (transfusion to obtain hemoglobin greater than or equal to 9 mg/dL within 24 hours prior to dosing is allowed)  FOR 1 Patients who have received chemotherapy in the previous 3 weeks (6 weeks for nitrosoureas or mitomycin); other investigational agents within 3 weeks or a PD1/PDL1 agent within 4 weeks prior to first dose of study enrollment Patients who have undergone radiotherapy within 4 weeks of first dose of study treatment Patients with a history of another invasive malignancy within the last 3 years Patients with symptomatic brain metastases or leptomeningeal involvement. Patients with asymptomatic or brain metastases that have been treated with radiation at least 4 weeks prior to first dose of study treatment are allowed History of allergic reactions attributed to compounds of similar chemical or biologic composition to imipridones or other agents used in study Patients with a mean QTcF interval of > 500 msec or receiving therapeutic agents known to prolong the QT interval Known history of cardiac arrhythmias including uncontrolled atrial fibrillation, tachyarrhythmias or bradycardia, history of congestive heart failure, or myocardial infarction or stroke in the previous 3 months will be excluded Known history of gastrointestinal illnesses that would preclude the absorption of ONC201, which is an oral agent Patients with bone metastases who have initiated denosumab or bisphosphonate therapy within 28 days prior to Cycle 1 Day 1