Azacitidine and Entinostat in Treating Patients With Advanced Breast Cancer

Inclusion Criteria

• •Patient must have histologically or cytologically confirmed adenocarcinoma of the breast triple-negative (ER-, progesterone receptor \[PR\]-, human epidermal growth factor receptor 2 \[HER2\]-) or hormone positive/ HER2-, with evidence of locally advanced and inoperable or metastatic disease (American Joint Committee on Cancer \[AJCC\] Stage IV)
• •* NOTE: Triple-negative patients will be defined per American Society of Clinical Oncology-College of American Pathologists (ASCO-CAP) Guidelines; these guidelines state that ER and PR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls
• •* A patient who has a change in receptor status (e.g., PR negative to positive) may be stratified as triple negative or hormone positive, contrary to the most recent receptor testing, for the purposes of the study based upon the clinical course at the discretion of the Study Chair; for HER2 assessment, a negative result is an immuno-histochemistry staining of 0 or 1+, a fluorescence in situ hybridization (FISH) result of less than 4.0 HER2 gene copies per nucleus, or a FISH ratio of less than 1.8
• •Patients with triple negative disease must have progressed through at least 1 prior chemotherapy regimen (administered in the adjuvant or metastatic setting); hormone receptor-positive patients must have progressed through two lines of hormonal therapy (administered in the adjuvant or metastatic setting), unless otherwise eligible as per below, and at least 1 prior chemotherapy regimen (administered in the adjuvant or metastatic setting) with no known curative options available
• •In patients with metastatic disease in the liver, liver disease burden is limited to no more than 30% of total liver volume as assessed by local review
• •Patients must have measurable disease
• •Life expectancy of \>= 12 weeks
• •Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• •Hemoglobin (HgB) \>= 9.0 g/dL
• •Absolute neutrophil count (ANC) \>= 1,500/mcL
• •Platelet count \>= 100,000/mcL
• •Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN); an exception to this may be allowed for participants with Gilbert's syndrome with documented approval by the Protocol Chair
• •Serum glutamic oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) =\< 3 x ULN
• •Creatinine =\< institutional ULN or creatinine clearance \>= 60 mL/min using the Modified Cockcroft-Gault formula
• •Negative (serum or urine) pregnancy test done =\< 7 days prior to registration, for women of childbearing potential only
• •Patient must have an accessible tumor lesion from which a biopsy specimen can be obtained; NOTE: if baseline biopsy is attempted and is unsuccessful (eg, patient intolerance, inadequate tissue), the patient will still be considered eligible for the study
• •Ability to understand and the willingness to sign a written informed consent document
• •Willingness to provide tissue and blood samples for mandatory translational research
• •Willingness to return to the enrolling institution for follow-up