A Pilot and Phase II Study of Entinostat and Anastrozole/Tamoxifen in Women With Triple Negative Breast Cancer to Evaluate Biomarkers and Surrogates for Response

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the breast

- Unresected breast cancer amenable to surgery

- Clinical stage

- T1c, T2, or T3

- Any N

- M0 (no distant metastasis)

- Hormone insensitivity

- Evidence of hormone insensitivity (ER and PR negative) of primary tumor
tissue; ER negative is define as ER 0 or < 1% staining by
immunohistochemistry; PR negativity is defined as PR =< 10% staining by
immunohistochemistry

- HER2 negative in the primary tumor tissue by:

- Grade 0 or 1+ staining intensity (on a scale of 0 to 3) by IHC analysis

- Grade 2+ staining intensity by IHC with gene amplification on fluorescent
in situ hybridization (FISH) < 2.2

- Patients must have adequate tumor tissue sample prior to the enrolment available for
correlative studies as defined below:

- Core needle biopsy or incisional biopsy samples that can provide >= 3 unstained
sections of 5 micron thickness; fine needle aspiration (FNA) sample alone is not
sufficient except in the second cohort

- Additional core needle biopsy needs to be performed in the patients who agree to
participate in this study and do not have adequate tumor tissue sample

- Patients must have an accessible tumor lesion from which a fine needle aspirate
or preferably a core biopsy specimen can be obtained; patients with FNA only
samples are allowed in this cohort; ascites or pleural/pericardial effusion
alone is not sufficient

- Patients must be willing to provide consents for 2 research biopsies; however,
the pretreatment biopsy can be omitted in patients who have recent biopsy but
have not been started on breast cancer treatment within 12 weeks prior to the
registration and there is adequate tumor tissue sample

- Postmenopausal

- ECOG performance status 0-2

- WBC ≥ 2,500/mm³

- ANC ≥ 1,100/mm³

- Platelet count ≥ 100,000/mm³

- Hemoglobin ≥ 9.0 g/dL

- Total bilirubin normal

- AST and ALT ≤ 2.5 times upper limit of normal

- Creatinine normal OR creatinine clearance ≥ 60 mL/min

- No history of allergic reactions or hypersensitivity to compounds of similar chemical
or biologic composition to entinostat, benzamide, or anastrozole

- No medical conditions that, in the opinion of the investigator, puts the patient at
risk of potentially serious complications while on this study, including any of the
following:

- HIV infection

- Unstable angina

- Uncontrolled heart failure or hypertension

- Hyperlipidemia

- Diabetes mellitus

- Systemic infection

- No systemic malignancy within the past 3 years except adequately treated cervical
carcinoma in situ or basal/squamous cell carcinoma of the skin

- No other concurrent anticancer agents including approved luteinizing-hormone
releasing-hormone agonists (e.g., goserelin or leuprolide)

- No prior histone deacetylase inhibitors (HDACs)

- Prior valproic acid allowed provided patient has ≥ 30 days wash-out period

- No prior chemotherapy, radiotherapy, or endocrine therapy for the current breast
cancer

- Prior tamoxifen, raloxifene, or another agent for the prevention of breast
cancer allowed provided patient has discontinued treatment within the past 30
days prior to baseline study biopsy.

- No bisphosphonates initiated within 4 weeks of study start

- No other concurrent investigational agents

- No concurrent valproic acid, vorinostat, or other HDAC inhibitor

- No concurrent DNA methyltransferase inhibitors