Azacitidine in Treating Patients With Triple Negative Stage I-IV Invasive Breast Cancer That Can Be Removed By Surgery

PRIMARY OBJECTIVES: I. To evaluate the ability of deoxyribonucleic acid (DNA) methylation
inhibition using 5-azacitidine to induce expression of the estrogen receptor (ER) and
progesterone receptor (PR) genes in solid human triple negative invasive breast cancer.
SECONDARY OBJECTIVES: I. To determine the effect of systemic 5-azacitidine therapy on the
expression of other methylated genes in triple negative invasive breast cancer using an
Illumina GoldenGate array. OUTLINE: Patients receive azacitidine intravenously (IV) over
10-40 minutes 5 days a week for 2 weeks in the absence of disease progression or
unacceptable toxicity. Patients undergo definitive breast surgery within 12 days of the last
dose of azacitidine.

Inclusion Criteria:

- Resectable tumor measuring 2 cm or more

- Histologically documented triple negative invasive breast cancer characterized by 0%
Immunohistochemistry (IHC) nuclear staining for ER-alpha, 0% IHC nuclear staining for
PR-alpha, and no amplification of HER2/neu by fluorescence in situ hybridization
(FISH); standard IHC assays for ER and PR use antibodies to ER-alpha and PR-alpha and
PR-beta

- Southwest Oncology Group (SWOG) performance status of less than or equal to 1

- Absolute neutrophil count (ANC) >= 1500/μL

- Hemoglobin (Hgb) >= 9 g/dL

- Platelets >= 100,000/uL

- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and
alanine aminotransferase (ALT)/serum glutamic pyruvate transaminase (SGPT) =< 2.5 x
upper limit normal (ULN) or =< 5.0 x ULN in patients with liver metastases

- Creatinine =< 2.0 mg/dL Or Calculated Creatinine Clearance >= 50 ml/min

- Albumin >= 3 g/dL

- Potassium >= lower limit normal (LLN)

- Phosphorous >= LLN

- Calcium >= LLN

- Magnesium > LLN

- Women of childbearing potential must have a negative serum or urine pregnancy test
performed within 7 days prior to start of treatment

- Accessible for treatment and follow-up

- Written informed consent prior to study entry

Exclusion Criteria:

- HER2/neu amplification by FISH

- Concurrent neoadjuvant treatment with chemotherapy, endocrine therapy, or
radiotherapy

- Known hypersensitivity to azacitidine or mannitol

- Preexisting hepatic impairment or renal impairment

- Intent to receive additional neoadjuvant therapy prior to surgery

- Concurrent use of an histone deacetylase (HDAC) inhibitor or hydralazine

- Known diagnosis of human immunodeficiency virus (HIV) infection

- Major surgery < 4 weeks prior to starting study drug

- Pregnant or breastfeeding or female of reproductive potential not using an effective
method of birth control

- Other concurrent severe, uncontrolled infection or intercurrent illness, including
but not limited to ongoing or active infection or psychiatric illness/social
situations that would limit compliance with study requirements

- Prior antiestrogens (selective estrogen receptor modulator [SERM] or aromatase
inhibitors) within 6 months of study entry

- Underlying medical, psychiatric or social conditions that would preclude patient from
receiving treatment