PTX-200, Paclitaxel, Doxorubicin Hydrochloride, and Cyclophosphamide in Treating Patients With Stage IIB-IV Breast Cancer

• Phase I and expansion cohort: Patients must have histologically or cytologically confirmed adenocarcinoma of the breast associated with clinical stage: IV (see American Joint Committee on Cancer [AJCC] staging criteria, 7th edition) or stage IIB-IIIC (expansion cohort only)
• Phase II: Patients must have histologically or cytologically confirmed adenocarcinoma of the breast associated with the following clinical stage: IIB, IIIA, IIIB, or IIIC (see AJCC staging criteria, 7th edition); the tumor must be human epidermal growth factor receptor 2 (Her2)/neu negative (by DAKO HercepTest, fluorescence based in situ hybridization [FISH], or other approved assay)
• Phase I and expansion cohort: Up to two prior non-taxane chemotherapy regimens for metastatic disease are permitted for patients enrolled on the phase I portion of the trial; patients with HER2/neu positive breast cancer are not eligible; patients treated with prior anthracycline therapy as neoadjuvant, adjuvant, or metastatic therapy are not eligible unless the following conditions are met: (a) prior cumulative doxorubicin dose is =\< 240 mg/m\^2 (or epirubicin dose is =\< 400 mg/m\^2), and (b) left ventricular ejection fraction (LVEF) obtained at baseline is at least 50% (or >= 5% above lower institutional limits of normal whichever is higher); patients with estrogen receptor (ER)-positive disease are required to have relapse or progression on at least one line of endocrine therapy
• Phase II: No prior chemotherapy, irradiation, or definitive therapeutic surgery (e.g., mastectomy or lumpectomy or axillary dissection) for this malignancy; patients who have had a prior sentinel lymph node biopsy for this malignancy are eligible
• Patients who received tamoxifen or another selective estrogen receptor modulator (SERM) for prevention or treatment of breast cancer or for other indications (e.g., osteoporosis, prior ductal carcinoma in situ [DCIS]), or who receive aromatase inhibitors for prevention or treatment of breast cancer, are eligible; patients who are hormone-receptor positive and who have received other hormonal agents for the treatment of breast cancer (e.g., Fulvestrant) are also eligible; tamoxifen therapy or other hormonal agents should be discontinued at least 1 week before the patient is enrolled on this study
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Leukocytes >= 3,000/uL
• Absolute neutrophil count =\< 1,500/uL
• Platelets >= 100,000/uL
• Total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x institutional upper limit of normal
• Left ventricular ejection fraction (LVEF) within normal institutional limits
• Creatinine within normal institutional limits
• LVEF at or above institutional lower limits of normal (>= 50%), or at least 5% above lower limits of normal if prior anthracycline exposure (by echocardiogram or nuclear scan within 12 weeks of registration)
• Electrocardiogram (ECG) corrected QT (QTC) \< 450 msec
• Serum calcium within normal institutional limits
• Serum phosphorus within normal institutional limits
• Fasting glucose within normal limits
• Patients must be disease-free of prior invasive malignancies for >= 2 years with the exception of curatively-treated basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix (for phase II only); patients with the following prior or concurrent diagnoses are eligible: lobular carcinoma in situ, contralateral ductal carcinoma in situ, or contralateral invasive ductal and/or lobular cancer (and no prior adjuvant chemotherapy for previous breast malignancy)
• Women of childbearing potential must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

• Patients may not be receiving any other investigational agents during protocol therapy, or up to 30 days prior to beginning protocol therapy; there should be a least a 1-week interval between last dose of endocrine therapy and protocol therapy, and at least 3 weeks for the last dose of biologic therapy (eg, bevacizumab) or cytotoxic therapy (or 2 weeks for capecitabine or weekly paclitaxel, 6 weeks for mitomycin-C and nitrosoureas), and adequately recovered from adverse effects from prior therapy to meet all other eligibility criteria
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to PTX-200 or other agents used in the study (e.g., imidazoles, quinolones)
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, diabetes mellitus requiring therapy (insulin or oral hypoglycemic agents), congenital prolonged QT syndrome, requirement for a drug known to prolong the QT interval, a history of QT prolongation, a screening QTc >= 450 msec, hypertriglyceridemia requiring therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with PTX-200; these potential risks may also apply to other agents used in this study
• Human immunodeficiency virus (HIV)-positive patients receiving combination antiretroviral therapy are excluded from the study