Inclusion Criteria

Inclusion Criteria

- Signed and dated institutional review board (IRB)-approved consent form

- Women of reproductive potential must agree to use an effective nonhormonal method of
contraception during therapy

- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 and/or
Karnofsky PS of >= 70%

- Diagnosis of invasive adenocarcinoma of the breast made by core needle biopsy

- Palpable primary breast tumor measuring >= 2.0 cm on physical exam or imaging

- Patients with stage II-IIIA breast cancer that is HER2-negative by
immunohistochemistry (IHC) (0-2+) or fluorescence in situ hybridization (FISH)
(HER2/chromosome enumeration probe [CEP]17 amplification ratio < 2.2) for whom
definitive surgical treatment after "third generation" neoadjuvant chemoT is planned;
Patients with HER2 (3+) cancer by IHC that also demonstrate a FISH ratio <2.2 are
also eligible. Estrogen receptor (ER) or progesterone receptor (PR) status can be
positive or negative; the receptor status needs to be recorded

- Patients may have lymph node positive or negative disease, as long as they have
clinical stage II or IIIA breast cancer; patients may have the lymph nodes assessed
by any method deemed appropriate by the treating physicians, including
pre-neoadjuvant therapy sentinel lymph node biopsy

- Patients must discontinue sex hormone therapy prior to registration, e.g. birth
control pills, hormonal replacement therapy

- Absolute neutrophil count (ANC) must be >= 1200/mm^3

- Platelet count must be >= 100,000/mm^3

- Hemoglobin must be >= 9.0 mg/dL

- Total bilirubin must be =< the upper limit of normal (ULN) for the lab unless the
patient has a grade 1 bilirubin elevation (> ULN to 1.5 x ULN) resulting from
Gilbert's disease or similar syndrome due to slow conjugation of bilirubin; and

- Alkaline phosphatase must be =< 2.5 x ULN for the lab

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) must be =< 1.5 x ULN
for the lab

- Alkaline phosphatase and AST/ALT may not both be > the ULN; for example, if the
alkaline phosphatase is > the ULN but =< 2.5 x ULN, then the AST/ALT must be =< the
ULN; if the AST/ALT is > the ULN but =< 1.5 x ULN, then the alkaline phosphatase must
be =< ULN

- Patients with either skeletal pain or alkaline phosphatase that is > ULN must have a
bone scan showing they do not have metastatic disease; suspicious findings on bone
scan must be confirmed as benign by x-ray, magnetic resonance imaging (MRI), or
biopsy

- Patients with AST/ALT or alkaline phosphatase > ULN must have liver imaging that does
not demonstrate metastatic disease

- Patients with AST/ALT > ULN must have negative hepatitis studies

- Patients with stage II disease and clinical suspicion for metastatic disease based on
reported symptoms, physical examination findings, or laboratory abnormalities must
have staging studies demonstrating no evidence of metastatic disease (with exception
of axillary lymph nodes or mammary nodes); patients with stage IIIA disease must have
staging studies demonstrating no evidence of metastatic disease (with exception of
axillary lymph nodes or mammary nodes), even if asymptomatic with normal physical
examination and laboratory values; such staging studies must include: chest imaging
(chest X-ray, computed tomography [CT], or MRI), abdominal/pelvis imaging (CT or
MRI), and bone imaging (bone scan or positron emission tomography [PET]-scan);
abnormalities that are indeterminate and too small to biopsy should be followed with
further imaging, as appropriate, but do not exclude patients from the study;
abnormalities that are suspicious and large enough to biopsy exclude patients from
the study, unless a biopsy is performed and is negative for metastatic disease

- Serum creatinine =< 1.5 x ULN for the lab

- Pre-entry core biopsy with sufficient material for correlative studies

- Left Ventricular Ejection Fraction (LVEF) >= 50 % (by multigated acquisition scan
[MUGA] or echocardiography)

Exclusion Criteria

- Tumor determined to be HER2-positive by immunohistochemistry (3+) or by fluorescent
in situ hybridization (HER2/CEP17 amplification ratio >= 2.0)

- Tumors clinically staged as T4 or N3

- Definitive evidence of metastatic disease with exception of axillary lymph nodes or
mammary nodes

- Synchronous bilateral breast cancer (invasive or ducal carcinoma in situ [DCIS])

- Treatment including radiation therapy, chemoT, biotherapy, and/or hormonal therapy
for the currently diagnosed breast cancer prior to study entry

- Any sex hormonal therapy, e.g., birth control pills, ovarian hormonal replacement
therapy, etc. (These patients are eligible if this therapy is discontinued 1 week
prior to registration)

- Prior history of invasive breast cancer (Patients with a history of DCIS or lobular
carcinoma in situ [LCIS] are eligible)

- Prior therapy with anthracyclines for any malignancy

- Other malignancies unless the patient is considered to be disease-free for 5 or more
years prior to randomization and is deemed by the physician to be at low risk for
recurrence; patients with the following cancers are eligible if diagnosed and treated
within the past 5 years: carcinoma in situ of the cervix, carcinoma in situ of the
colon, melanoma in situ, and basal cell or squamous cell carcinoma of the skin

- Known cardiac disease that would preclude the use of anthracyclines; this includes:

- Angina pectoris that requires the use of anti-anginal medication

- History of documented congestive heart failure

- Serious cardiac arrhythmia requiring medication

- Severe conduction abnormality

- Valvular disease with documented cardiac function compromise; and

- Uncontrolled hypertension defined as blood pressure (BP) that is consistently >
150/90 on antihypertensive therapy at the time of registration (Patients with
hypertension that is well controlled on medication are eligible)

- History of myocardial infarction (MI) documented by elevated cardiac enzymes with
persistent regional wall motion abnormality on assessment of left ventricular (LV)
function (Patients with history of MI must have an echo instead of/in addition to a
MUGA to evaluate LV wall motion)

- Symptomatic peripheral vascular disease

- Sensory/motor neuropathy >= grade 2, as defined by the National Cancer Institute
(NCI)'s Common Terminology Criteria for Adverse Events Version 4.0 (CTCAE v4.0)

- Other non-malignant systemic disease (cardiovascular, renal, hepatic, etc.) that
would preclude treatment with any of the treatment regimens or would prevent required
follow-up

- Chronic ongoing steroid use at the time of registration for any condition (such as
asthma, rheumatoid arthritis, etc)

- Administration of any investigational agents within 30 days before study entry

- Pregnancy or lactation at the time of registration

- Psychiatric or addictive disorders or other conditions that in the opinion of the
investigators would preclude the patient from complying with the study protocol.

Minor changes from these guidelines will be allowed at the discretion of the research team
under special circumstances. The reasons for exceptions will be documented