This randomized phase II trial studies how well carboplatin and paclitaxel with or without panitumumab work in treating patients with invasive triple negative breast cancer. Drugs used in the chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping the them from dividing, or by stopping them from spreading. Monoclonal antibodies, such as panitumumab, may interfere with the ability of tumor cells to grow and spread. Giving carboplatin and paclitaxel with or without panitumumab before surgery may make the tumor smaller and reduce the amount of normal tissue that needs to be removed.

PRIMARY OBJECTIVES:

I. To determine the pathologic complete response (pCR) rate in patients with primary triple-receptor negative (estrogen receptor [ER]-negative, progesterone receptor [PgR]-negative, and human epidermal growth factor receptor 2 [HER2]-negative) inflammatory breast cancer (TN-IBC) by using a combination of panitumumab, carboplatin, and paclitaxel (PaCT) in comparison with carboplatin and paclitaxel (CT) followed by adriamycin and cyclophosphamide (AC) in a neoadjuvant setting.

SECONDARY OBJECTIVES:

I. To determine the disease-free survival (DFS) rates produced by either arm of trial combination treatment.

II. To determine the overall survival (OS) rates produced by either arm of trial combination treatment.

III. To determine the safety and tolerability of both arms of trial combination treatment.

EXPLORATORY OBJECTIVES:

I. To determine whether the pCR rate positively correlates with reduced nodal expression status.

II. To determine whether the pCR rate inversely correlates with arginine methylation status of epidermal growth factor receptor (EGFR).

III. To identify molecular biomarkers predictive of the pCR rate by analysis of multiplexed immunohistochemical (IHC) staining.

IV. To identify molecular biomarkers predictive of the pCR rate by genomic and proteomic analysis.

V. To determine whether the inhibition of the EGFR pathway downregulates the COX-2 pathway and mesenchymal marker.

OUTLINE: Patients are randomized into 1 of 2 groups.

GROUP A: Patients receive panitumumab intravenously (IV) over 1 hour on day 1 of cycle 0 and over 30 minutes on days 1, 8, and 15 of cycles 1-4. Patients also receive paclitaxel IV over 1-3 hours on days 1, 8, and 15 of cycles 1-4, and carboplatin IV over 30 minutes on day 1 of cycles 1-4. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.

GROUP B: Patients receive paclitaxel, carboplatin, doxorubicin, and cyclophosphamide as in Group A. Treatment repeats every 21 days for up to 8 cycles in the absence of disease progression or unexpected toxicity.

After completion of study treatment, patients are followed up at 1 month and then annually for at least 5 years.

Inclusion Criteria:

• Patients must have histological confirmation of breast carcinoma

• Patients must have invasive breast cancer (IBC), confirmed according to international consensus criteria:

  • Onset: Rapid onset of breast erythema, edema, and/or peau d'orange, and/or warm breast, with or without an underlying breast mass
  • Duration: History of such findings no more than 6 months
  • Extent: Erythema occupying at least 1/3 of whole breast
  • Pathology: Pathologic confirmation of invasive carcinoma

• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

• Patients must have negative HER2 expression on immunohistochemistry (IHC) (defined as 0 or 1+) or fluorescence in situ hybridization (FISH) analysis; if HER2 is 2+, negative HER2 expression must be confirmed by FISH (HER2/cep17 ration < 2, and/or copy number less than 6); ER and PgR expression should be less than 10%

• Patients have left ventricular ejection fraction (LVEF) >= 50% by multigated acquisition scan (MUGA) or echocardiogram before study randomization

• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L

• Platelet count >= 100 x 10^9/L

• Hemoglobin >= 9.0 g/dL

• Aspartate aminotransferase (AST) =< 3.0 x upper limit of normal (ULN)

• Alanine aminotransferase (ALT) =< 3.0 x ULN

• Alkaline phosphatase (ALP) =< 2.5 x ULN

• Total bilirubin =< 1.5 x ULN

• Creatinine (Cr) =< 1.5 mg/dL x ULN

• Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockroft-Gault

• Patients have the ability and willingness to sign written informed consent

• Patients of childbearing potential (women who are postmenopausal for < 1 year, not surgically sterilized, or not abstinent), have a negative urine pregnancy test, and agree to the consistent and correct use of one of the following acceptable methods of birth control: male partner who is sterile before the female subject's entry into the study and is the sole sexual partner for that female subject; intrauterine device, oral contraception, or barrier methods, including diaphragm or condom with a spermicide

Exclusion Criteria:

• Stage IV disease, if the metastatic sites are not amendable for local therapy (i.e. radiation and/or surgery), and are not candidates for breast surgery will not be eligible
• History of radiotherapy for current breast cancer diagnosis
• History of recent malignancies < 5 years (except for cured non-melanomatous skin cancer or cured cervical carcinoma in situ)
• Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection
• History of extensive interstitial lung disease, e.g., pneumonitis or pulmonary fibrosis or any evidence of extensive interstitial lung disease on baseline chest computed tomography (CT) scan
• Other known other significant medical or psychiatric condition that would make assessment of toxicity or efficacy difficult
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with a peripheral neuropathy > grade 1
• Patients with a history of New York Heart Association class 3 or 4 heart failure, or history of myocardial infarction, unstable angina, or cerebrovascular accident (CVA) within 6 months of protocol registration
• Patients have a history of prior therapy with carboplatin
• Patients have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2
• Patients have had prior radiotherapy for primary breast carcinoma or axillary lymph nodes
• Patients have history of diagnosed interstitial lung disease