This phase II trial studies how well panitumumab, carboplatin and paclitaxel work in treating patients with newly diagnosed triple negative breast cancer that is limited to the breast and possibly to the nearby lymph nodes (locally advanced). This treatment study is linked to NCI-2015-00191 protocol, which uses a baseline biopsy to determine the neoadjuvant therapy that matches the sub-type of triple negative breast cancer (TNBC). Immunotherapy with panitumumab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Drugs used in chemotherapy, such as carboplatin and paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving panitumumab, carboplatin and paclitaxel before surgery may be an effective treatment for breast cancer by making the tumor smaller and reducing the amount of normal tissue that needs to be removed.

PRIMARY OBJECTIVE:

I. To evaluate the pathologic complete response (pCR), residual cancer burden (RCB)-0 and RCB-I rates of patients with localized TNBC who were treated with panitumumab, carboplatin and paclitaxel (PaCT) in the neoadjuvant setting.

SECONDARY OBJECTIVES:

I. To estimate progression free survival (PFS) distribution of localized TNBC patients who were non-responders to initial anthracycline and cyclophosphamide chemotherapy, and who were treated with the PaCT regimen in the neoadjuvant setting.

II. Determine changes of epidermal growth factor receptor (EGFR) downstream biomarkers one week after 1 dose of panitumumab.

III. Determine response rate after 4 cycles of PaCT using radiographic imaging. IV. Correlate pathologic response with EGFR expression as measured by immunohistochemistry (IHC).

V. Determine toxicity associated to 4 cycles of PaCT in the neoadjuvant setting.

VI. Compare pathologic response to 4 cycles of PaCT in EGFR overexpressing tumors versus (vs.) non-EGFR overexpressing tumors.

VII. Compare pathologic response in tumors to 4 cycles of PaCT vs. 12 weeks of weekly paclitaxel (using data collected in conjunction with protocol 2014-0185).

EXPLORATORY OBJECTIVES:

I. Determine the correlation between EGFR expression by IHC and the presence of enhanced EGFR gene signatures at the time of initial tumor biopsy prior to neoadjuvant setting (NACT) (using gene expression data obtained from the protocol 2014-0185).

II. Determine rates of pCR in patients with EGFR overexpressed tumors identified by gene signatures (using gene expression data obtained from protocol 2014-0185) and compare to pCR rates in non-EGFR overexpressed tumors.

III. Determine the correlation between EGFR expression by IHC and the changes of EGFR downstream changes induced in surgery sample after completion of PaCT regimen.

IV. Determine the change in programmed cell death ligand 1 (PD-L1) glycosylation induced by panitumumab, and correlation with efficacy.

V. Determine the change after treatment in blood-based markers, if any, and use these to predict a response to panitumumab treatment.

OUTLINE:

Patients receive panitumumab intravenously (IV) over 30 minutes and paclitaxel IV over 30 minutes on days 1, 8, and 15. Patients also receive carboplatin IV over 30 minutes on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3-4 months.

Inclusion Criteria:

• Patients must have an intact evaluable primary tumor or biopsy proven axillary node involvement with at least 1.0 centimeter (cm) smallest dimension based on imaging after neoadjuvant anthracycline-based chemotherapy and prior to initiation of neoadjuvant chemotherapy under this protocol; baseline measurements and evaluations must be obtained within 4 weeks of registration to the study; all areas of disease should be recorded in order to assess response and uniformity of response to therapy
• Triple-negative breast cancer defined as estrogen receptor (ER) < 10%; progesterone receptor (PR) < 10% by immunohistochemistry (IHC) and human epidermal growth factor receptor 2 (HER2) 0-1 positive (+) by IHC or 2+, fluorescence in situ hybridization (FISH) < 2, gene copy number < 4
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Patients must have received at least one dose of an anthracycline based neoadjuvant regimen; patients are eligible if therapy was discontinued due to disease progression or therapy intolerance
• Baseline multi-gated acquisition (MUGA) or echocardiogram showing left ventricular ejection fraction (LVEF) >= 50% within 6 weeks prior to initiation of neoadjuvant chemotherapy
• Serum creatinine =< 1.5 mg/dl
• Creatinine clearance (CrCl) >= 50 mL/min calculated by the Cockcroft-Gault method
• Absolute neutrophil count (ANC) >= 1500/mm^3
• Platelets >= 100,000/mm^3
• Hemoglobin >= 9.0 g/dL
• Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) < 3.0 x upper limit of normal
• Alkaline phosphatase (Alp) =< 2.5 x upper limit of normal (ULN)
• Total bilirubin =< 1.5 x ULN
• Signed informed consent

Exclusion Criteria:

• Patient is unwilling or unable to sign and date the Institutional Review Board (IRB) approved informed consent
• Patients with less than a 1.0 cm measurable residual disease after neoadjuvant anthracycline based chemotherapy
• Women that are pregnant or lactating
• Patients with a history of prior malignancy within 5 years of study entry with the exception of curatively treated non-melanomatous skin cancer or carcinoma in situ of the cervix or breast
• Patients with a history of stage IV or metastatic disease
• Any serious medical illness, other than that treated by this study, which would limit survival to less than 1 month or psychiatric illness which would limit informed consent
• Known positive test(s) for human immunodeficiency virus infection, hepatitis C virus, acute or chronic active hepatitis B infection
• Patients with a peripheral neuropathy > grade 1
• Patients with a history of serious cardiac events defined as: 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 with a history of PR prolongation or atrioventricular (AV) block
• Patients with a history of prior therapy with paclitaxel and/or carboplatin
• Patients who have received a cumulative dose of doxorubicin of greater than 360 mg/m^2 or epirubicin of greater than 640 mg/m^2
• Patients who concurrently use hormonal therapy and/or concurrent radiation therapy
• Patients who had prior radiation therapy of the primary breast carcinoma or axillary lymph nodes
• Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, must use highly effective methods of contraception during the study and 8 weeks after; highly effective contraception methods include combination of any two of the following: placement of an intrauterine device (IUD) or intrauterine system (IUS), barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/ vaginal suppository, total abstinence or male/female sterilization; women are considered post-menopausal and not of child-bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks prior to treatment; in the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of child-bearing potential
• Male patients whose sexual partner(s) are WOCBP who are not willing to use adequate contraception, during the study and for 8 weeks after the end of treatment
• Negative serum or urine pregnancy test for women within 72 hours of receiving the first dose of the study medication for women of childbearing potential