Carboplatin and Paclitaxel Albumin-Stabilized Nanoparticle Formulation Before Surgery in Treating Patients With Locally Advanced or Inflammatory Triple Negative Breast Cancer

PRIMARY OBJECTIVES:

I. To test the hypothesis that carboplatin + nab-paclitaxel (paclitaxel albumin-stabilized
nanoparticle formulation) therapy will demonstrate a promising neoadjuvant pathologic
complete response (pCR) rate for eligible patients.

II. To test the hypothesis that carboplatin + nab-paclitaxel therapy will demonstrate a
promising Symmans 0-1 pathological response rate for eligible patients.

SECONDARY OBJECTIVES:

I To evaluate the overall survival and event-free survival of eligible patients treated with
carboplatin + nab-paclitaxel neoadjuvant chemotherapy.

II. To evaluate the toxicities and tolerance of carboplatin + nab-paclitaxel therapy in this
patient population.

III. To evaluate the role of laboratory correlates in response, toxicity and survival
endpoints.

IV. To procure tissue and perform analysis of gene and protein expression profiles of
pre-treatment primary tumor (estimated success rate: 80%) and residual tumors (25%) and lymph
nodes including the study of tumor niche (50%), studying sequential assessment of cellular
characteristics and gene and protein expression profiles.

V. To identify specific mutations in tumor deoxyribonucleic acid (DNA) in comparison to
adjacent tissue and germ line DNA procured prior to, during, and subsequent to neoadjuvant
chemotherapy, and to detect/measure, as feasible, the presence of such mutations in
fragmented circulating DNA from plasma, and to correlate these mutations with the
presence/characteristics of circulating tumor cells in order to identify prognostic and
predictive indicators of persisting/relapsed disease and targets for therapy.

VI. To assess ribonucleic acid (RNA) (using Mammaprint/Blueprint and 44,000 Agilent platform
gene array), (micro) miRNA and exosome and protein profiles in tumor, adjacent tissue and
plasma prior to, during, and at completion of neoadjuvant chemotherapy in order to establish
prognostic and predictive indicators of outcome, markers of persistent/relapsed disease, and
targets for therapy.

VII. To analyze tumor DNA and genomic DNA from plasma by microarray and reverse transcriptase
(RT)-polymerase chain reaction (PCR) analysis to assess copy numbers/single nucleotide
polymorphisms (SNP)/genomic polymorphisms in genes for the purposes of establishing
prognostic and predictive indicators of outcomes; markers of persistence/relapse disease,
drug resistance, and drug metabolism; and targets of therapy.

VIII. To assess the prognostic and predictive value of conventional pathological features
(stage, estrogen and progesterone receptor and human epidermal growth factor receptor [HER-2]
status, presence of lymphovascular invasion, high grade tumor status) in comparison to such
values derived from the molecular approaches.

IX. To procure tumor from the primary and definitive surgical specimen for the purpose of
establishing breast cancer stem cell lines.

X. To procure blood samples for the purpose of identifying and characterizing circulating
tumor cells.

OUTLINE: Patients receive carboplatin intravenously (IV) over 30 minutes on day 1 and
paclitaxel albumin-stabilized nanoparticle formulation IV over 30 minutes once weekly.
Treatment repeats every 28 days for 4 courses in the absence of disease progression or
unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for 4 years and
then every 6 months for 1 year and then periodically thereafter.

Inclusion Criteria:

- Patients must be diagnosed with locally advanced (T2 and higher with or without lymph
node involvement), and/or inflammatory triple negative breast cancer

- Women of child-bearing potential and men must agree to use adequate contraception
(hormonal or barrier method of birth control or abstinence) prior to study entry and
for six months following duration of study participation; should a woman become
pregnant or suspect that she is pregnant while participating on the trial, she should
inform her treating physician immediately

- Tumor negative for expression of hormone receptors (< 10%) and not over-expressing
HER2 by immunohistochemistry (IHC) (0-1), or in case of IHC of 2, negative by
fluorescence in situ hybridization (FISH) or by alternative gene testing

- Bilirubin =< 1.5 mg/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2 x upper limit
of normal

- Alkaline phosphatase =< 2 x upper limit of normal

- Platelets >= 100,000 cells/mm^3

- Hemoglobin > 9.0 g/dL

- Absolute neutrophil count (ANC) >= 1,500 cells/mm^3

- Creatinine =< 1.5 mg/dL is recommended; however, institutional norms are acceptable

- Left ventricular ejection fraction > 50%

- Women of childbearing potential and sexually active males must use an effective
contraception method during treatment and for three months after completing treatment

- Negative serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test
screening for patients of childbearing potential

- All subjects must have the ability to understand and the willingness to sign a written
informed consent

- No prior therapies are allowed for the treatment of the newly diagnosed breast cancer;
patients with a prior diagnosis of malignancy treated >= 5 years ago are eligible,
provided that they have not received prior taxanes or carboplatin as part of their
prior treatment regimen, and that they meet all eligibility criteria

Exclusion Criteria:

- Known active hepatitis B or C

- Known active human immunodeficiency virus (HIV)

- Prior breast cancer or other invasive malignancy treated within 5 years

- Pregnancy

- Neuropathy > grade 1

- Any other intercurrent medical/psychological problem deemed exclusionary by the
treating physician or investigators/primary investigator (PI)

- Subjects will be excluded who, in the opinion of the investigator, may not be able to
comply with the safety monitoring requirements of the study