Cisplatin and Paclitaxel With or Without Everolimus in Treating Patients With Stage II or Stage III Breast Cancer

Eligibility criteria

-Maximum number of patients will include two-thirds of the patients in Arm 1 and one-third of the patients for Arm 2 (total of 145 patients). Estimated time for accrual with ~ 3 patients/month would be ~ 3.5 years.

Inclusion criteria

• Patients must provide informed written consent.
• Patient must be ≥ 18 years of age.
• ECOG performance status 0-1.
• Clinical stage II or stage III triple-negative (ER and/or PR no staining or weak staining in less than or equal to 10% cells by immunohistochemistry [IHC] and HER2-negative by Herceptest [0, 1+] or FISH) invasive mammary carcinoma, confirmed by histological analysis.
• Patients who have measurable* residual tumor at the primary site

*Measurable disease: any mass that can be reproducibly measured by physical examination, mammogram, and/or ultrasound and can be accurately measured in at least one dimension (longest diameter to be recorded) as 10 mm (1 cm), either in the breast or axillary lymph nodes.

• Available core biopsies from the time of diagnosis. Fresh tissue must be obtainable at baseline or fresh tissue biopsy prior to treatment initiation.
• Patients who will undergo surgical treatment with either segmental resection or total mastectomy.
• Patients must have adequate hematologic, hepatic, and renal function. All tests must be obtained less than 4 weeks from study entry. This includes:
• ANC >/=1500/mm3
• Platelet count >/=100,000/mm3
• Creatinine </=1.5X upper limits of normal
• Bilirubin, SGOT, SGPT </=1.5X upper limits of normal*
• for patients with Gilbert"s syndrome, direct bilirubin will be measured instead of total bilirubin.
• The patient must have not had anyprior chemotherapy for primary breast cancer.
• Patients with a prior history of contra-lateral breast cancer are eligible if they have no evidence of recurrence of their initial primary breast cancer within the last 5 years.
• Able to swallow and retain oral medication.
• Four days prior to biopsy procedures patients must be off medications that could increase risk of bleeding (i.e. ASA, NSAIDS, Coumadin, heparin products)
• Potential subjects must complete all screening assessments as outlined in the protocol.
• The pre-menopausal patient of childbearing potential must have had a negative pregnancy test and agreed to use birth control methods while participating in the study. Note: Women of childbearing potential and their male counterparts should use a barrier method of contraception during and for 3 months following protocol therapy.

Ineligibility Criteria

Exclusion Criteria

• Locally recurrent breast cancer.
• Pregnant or lactating women.
• Evidence of distant metastatic disease (i.e. lung, liver, bone, brain, etc.)
• Use of CYP3A4 modifiers (Appendix A)
• Serious medical illness that in the judgment of the treating physician places the patient at high risk of operative mortality.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel.
• History of other malignancy. Subjects who have been disease-free for 5 years, or subjects with a history of completely resected non-melanoma skin cancer or successfully treated in situ carcinomas are eligible.
• History of hepatitis B or hepatitis C. If patient is judged to be at risk for having had exposure to viral B or C hepatitis (i.e. illicit IV drug use, blood transfusion prior to 1990, body piercing, tattoos, etc.), appropriate testing should be performed (i.e. Hepatitis B surface antigen antibody, and Hepatitis C antibody)
• Active or uncontrolled infection requiring parenteral antibiotics.
• Dementia, altered mental status, or any psychiatric condition that would prohibit the understanding or rendering of informed consent.
• Symptomatic neuropathy (≥ grade 2).
• Concurrent anti-cancer therapy (chemotherapy, radiation therapy, surgery, immunotherapy, hormonal therapy, or any other biologic therapy) other than the ones specified in the protocol.
• Concurrent tre