T-DM1+Pertuzumab in Pre-OP Early-Stage HER2+ BRCA

This research study is studying a combination of drugs as a possible treatment for breast cancer that has tested positive for a protein called HER2. The names of the study interventions involved in this study are: * Trastuzumab emtansine (also called T-DM1) * Pertuzumab

This research study is a Phase II clinical trial. Phase II clinical trials test the safety and effectiveness of an investigational intervention to learn whether the intervention works in treating a specific disease. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has not approved T-DM1 for pre-operative use in breast cancer but it has been approved for other uses in breast cancer. The FDA has approved pertuzumab as a pre-operative treatment.

Inclusion Criteria: * Patients must have HER2-positive Stage II or III histologically confirmed invasive carcinoma of the breast. A minimum tumor size of 2 cm determined by physical exam or imaging is required. * HER-2 positive, confirmed by central testing (Clarient labs): IHC 3+ and/or FISH positive based on one of the three following criteria: * Single-probe average HER2 copy number≥6.0 signals/cell OR * Dual-probe HER2/CEP17 \<2.0 with an average HER2 copy number ≥6.0 signals/cell OR * Dual-probe HER2/CEP17 ratio ≥2.0 * ER/PR determination is required. * Bilateral breast cancers are allowed if both cancers are HER2-positive. * Patients with multifocal or multicentric disease are eligible as long as one area meets eligibility criteria. * Breast imaging should include the ipsilateral axilla. For subjects with a clinically negative axilla, a sentinel lymph node biopsy will be performed either before or after preoperative therapy at the discretion of the subject's physicians. For subjects with a clinically positive axilla, a needle aspiration, core biopsy or SLN procedure will be performed to determine the presence of metastatic disease in the lymph nodes. * Men and women (with any menopausal status) ≥ 18 years of age * ECOG performance status 0 or 1 * Required laboratory values: * ANC ≥1500/mm3 * Hemoglobin ≥ 9 g/dl * Platelets ≥100,000/mm3 * Serum creatinine \< 1.5 X ULN (institutional) * Total bilirubin ≤ 1.0 X ULN (institutional) For patients with Gilbert syndrome, the direct bilirubin should be within the institutional normal range. * AST and ALT ≤ 1.5x ULN (institutional) * Alkaline phosphatase ≤1.5x ULN (institutional) * Documentation of hepatitis B virus (HBV) and hepatitis C virus (HCV) serologies is required: this includes hepatitis B surface antigen (HBsAg) and/or total hepatitis B core antibody (HBcAb) in addition to HCV antibody testing. * Only for patients who test positive for hep B/C virus: PTT/INR \< ULN (institutional) * Left ventricular ejection fraction (LVEF) ≥ 55% * Premenopausal women must have a negative serum pregnancy test, including women who have had a tubal ligation and for women less than 12 months after the onset of menopause. * Women of childbearing potential and men with partners of childbearing potential must be willing to use one highly effective form of non-hormonal contraception or two effective forms of non-hormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment and for 7 months after the last dose of study treatment. * Potent CYP3A4 inhibitors, such as ketoconazole and erythromycin, should be avoided during the study treatment period with T-DM1. * Excessive alcohol intake should be avoided (occasional use is permitted). * Patients with a history of ipsilateral DCIS are eligible. * Patients undergoing breast conservation therapy (i.e. lumpectomy) must not have any contraindications to radiation therapy. * Willing and able to sign informed consent. * Willing to provide tissue for research purposes. Exclusion Criteria: * Pregnant or nursing women due to the teratogenic potential of the study drugs. * Active, unresolved infection. * Receipt of intravenous antibiotics for infection within 7 days prior to enrollment. * Patients with active liver disease, for example, due to hepatitis B virus, hepatitis C virus, autoimmune hepatic disorder, or sclerosing cholangitis. * Uncontrolled hypertension (systolic \>180 mm Hg and/or diastolic \>100 mm Hg) or clinically significant (i.e. active) cardiovascular disease: cerebrovascular accident/stroke or myocardial infarction within 6 months prior to first study medication, unstable angina, congestive heart failure (CHF) of New York Heart Association (NYHA) Grade II or higher, or serious cardiac arrhythmia requiring medication. * Significant symptoms (Grade ≥2) peripheral neuropathy. * Other concurrent serious diseases that may interfere with planned treatment, including severe pulmonary conditions/illness, uncontrolled infections, uncontrolled diabetes. * Any prior treatment for the current breast cancer, including chemotherapy, hormonal therapy, radiation or experimental therapy.