t-dm1+pertuzumab in pre-op early-stage her2+ brca

Conditions: HER-2 Positive Breast Cancer; Breast Cancer; Stage II Breast Cancer; Stage III Breast Cancer

Summary: 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.

Eligibility criteria:
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.