Cardiac Safety Study in Patients With HER2 + Breast Cancer

Title: A pilot study evaluating the cardiac safety of HER2 targeted therapy (non-lapatinib) in patients with HER2 positive breast cancer and reduced left ventricular function Phase: Pilot study Study Duration: 4 years with up to 5 additional years of follow up Study Center(s): 3 centers will be participating: MedStar Washington Hospital Center (MWHC), MedStar Georgetown University Hospital (MGUH) and Memorial Sloan Kettering Cancer Center (MSKCC) Primary Objective: To evaluate the cardiac safety of HER2 targeted therapy (non-lapatinib) in patients with HER2 positive breast cancer and reduced left ventricular ejection fraction (LVEF) when given concomitantly with cardiac treatment. Secondary Objectives: * To evaluate time to development of cardiac event or asymptomatic worsening of cardiac function * Absolute changes in LVEF * Delays in HER2 therapy attributed to cardiac causes * Correlations between echocardiographic myocardial strain * cTnI and hs-cTnT at baseline and over time with cardiac events and asymptomatic worsening of cardiac function Sample size: 30 patients Diagnosis and Main Inclusion Criteria: * HER2 positive breast cancer, stage I-IV. * Mildly decreased cardiac function (LVEF between 40 and 49%) prior to or while receiving non-lapatinib HER2 targeted therapy Cardiac Intervention: \- Beta-blockers and ACE-inhibitors titrated to the maximum tolerated doses Oncology study Products, Doses, Routes, Regimens: * Trastuzumab: loading dose of 8 mg/kg IV, followed by a maintenance dose of 6 mg/kg every 3 weeks, or a loading dose of 4 mg/kg followed by a maintenance dose of 2 mg/kg every week. * Pertuzumab: loading dose of 840 mg IV, followed by 420 mg IV every 3 weeks, administered concomitantly with trastuzumab. * Ado-trastuzumab emtansine: 3.6mg/kg IV every three weeks. Note: both trastuzumab and pertuzumab may be administered alone or in combination with other systemic or radiation therapy. Duration of drug administration: Maximum of 12 months.