Evaluating Changes in Heart Function in HER2+ Stage I-III Breast Cancer Patients Who Have Been Treated with Anthracycline and/or Trastuzumab and Pertuzumab-based Cancer Therapy

PRIMARY OBJECTIVES:

I. To create a registry of both clinical and echocardiographic variables that will be used to develop a risk model to predict LV dysfunction in early stage breast cancer patients undergoing chemotherapy with anthracycline and/or trastuzumab and pertuzumab-based regimens.

II. To propose a new management algorithm for initiation of prophylactic beta blocker therapy for early stage breast cancer patients with preclinical cardiac toxicities demonstrated by strain parameters.

III. To determine if initiation of prophylactic beta-blocker therapy in patients with early cardiac toxicity can prevent a worsening of strain.

IV. To explore serial measurements of a suite of biomarkers (high sensitivity troponin [hs TnI], brain natriuretic protein [BNP], galectin 3, growth differentiation factor 15 [GDF-15], (phosphatidylinositol glycan anchor biosynthesis [PIGF]) during ongoing anticancer treatment that are presumed but not yet proven to be predictive of cardiac dysfunction in women with breast cancer.

V. To identify deoxyribonucleic acid (DNA) biomarkers of predilection to cardiotoxicity.

VI. To generate human induced pluripotent stem cells (hiPSC) to validate markers predictive of cardiotoxicity.

OUTLINE:

Prior to the initiation of chemotherapy, patients undergo echocardiogram per standard of care at baseline.

Based on echocardiogram findings, patients with normal ejection fraction (EF) and normal strain are assigned to Arm A , and patients who present with a decrease in EF > 10% to a value < 53% are assigned to Arm D. Patients with normal EF who develop abnormal strain measurements are randomized to Arm B (prophylactic beta blocker medication) or Arm C (no prophylactic treatment).

ARM A: Patients receive standard of care chemotherapy and undergo echocardiogram every 3 months for 12 months.

ARM B: Patients receive carvedilol orally (PO) twice daily (BID) for up to 1 year in the absence of disease progression or unacceptable toxicity. Patients also undergo echocardiogram every 3 months for 12 months until completion of trastuzumab/pertuzumab chemotherapy.

ARM C: Patients undergo echocardiogram every 3 months for 12 months until completion of trastuzumab/pertuzumab chemotherapy.

ARM D: Patients withhold standard of care chemotherapy. Patients then receive standard of care heart failure therapy and undergo echocardiogram every 1 month to determine if anti-cancer treatment can be resumed.

BIOMARKER SUB-STUDY:

At the same time as the trastuzumab infusions, patients undergo and collection of blood samples for biomarkers and genetic testing at baseline, every 6 weeks for 12 months, and at 1 year post-chemotherapy. Patients undergo standard echocardiogram. Patients in Arm B and C also undergo additional 4D strain and 4D volume assessment at completion of the study.