Using Biomarkers to Detect the Temporal Trend of Subclinical Cardiotoxicity in Patients with Breast Cancer Treated with Anthracyclines and Her2+ Antagonists

ABSTRACT Background: Standard of care treatment for human epidermal growth factor receptor 2 (HER2) positive (HER2+) breast cancer often involves HER2 antagonism and anthracyclines. Anthracyclines and HER2 antagonists are associated with cardiotoxicity and cardiac screening is suggested. The optimal strategy for cardiac monitoring is not definitively established and the potential role of biomarkers to detect subclinical cardiotoxicity is an active area of interest within the field of cardio-oncology. Methods: This single center retrospective cohort analysis, examined the role of troponin I (Tp I) to detect subclinical cardiotoxicity and predict subsequent cardiovascular dysfunction in patients undergoing treatment for HER2+ breast cancer treated with combination trastuzumab and pertuzumab therapy. Subjects were identified by review of cardio-oncology and medical oncology clinical registries. Demographic and clinical data were obtained through chart review. Tp I absolute values and temporal trends, and subsequent decline in left ventricular ejection fraction or development of symptomatic heart failure were evaluated and compared for different chemotherapeutic regimens. Results: The incidence of Tp I elevation was significantly higher in patients treated with both anthracycline and HER2 antagonism when compared to patients treated with anthracycline or HER2 antagonism alone. In patients treated with both anthracycline and HER2 antagonism (either trastuzumab alone or in combination with pertuzumab), Tp I levels became positive (greater than 0.03 ng/mL) after the completion anthracycline therapy and 3.8 + 1.93 infusions of anti-HER2 therapy. The average peak Tp I was 0.104 + 0.05. Resolution of Tp I elevation occurred by infusion 14 + 1.94. Conclusions: Patients treated with a combination of anthracycline and HER2 antagonism, demonstrated elevated Tp I values with peak Tp I occurring after completion of anthracyclines and approximately 7 infusions of HER2 antagonist therapy.