Predicting Symptomatic Cardiotoxicity in HER2-Positive Breast Cancer Patients Treated with Trastuzumab: Insights from a Brazilian Real-World Cohort

Abstract Background Cardiotoxicity is a known adverse effect of Trastuzumab treatment. Early detection through regular cardiac imaging is crucial to prevent its progression and ensure reversibility. However, recent studies question the current cardiac monitoring approach during Trastuzumab use. Symptomatic cardiotoxicity is infrequent, and interrupting treatment based solely on imaging-assessed LVEF decline might compromise effectiveness and reduce survival. Therefore, identifying risk factors for symptomatic cardiotoxicity could enable risk stratification and guide cardioprotective measures, potentially preventing unnecessary treatment interruptions and improving outcomes. Methods We retrospectively analyzed real-world data from 131 women with HER2 + breast cancer to evaluate the occurrence of symptomatic cardiotoxicity, defined by NYHA functional classes 2, 3, or 4, during Trastuzumab treatment. Cardiac monitoring involved Equilibrium Radionuclide Angiocardiography (ERNA) to assess left ventricular systolic dysfunction, specifically a > 10 percentage point decrease in LVEF from baseline to a value below the normal limit (< 50%). Clinical data and imaging parameters were evaluated to detect risk factors associated with symptomatic cardiotoxicity onset. Results Symptomatic cardiotoxicity occurred in 13 (9.9%) of evaluated patients, while systolic ventricular dysfunction, based on adopted clinical monitoring criteria, was observed in 22 (16.7%). There was no significant difference in the occurrence of systolic ventricular dysfunction between asymptomatic patients and those with symptomatic cardiotoxicity (p = 0.231). In multivariate logistic regression analysis, baseline diastolic dysfunction, a cumulative anthracycline dose greater than 240 mg/m², and an early LVEF drop were identified as risk factors associated with the occurrence of symptomatic cardiotoxicity. Utilizing these variables, two predictive models for symptomatic cardiotoxicity were proposed. The models yielded an AUC of 0.782 (p = 0.001) for an LVEF drop cutoff of 15%, and an AUC of 0.763 (p = 0.006) for an LVEF drop cutoff of 7%. Conclusion Symptomatic cardiotoxicity occurred in 9.9% of evaluated patients. Baseline diastolic dysfunction, a cumulative anthracycline dose greater than 240 mg/m², and an early LVEF drop were identified as risk factors for developing symptomatic cardiotoxicity during Trastuzumab use.