Research Article
Boekhout AH, Werkhoven ED,
Abstract
Background: Trastuzumab treatment is associated with cardiac dysfunction. We evaluated the incidence of cardiotoxicity during and long-term after trastuzumab treatment in an unselected early breast cancer population. Methods: This study included a retrospective part, the chemotherapy- and trastuzumab treatment period and a prospective part, the period of data collection long-term after trastuzumab treatment. Cardiac evaluation included left ventricular ejection fraction (LVEF) changes and an evaluation of symptomatic cardiotoxicity. Cardiac events were defined as a decrease of 10 percentage points in LVEF compared with baseline and to an absolute LVEF of below 50%. Secondary outcomes included the evaluation of cardiac markers (B-type natriuretic peptide and troponins) and single nucleotide polymorphisms (SNPs) in the HER2 gene as parameters to detect or predict trastuzumab-related cardiotoxicity. Results: Overall, 105 patients were evaluable for the primary endpoint. The 3-year cumulative incidence of cardiac events was 12% (95 CI, 4%-19%). All 8 patients with a cardiac event were pre-treated with anthracyclines and cyclophosphamide and 7 of them recovered partially or completely. Four patients experienced symptomatic cardiotoxicity, of who 2 recovered completely and the other 2 recovered partially. No statistically significant association was observed between cardiac events and cardiac markers or SNPs. Conclusion: Trastuzumab treatment in combination with anthracy cline-based chemotherapy is associated with significant and only partly reversible cardiac dysfunction. Baseline LVEF value is a prominent predictor for long-term LVEF especially, in patients who are not treated with anthracycline-based chemotherapy. These findings can be used to establish optimal monitoring strategies in trastuzumab treatment.