Cardiac troponin autoantibodies and Cancer therapy-related cardiac dysfunction in breast Cancer patients receiving anthracycline treatment: secondary analysis of the PRADA study

BACKGROUND: Cardiac troponins (cTn) are biomarkers for cardiac injury and used for detection and monitoring of cancer therapy-related cardiac dysfunction (CTRCD). However, cTn-specific autoantibodies (cTnAAb) can interfere with cTn measurements. The purpose of this study was to investigate the prevalence of cTnAAbs and whether cTnAAbs associate with the development of CTRCD in breast cancer patients receiving anthracyclines such as epirubicin. METHODS: This study included 119 patients from the PRADA trial, where study drugs metoprolol and candesartan were given concomitantly with 5-fluorouracil, epirubicin and cyclophosphamide therapy with or without trastuzumab and/or radiation. Blood samples obtained at baseline, after 1st cycle and at completion of epirubicin therapy, after possible additional treatment and at 2-year follow-up were analysed for cTnAAbs using an investigational immunoassay. RESULTS: We detected cTnAAbs in 6 patients (5%), out of whom 3 (50%) developed mild CTRCD, whereas 68 out of 113 (60%) cTnAAb-negative patients developed mild CTRCD (p = 1.0). High-sensitivity cTnI (Abbott) concentrations were higher in cTnAAb-positive than negative patients at baseline (median [95% CI] 2.1 [1.5, 6.1] vs. 0.8 [0.8, 1.2] ng/L, p < 0.001) and after the first cycle of anthracyclines (2.3 [1.1, 7.1] vs. 1.2 [0.8, 1.3] ng/L, p < 0.05) but not after completion of anthracycline therapy. CONCLUSIONS: The prevalence of cTnAAbs was low in this breast cancer cohort. The presence of cTnAAbs in circulation was associated with slightly higher initial concentrations of cTnI. No associations between the production of cTnAAbs and the development of CTRCD were observed in this study.