Cardiac troponin autoantibodies in breast cancer patients receiving adjuvant cardiotoxic chemotherapy: the PRADA study

The release of cardiac troponins (cTn) is an established sign of myocardial injury. Immunoassays that measure cardiac troponins in blood samples are used for the diagnosis of acute myocardial infarction and myocarditis, but also for monitoring cardiotoxicity in patients receiving chemotherapy. Endogenous anti-troponin autoantibodies (cTnAAb) may interfere with cTn measurements or bind to circulating cTn and form macrotroponin complexes with reduced clearance. It has been estimated that approximately 9% of the general population have cTnAAbs in circulation. However, the prevalence of cTnAAb has only been studied in few and selected cohorts and very little is known of their production. While cTn assays are used for the evaluation of chemotherapy-induced cardiotoxicity, nothing is known yet of cTnAAb in cancer patients.

The aim of this preliminary study was to investigate whether breast cancer patients produce cTnAAb to the circulation and how this production varies during the course of cardiotoxic chemotherapy.

We analysed the presence of cTnAAb with an in-house immunoassay in heparin plasma samples of 66 breast cancer patients receiving potentially cardiotoxic chemotherapy of the PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) cohort. The assay provides a semi-quantitative result that reflects the titer and affinity of the cTnAAb in the circulation. For the patients, who were found cTnAAb-positive, we analysed heparin plasma samples taken at 5 time points (including 1-year follow-up).

Of the patients analysed, two (3 %) were found cTnAAb-positive. The patients tested positive at all 5 time points. There was a significant difference in the cTnAAb signal levels (median [25th-75th percentile], 55700 [45757-66075] vs 5669 [5131-7642] counts, p<0.05) between the two patients. The titer and affinity of the cTnAAbs was in steady decline for the first three samples, but increased notably for the fourth sample for both patients. Decline in the signals was detected again in the 1-year follow-up.

In this preliminary study, the prevalence of cTnAAb in breast cancer patients receiving cardiotoxic chemotherapy was comparable to general population. In cTnAAb-positive patients similar changes in the titer and affinity of cTnAAbs during the course of treatment were detected, raising a suspicion of chemotherapy-affected autoantibody production.