Photo Credit: Md Ariful Islam
The following is a summary of “Macrotroponin interference and association with cardiotoxicity in patients receiving cardiotoxic breast cancer therapy: a pilot study,” published in the February 2025 issue of the Cardio-Oncology by Soosaipillai et al.
Cancer therapy-related cardiac dysfunction (CTRCD) is a significant adverse effect observed in patients undergoing potentially cardiotoxic cancer treatments, necessitating accurate cardiac biomarker interpretation for effective monitoring. However, the presence of macrotroponin—an immune complex that can lead to persistently elevated troponin levels without true myocardial injury—can complicate the assessment of cardiac troponin results in this population. This pilot study aimed to investigate whether macrotroponin is detectable in women with ERBB2-positive breast cancer receiving sequential anthracycline and trastuzumab therapy and to assess its potential impact on CTRCD evaluation.
A total of 20 serum samples were analyzed from 12 patients (median age: 55 years, range: 30–69 years) who exhibited a significant increase in high-sensitivity cardiac troponin I (hs-cTnI) from baseline following anthracycline therapy (~2 months after initiation) and/or 3 months into trastuzumab therapy (~5 months after initiation), or had at least one hs-cTnI value exceeding the female-specific 99th percentile threshold (>16 ng/L). Samples were evaluated using the Abbott STAT High-Sensitive Troponin-I and Roche Elecsys Troponin T hs STAT assays. Macrotroponin was identified through protein G treatment, with its presence defined by a recovery of <40% for hs-cTnI or <85% for hs-cTnT after re-measurement. The results demonstrated that macrotroponin was not detected following anthracycline administration but was present in four patients at the 3-month mark of trastuzumab therapy, including two individuals with hs-cTnI concentrations above the 99th percentile.
Notably, none of these patients exhibited a significant reduction in left ventricular ejection fraction (LVEF) or global longitudinal strain (GLS), despite elevated hs-cTnI levels. These findings highlight the potential for macrotroponin to confound the interpretation of hs-cTn results, leading to unnecessary concerns regarding myocardial injury in patients undergoing cancer therapy. Consequently, clinicians should remain vigilant when evaluating elevated cardiac troponin levels in this setting, as the presence of macrotroponin may contribute to misleading biomarker elevations that do not necessarily indicate CTRCD. Further research with larger patient cohorts is warranted to refine troponin interpretation strategies in oncology patients and develop standardized approaches to distinguish pathological troponin elevations from benign macro troponin-related increases.
Source: cardiooncologyjournal.biomedcentral.com/articles/10.1186/s40959-025-00314-9
