Detection of Macrotroponin in Patients Receiving Treatment for Breast Cancer

One important variable to consider in patients with persistent elevations of hs-cTn with unclear etiology is an interference, such as macrotroponin, with an estimated <5% prevalence in hospital settings.1,2 Different hs-cTn assays are more apt to detect these immunoglobulin-based complexes. Although potentially persistent, identification of these complexes does not appear to be pathological.2 We and others have previously reported on the high incidence of myocardial injury (i.e., >50%) as determined by hs-cTn, in women with breast cancer within the first three months after starting trastuzumab following an anthracycline chemotherapy regimen.3 As these hs-cTn elevations did not correlate with a worsening left ventricular ejection fraction (LVEF), our objective was to explore the possibility of the presence of a macrocomplex contributing to the observed high hs-cTn concentrations. Plasma samples from the last five consecutive women who completed the study protocol (from 23 patients enrolled) were collected before chemotherapy and prior to plus one day post cycles 1-9 of trastuzumab (15 samples per patient, frozen below -700C) from our observational biomarker study (all five women has sufficient plasma volume to perform the analyses).3 The samples were tested with Abbott hs-cTnI (sex-specific upper reference limit, URL=16ng/L), Beckman hs-cTnI (12ng/L), Ortho hs-cTnI (9ng/L), Roche hs-cTnT (9ng/L) and Roche NT-proBNP (overall URL=125ng/L) with the concentrations divided by the URL to standardize interpretation. The baseline and cycle-1,-2,-9 samples were also subjected to polyethylene glycol (PEG) precipitation and tested with the Abbott hs-cTnI assay to detect the presence of macrocomplexes (macrocomplex present if PEG hs-cTnI recovery <20%).2,4 All five women (age range=36-56 years) completed the same anthracycline regimen (duration range=70-88 days) followed by 9 cycles of trastuzumab with blood collected. Before treatment (pre-chemo), only the Abbott hs-cTnI assay yielded concentrations above the limit of detection (range=5-13ng/L) in all samples (Supplemental Table S1), with a macrocomplex also detected with the Abbott hs-cTnI assay for these five patients. The increase in hs-cTn was similar across all assays, with highest levels (average=5xURL) around cycle-2 of trastuzumab (average=96 days on treatment), which was dissimilar to the NT-proBNP profile (Figure 1). A larger study is necessary to determine macrotroponin prevalence in breast cancer patients using the systematic approach recently published by the International Federation of Clinical Chemistry Committee on Clinical Applications of Cardiac Biomarkers.4 However, these exploratory data suggests that these macrocomplexes might explain some of the early hs-cTn elevations in this population with normal LVEF. Funding: Juravinski Cancer Center Foundation Grant (Dr Dhesy-Thind) and CIHR (Kavsak) Ethics approval: Study was approved by the Hamilton Integrated Research Ethics Board Conflict of interest/Disclosures: Dr. Kavsak has received grants/reagents/consultant/advisor/ honoraria from Abbott Laboratories, Abbott Point of Care, Beckman Coulter, Ortho Clinical Diagnostics, Quidel, Randox Laboratories, Roche Diagnostics, Siemens Healthcare Diagnostics, and Thermo Fisher Scientific. McMaster University has filed patents with Dr. Kavsak listed as an inventor in the acute cardiovascular biomarker field. No other disclosures were reported. 1Saunders A, Tsui AKY, Alhulaimi N. Persistent Troponin Elevation in the Setting of an Elevated Rheumatoid Factor: When It Pays to Double Check. CJC Open. 2021 Mar 3;3(7):981-983.Google Scholar, 2Ghossein J, Ghossein J, Booth RA, Kavsak P, Chamoun C. Presence of Macrotroponin for Over 2 Years in a Young Woman. CJC Open. 2022 Aug 6;4(11):1012-1014.Google Scholar, 3Dhesy-Thind S, Ellis PM, Mukherjee SD, Mackett K, Bordeleau L, Kavsak PA. Longitudinal High-Sensitivity Cardiac Troponin I Measurements in Patients With Breast Cancer Receiving Trastuzumab. Can J Cardiol. 2019 Apr;35(4):545.e1-545.e2.Google Scholar, 4Hammarsten O. Warner J.V. Lam L. Kavsak P. Lindahl B. Aakre K.M. Collinson P. Jaffe A.S. Saenger A.K. Body R. Mills N.L. Omland T. Ordonez-Llanos J. Apple F.S. Antibody-mediated interferences affecting cardiac troponin assays: recommendations from the IFCC Committee on Clinical Applications of Cardiac Biomarkers.Clin Chem Lab Med. 2023 Mar 24; https://doi.org/10.1515/cclm-2023-0028Crossref Scopus (0) Google Scholar. Download .docx (.01 MB) Help with docx files

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