High-sensitivity cardiac troponin I detection for 2 types of drug-induced cardiotoxicity in patients with breast cancer

Abstract

Background Breast cancer treatment with trastuzumab, a monoclonal antibody that targets human epidermal growth factor receptor type 2 (HER2), has largely been successful in improving the prognosis of HER2-positive disease. However, a critical issue associated with trastuzumab treatment is its cardiotoxic adverse effects, including cardiac insufficiency. Methods We measured levels of cardiac troponin I, a marker of myocardial damage, with a highly sensitive method (hs-cTnI) using a fully automated chemiluminescent immunoassay system (ADVIA Centaur Ò XP) in breast cancer patients and examined the relationship between administration of trastuzumab and epirubicin and concentrations of hs-cTnI. Results The coefficient of variation for within-run repeatability was 1.34-5.93 %, using plasma pools and controls of 3 concentrations, and that for between-run reproducibility was 3.99-8.79 %, indicating high precision of the assay. In a dilutional linearity test with highly concentrated specimens, hs-cTnI values could be measured up to 50 ng/mL with linearity. No influence from coexisting substances was observed. The concentration of hs-cTnI was at or above the reference range (0.04 ng/mL) in 9 of 214 total breast cancer cases (4.2 %). The hs-cTnI concentration was at or above the reference range in 4 of 49 cases (8.2 %) that were administered trastuzumab, and in 5 of 165 cases (3.0 %) that were not. Trastuzumab did not cause elevation of hs-cTnI when not administered in combination with epirubicin. Conclusions These results suggest that epirubicin and trastuzumab cause cardiotoxicity through different mechanisms. Epirubicin can cause myocardial necrosis, while trastuzumab can cause cardiomyopathy without myocardial necrosis.

High-sensitive troponin T assay can predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients

“…In several cardiac biomarkers, only high-sensitive troponin assays are shown to detect not only immediately after the onset of acute myocardial infarction, but also poor cardiac prognosis of patients with cardiac failure or hypertension [14][15][16][17][18][19]. In regard to CTIC, several studies showed hs-TnI levels elevated after trastuzumab following anthracycline administration [11,12,23]. Conventional troponin T assays could not predict CTIC [13].…”

Serum biomarkers evaluation to predict chemotherapy-induced cardiotoxicity in breast cancer patients

“…Troponin is a polypeptide composed by three elements: troponin C (calcium binding), troponin I (actin-myosin binding), and troponin T (tropo-myosin binding); this protein complex has the contractile function in the cardiac striated muscle fibers, associated with actin and myosin. Tn I is present in the blood 4-8 h after clinical AMI, reaching a peak after 12-16 h and remaining detectable for 5-9 days [20]: this marker has a higher specificity, as compared to the rise of CK-MB [21]. The plasmatic increase of Tn I is therefore correspondent to a myocardial damage from acute coronary syndromes, AMI (Q and non-Q) and unstable angina, and it is associated with poor prognosis [22].…”

Fully Automated Ultrasensitive Digital Immunoassay for Cardiac Troponin I Based on Single Molecule Array Technology

“…Monitoring of cardiac troponin as measured by high-sensitivity assays is gaining acceptance for the prevention of cardiotoxicity associated with certain pharma-cotherapeutic regimens, particularly those used for cancer chemotherapy (15,16 ). Similarly, detection of even small cardiac troponin increases is an early sign of rejection of a transplanted heart and, consequently, serial cardiac troponin monitoring may guide timely modifications of immune suppression in heart transplant recipients (17 ).…”