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(®) 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.