Circulating biomarkers for diagnosis of doxorubicin-induced cardiotoxicity in breast cancer patients: A prospective observational study

Background and objectives Doxorubicin is an effective chemotherapeutic agent, whose clinical use is limited by cumulative doxorubicin-induced cardiotoxicity. Early identification of myocardial injury is essential to prevent irreversible cardiac dysfunction. This study evaluated changes in cardiac function and circulating biomarkers associated with early doxorubicin-induced cardiotoxicity. Methods Left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) were assessed before and after chemotherapy. Circulating biomarkers, including high-sensitivity C-reactive protein (hs-CRP), high-sensitivity troponin I (hs-Troponin I), Interleukin-33 (IL-33), and miR126-3p, were analysed. Associations between biomarkers and echocardiographic indicators of subclinical cardiac dysfunction were evaluated. Results Significant reductions in LVEF (65.00±2.17% to 59.50±5.47%) and GLS (−19.04±1.87% to −15.37±1.79%), increased hs-CRP, and moderate elevations in IL-33 and significant reduction of miR126-3p were observed following doxorubicin therapy. There was a significant association between LVEF with hs-Troponin I ( P =0.03) and IL-33 ( P =0.04), whereas between GLS with hs-Troponin I ( P =0.04), IL-33 ( P =0.04), and miR126-3p ( P= 0.006). Among biomarker inter-association, hs-Troponin I was highly significantly associated with IL-33 ( P <0.01), whereas no significant associations were observed between hs-CRP and other biomarkers. Interpretation and conclusions Early alterations in left ventricular function and circulating biomarkers were associated with doxorubicin chemotherapy; GLS and hs-Troponin I were associated with myocardial dysfunction, while IL-33 and miR126-3p showed additional associations with strain parameters.