Circulating biomarkers for diagnosis of doxorubicin-induced cardiotoxicity in breast cancer patients: A prospective observational study
Lakshmi V. Divya, Ashok Govindaraj, Anita Ramesh Chandra, Gnanaguru D., Abishkauf Jenish Beautlin, Jayapriya S.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.