Changes in circulating miR-199a, cardiac troponin I, NT-proBNP, and left ventricular ejection fraction during anthracycline therapy in breast cancer patients

Anthracyclines are widely used in the treatment of breast cancer but are associated with myocardial injury that may progress to cardiac dysfunction. Surveillance has traditionally relied on left ventricular ejection fraction (LVEF), which may not detect early subclinical injury. Circulating biomarkers, including cardiac troponin I (cTnI), NT-proBNP, and microRNAs such as miR-199a, have been proposed as potential early indicators of anthracycline-related myocardial injury. This study aimed to exploratorily evaluate early biomarker changes during anthracycline therapy and their relationship to short-term LVEF variability. In this single-center prospective observational study, women with non-metastatic breast cancer receiving anthracycline-based chemotherapy were enrolled between April 2022 and May 2024. Cardiac biomarkers (cTnI, NT-proBNP, and plasma miR-199a) and echocardiographic LVEF were assessed at baseline and after four cycles of dose-dense doxorubicin/cyclophosphamide. Within-patient changes were analyzed using Wilcoxon signed-rank tests. Associations between changes in biomarkers, LVEF, and cumulative doxorubicin dose were assessed using Spearman’s rank correlation. Exploratory subgroup analyses were performed based on the presence or absence of any absolute LVEF decrease. Forty-eight patients were enrolled, and 45 with complete paired data were included in the final analyses (mean age 41.4 ± 11.6 years). cTnI and plasma miR-199a levels increased significantly following chemotherapy (both p < 0.001), whereas NT-proBNP showed no significant change. Median LVEF remained unchanged at the cohort level and was not significantly correlated with changes in cTnI, NT-proBNP, or miR-199a. Cumulative doxorubicin dose was inversely correlated with change in LVEF (ρ = −0.424, p = 0.004). In this prospective cohort of breast cancer patients treated with anthracycline-based chemotherapy, circulating cTnI and miR-199a increased early during treatment, while cohort-level LVEF remained stable over short-term follow-up. Changes in these biomarkers were not associated with contemporaneous changes in LVEF, whereas higher cumulative anthracycline exposure was associated with a modest reduction in LVEF.