MicroRNA Expression Pre-Trastuzumab Treatment in HER-2+ Early Breast Cancer Patients as a Predictor of Cancer Therapy-Related Cardiac Dysfunction: A Pilot Cohort Study.

Introduction: At present, existing risk scores together with traditional biomarkers such as troponin and brain natriuretic peptide are still unable to accurately predict cancer therapy-related cardiac dysfunction (CTRCD). MicroRNAs (miRNAs) have emerged as promising biomarkers for improved identification of high-risk patients; however, limited studies have been performed in patients with HER2-positive breast cancer. This study aimed to investigate the predictive potential of six serum-derived circulating miRNAs for CTRCD occurrence in patients with early-stage HER2-positive breast cancer receiving trastuzumab (TTZ).

Methods: A prospective cohort study was conducted involving consecutive female patients aged 18 years or older with HER2-positive early breast cancer, who attended the breast oncology outpatient clinic of the institution between March 2019 and March 2022. Blood samples were obtained prior to the initiation of TTZ therapy. CTRCD was defined as a reduction in left ventricular ejection fraction >10 percentage points, resulting in a value <53%. Quantification of miRNAs - including let-7f-5p, miR-1-3p, miR-20a-5p, miR-126-3p, miR-130-3p, and miR-210a-3p - was performed using quantitative real-time polymerase chain reaction. The optimal miRNA cutoff points were determined using the Youden index. CTRCD-free survival was analyzed using Kaplan-Meier curves, with group comparisons conducted via the log-rank test.

Results: A total of 47 patients (mean age 53.1 ± 13.2 years) were included and followed for a median of 14.2 months (IQR 10.9-24.5), corresponding to 71.5 patient-years of follow-up. Doxorubicin was administered as part of the treatment regimen in 22 patients (46.8%). Six patients (12.8%) developed CTRCD. Patients exhibiting high baseline expression levels of miR-20a-5p, miR-126-3p, miR-130-3p, and miR-210-3p prior to TTZ treatment demonstrated significantly reduced CTRCD-free survival (all p < 0.05). Elevated levels of miR-126-3p and miR-130-3p showed 100% sensitivity and specificities of 53.7% and 48.8%, respectively, for predicting the development of CTRCD.

Conclusion: This pilot study suggests that elevated expression of some miRNA prior to TTZ treatment may be associated with lower CTRCD-free survival, but these findings require confirmation in larger, prospective studies. While high levels of miR-126-3p and miR-130a-3p were observed in all patients who developed CTRCD, their potential role as biomarkers of cardiotoxicity risk should be further explored in future research with broader patient cohorts.