BACKGROUND:

The classic biomarkers troponin and brain natriuretic peptide (BNP), as well as the currently available risk scores, are far from being considered ideal for predicting cancer therapy-related cardiac dysfunction (CTRCD). MicroRNAs (miRNAs) are promising biomarkers for better identification of high-risk patients, with little evidence in patients with HER-2 positive breast cancer.

OBJECTIVE:

To evaluate the predictive capacity of six serum circulating miRNAs for the development of CTRCD in patients with HER-2+ early breast cancer in treatment with trastuzumab (TTZ).

MATERIALS AND METHODS:

A prospective cohort study was conducted including consecutive women aged ≥18 years with HER2+ early breast cancer from breast oncology outpatient clinic between March 2019 and March 2022.

CTRCD:

reduction in left ventricular ejection fraction (LVEF) >10 percentage points to below 53%. Blood samples were collected before the start of TTZ. The miRNA quantification was determined by RT-PCR. The patients were divided into those with low and high expression of the 6 studied miRNAs (let-7f-5p, miR-1-3p, 20a-5p, 126-3p, 130-3p and 210a-3p). The best miRNAs cut-off points were determined by the Youden index. Survival analysis was performed using Kaplan-Meier curves, compared by the log-rank test. P-values < 0.05 were considered statistically significant.

RESULTS:

Forty-seven patients (mean age: 53.1±13.2y) were studied and followed for a median of 14.2 (IQR: 10.9-24.5) months (71.5 patient-years). Doxorubicin was used in the treatment of 22 (46.8%) patients. CTRCD was observed in 6 (12.8%) patients. Patients with high miR-20a-5p, 126-3p, 130-3p, and 210-3p expression levels before TTZ had lower CTRCD-free survival (all P<0.05). High levels of miR-126-3p and 130-3p had a sensitivity of 100% and specificity of 53.7 and 48.8%, respectively, to predict the development of CTRCD.

CONCLUSION:

In this pilot study of patients with early HER-2+ breast cancer, elevated miRNA expression before starting TTZ predicted lower CTRCD-free survival. Since high levels of miR-126-3p and 130-3p were observed in all patients with CTRCD, they appear to have the potential for identifying high-risk patients for the development of cardiotoxicity.