Early diagnostic value of novel biomarkers for breast cancer therapy‐related cardiac dysfunction

Aims This study aims to (1) evaluate the diagnostic utility of myeloperoxidase (MPO), growth differentiation factor‐15 (GDF‐15), C‐reactive protein (CRP), placental growth factor (PLGF) and galectin‐3 (Gal‐3) for cancer therapy‐related cardiac dysfunction (CTRCD) in breast cancer patients through meta‐analysis and (2) investigate causal roles using Mendelian randomization (MR). Methods We conducted a dual‐phase analysis. First, a PRISMA‐compliant (ID: CRD42023453369) meta‐analysis of 12 studies (11 prospective cohorts, 1 RCT; 917 patients; age 50.4 ± 16.0 years; median follow‐up 12 months) from five databases (PubMed/Web of Science/Embase/Cochrane/ ClinicalTrials.gov ) quantified post‐treatment biomarker changes using weighted/standardized mean differences (WMD/SMD) and CTRCD risk via hazard ratios (HRs). Second, two‐sample MR analysis leveraged MPO‐associated single nucleotide polymorphisms (SNPs) to assess causality with heart failure (HF) and cardiomyopathy, employing IVW, MR‐Egger, weighted median and simple mode methods with heterogeneity testing. Results The meta‐analysis demonstrated significant post‐treatment elevations in: MPO [US patients: SMD = 0.78, 95% confidence interval (CI) 0.45–1.12; I 2 = 72%; P < 0.00001], GDF‐15 (SMD = 0.64, 95% CI 0.24–1.05; I 2 = 77%; P = 0.002), PLGF (SMD = 0.87, 95% CI 0.10–1.63; I 2 = 95%; P = 0.03), and CRP (WMD = 0.83, 95% CI 0.46–1.20; I 2 = 18%; P < 0.0001). Subgroup analyses eliminated heterogeneity for GDF‐15 ( I 2 = 0%) and PLGF ( I 2 = 0%), while partially reducing heterogeneity for MPO ( I 2 = 72%). Elevated MPO levels predicted increased CTRCD risk in patients receiving cancer treatment (HR = 1.30, 1.10–1.54; I 2 = 0%; P = 0.002). MR analysis suggested causal relationships between MPO and both HF [odds ratio (OR) = 1.06, 95% CI 1.02–1.09; P = 0.001] and cardiomyopathy (OR = 1.09, 95% CI 1.02–1.17; P = 0.02), with significant heterogeneity detected in heart failure SNPs (Cochran's Q = 61.63, P = 0.04). Conclusions Our study suggested that MPO was associated with both diagnostic biomarker profiles and mechanistic pathways in CTRCD pathogenesis. These preliminary findings highlighted MPO as a possible target for further investigation of early CTRCD detection in breast cancer patients.