A Fibrosis Biomarker Early Predicts Cardiotoxicity Due to Anthracycline-Based Breast Cancer Chemotherapy

Abstract

Anthracycline-based cancer chemotherapy (ACC) causes myocardial fibrosis, a lesion contributing to left ventricular dysfunction (LVD). We investigated whether the procollagen-derived type-I C-terminal-propeptide (PICP): 1) associates with subclinical LVD (sLVD) at 3-months after ACC (3m-post-ACC); 2) predicts cardiotoxicity 1-year after ACC (12m-post-ACC) in breast cancer patients (BC-patients); and 3) associates with LVD in ACC-induced heart failure patients (ACC-HF-patients). Echocardiography, serum PICP and biomarkers of cardiomyocyte damage were assessed in two independent cohorts of BC-patients: CUN (n = 87) at baseline, post-ACC, and 3m and 12m (n = 65)-post-ACC; and HULAFE (n = 70) at baseline, 3m and 12m-post-ACC. Thirty-seven ACC-HF-patients were also studied. Global longitudinal strain (GLS)-based sLVD (3m-post-ACC) and LV ejection fraction (LVEF)-based cardiotoxicity (12m-post-ACC) were defined according to guidelines. BC-patients: all biomarkers increased at 3m-post-ACC versus baseline. PICP was particularly increased in patients with sLVD (interaction-p < 0.001) and was associated with GLS (p < 0.001). PICP increase at 3m-post-ACC predicted cardiotoxicity at 12m-post-ACC (odds-ratio ≥ 2.95 per doubling PICP, p ≤ 0.025) in both BC-cohorts, adding prognostic value to the early assessment of GLS and LVEF. ACC-HF-patients: PICP was inversely associated with LVEF (p = 0.004). In ACC-treated BC-patients, an early increase in PICP is associated with early sLVD and predicts cardiotoxicity 1 year after ACC. PICP is also associated with LVD in ACC-HF-patients.

New Insights in the Era of Clinical Biomarkers as Potential Predictors of Systemic Therapy-Induced Cardiotoxicity in Women with Breast Cancer: A Systematic Review

“…In addition to above-mentioned biomarkers, other potentially promising biomarkers are currently under investigation for their utility in the detection and/or prediction of CTRCD including: coronary artery calcification [ 298 ], endothelin-1 [ 299 ], neuregulin-1 [ 285 , 300 ], plasma bioactive adrenomedullin (ADM) [ 301 ], fragmented QRS (fQRS) [ 302 ], D-dimer [ 303 ], soluble fms-like tyrosine kinase receptor (sFlt)-1 [ 105 ], soluble ST2 (sST2) [ 145 , 149 , 171 , 279 , 304 ], CK-MB [ 134 , 286 ], topoisomerase II α gene ( TOP2A ) [ 305 ], cardiac myosin light chain 1 (cMLC-1) [ 306 ], vascular endothelial growth factor (VEGF) [ 93 ], placental growth factor (PIGF) [ 93 , 98 ], procollagen-derived type-I C-terminal-propeptide (PICP) [ 307 ], epicardial adipose tissue (EAT) volume [ 308 , 309 ], circulating bilirubin [ 310 ], hemopexin [ 311 ], glycated hemoglobin (HbA(1)c) [ 103 ], advanced oxidation protein products (AOPP) [ 102 ], human resistin [ 312 ] and vascular adhesion molecule 1 (VCAM-1) [ 117 ].…”