A fibrosis biomarker early predicts cardiotoxicity due to anthracycline-based breast cancer chemotherapy
Simple Summary Left ventricular dysfunction (LVD) induced by anthracycline-based cancer chemotherapy (ACC) is becoming an urgent healthcare concern. Myocardial fibrosis (MF) may contribute to LVD after ACC. We show that elevated circulating levels of procollagen type I C-terminal propeptide (PICP, biomarker of MF) are associated with early subclinical LVD and predict later development of cardiotoxicity in patients treated with ACC. In addition, an association between PICP and LVD in patients with ACC-induced heart failure is observed. These results provide novel insights into MF as a mechanism underlying LVD after ACC, with PICP emerging as a promising tool to monitor cardiotoxicity in patients treated with ACC. 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.