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

Cancers

José María López Picazo¹  Marta Santisteban¹  José Manuel Aramendía¹  Antoni Bayés-Genís²  Pilar Sepúlveda²  Josep Lupón²  Ana Santaballa³  Juan José Gavira⁴  Agnes Díaz⁴  Ana de la Fuente⁴  Ignacio García-Bolao⁴  Gregorio Rábago⁴  Javier Díez⁴  Begoña López⁵  Arantxa González⁵  Manuel M. Mazo⁵  Susana Ravassa⁵  Amparo Hernándiz⁶  Germán Cediel⁷ 

[1] Breast Cancer Unit, Medical Oncology Department, Clínica Universidad de Navarra, 31008 Pamplona, Spain;CIBERCV, Carlos III Institute of Health, 28029 Madrid, Spain;Clinical and Translational Research in Cancer, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain;Department of Cardiology and Cardiac Surgery, Clínica Universidad de Navarra, 31008 Pamplona, Spain;IdiSNA, Navarra Institute for Health Research, 31008 Pamplona, Spain;Regenerative Medicine and Heart, Instituto de Investigación Sanitaria La Fe, 46026 Valencia, Spain;Servei de Cardiologia i Unitat d’Insuficiència Cardíaca, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Spain;

关键词: anthracycline-based chemotherapy;    myocardial fibrosis;    biomarkers;    global longitudinal strain;    cardiotoxicity;   

DOI  :  10.3390/cancers14122941

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown