Neuregulin1ß and galectin3: novel biomarkers in breast cancer

Abstract

Introduction: Neuregulins (NRGs) are proteins that activate the ErbB2 receptors in human breast tumors. NRGs have cardioprotective effects. The cerbB2 positive breast cancer patients are treated with Trastuzumab, a monoclonal antibody that can induce a clinically significant cardiomyopathy. Galectin 3 (Gal-3) expression is implicated in a variety of processes associated with heart failure, including myofibroblast proliferation, fibrogenesis, tissue repair, inflammation, and ventricular remodeling. We have measured serum NRGs and Gal-3 and correlated them to cardiac biomarkers in patients with breast cancer undergoing chemotherapy. Methods: We have evaluated circulating NRG-1beta and Gal-3 in 30 breast cancer patients without cardiovascular risk factor (median age 60 years) in treatment with Anthraciclyne and Taxanes, with or without Trastuzumab (15 cerbB2 positive and 15 cerbB2 negative) correlating these data with NT-proBNP, CK-MB and Troponine before every course of chemotherapy and in 30 healthy controls. Results: At baseline, circulating NRG-1beta and Gal-3 were significantly elevated either in cerbB2 negative or in cerbB2 positive patients with respect to healthy volunteers: in cerbB2 positive NRG mean (SD) 1,21 (1,0) ng/ml, GAL-3 mean (SD) 15,09 (3,13) ng/ml; in cerbB2 negative NRG mean (SD) 3,36 (30) ng/ml, GAL-3 mean (SD) 23,81 (9,675) ng/ml; in controls: 0 ng/ml. Plasma NRG-1beta and GAL-3 concentration remained elevated without any significant modification after each cycle of chemotherapy in both cohorts of patients: in cerbB2 positive NRG mean (SD) 2,42 (1,2) ng/ml, GAL-3 mean (SD) 16,43 (3,40) ng/ml; in cerbB2 negative NRG mean (SD) 4,5 (3,12) ng/ml, GAL-3 mean (SD) 25,13 (9,607). NT-proBNP in cerbB2 positive mean 180 pg/ml; in cerbB2 negative mean 270 pg/ml, above the upper limit of 130 pg/ml. CK-MB levels in cerbB2 positive mean 5 ng/ml; in cerbB2 negative mean 10 ng/ml, above the upper limit of 3,6 ng/ml, resulting significantly higher in cerbB2 negative then in cerbB2 positive patients. Troponine levels remained below the cutoff of 0.08 ng/ml in both groups. Conclusions: Serum NRG and GAL-3 together with cardiac biomarkers measurements could be a useful tool for the early detection of patients at high risk of developing cardiotoxicity.