Although the detailed mechanisms of the trastuzumab-induced cardiotoxicity still remained unclear, the possible explanation was that trastuzumab intercepted neoreguline-1 (NRG-1)-mediated HER2 activation to inhibit fundamental intracellular mechanisms of cardiomyocytes (including the ability to maintain the structure and function of sarcomeres), subsequently causing the increase of accumulating cardiotoxicity in HER2-positive breast cancer patients (8, 23, 24). Here, NRG1 is linked to breast cancer.