KCNJ12 differential up-regulation in patients treated with trastuzumab and an anthracycline.

Up to 27% percent of breast cancer patients receiving adjuvant trastuzumab in the presence of an anthracycline experience cardiotoxicity (1) but the mechanism of action for this is not understood (2-4). We compared whole gene expression between the primary tumors of patients receiving adriamycin and cyclophosphamide (AC chemotherapy) and those receiving ACT (AC chemotherapy with adjuvant trastuzumab) using published microarray data (5) to discover possible gene products associated with these events. We report here a gene mutated in patients with familial dilated cardiomyopathy (6), KCNJ12 among those most differentially up-regulated selectively in patients receiving ACT. Blind analysis of a separate microarray dataset (7) revealed that KCNJ12 is also selectively up-regulated in patients treated with a separate anthracycline, epirubicin, in addition to trastuzumab, suggesting that cardiotoxicity in patients treated with trastuzumab and an anthracycline is at least in part associated with KCNJ12 up-regulation.