There have been no reports of anti-human epidermal growth factor receptor – 2 ( HER2 ) therapies causing cytokine storms. We describe a patient with breast cancer who received trastuzumab / pertumabus treatment and who, six months after beginning double anti-HER2 therapy, experienced severe biventricular dysfunction and cardiogenic shock ( CS ). Serious systemic inflammation accompanied the CS, and cardiac MRI( cMRI ) revealed structural changes typical of myocardial inflammation. In contrast to NK cell activation, the immuno-inflammatory profile showed significantly higher levels of complement system, proinflammatory cytokines ( IL – 1 & beta, IL – 6, 18, 17A, and TNF-alpha ) activity, as well as increased activity of classical monocytic, T helper 17 cells( Th17 ), CD4 T and effector memory CD8 T subsets. The findings imply that monocytes play a significant role in initiating this FcR-dependent antibody cytotoxicity, which results in the overactivation of an adaptive T cell response in which Th17 cells may work in concert with T helper 1 cells( Th1 ) to induce the severe cellularkine release syndrome. Hypercytokinemia and complement activity returned to normal following the discontinuation of trastuzumab / pertuzim, and clinical recovery also occurred. Within two months of the initial presentation, cardiac function returned to normal, and the myocardial inflammation on the MRI was resolved.