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We report a patient with breast cancer treated with trastuzumab\/pertuzumab who developed severe biventricular dysfunction and cardiogenic shock (CS) 6 months after starting double anti-HER2 therapy. The CS was accompanied by severe systemic inflammation, and cardiac MRI (cMRI) showed structural changes typical of myocardial inflammation. The immuno-inflammatory profile showed significantly increased levels of activation of the complement system, proinflammatory cytokines (IL-1\u03b2, IL-6, IL-18, IL-17A, TNF-alpha) with increased activity of classical monocytic, T helper 17 cells (Th17), CD4 T and effector memory CD8 T subsets, whereas NK cell activation was not observed. The data suggest an important role for monocytes as initiators of this Fc\u03b3R-dependent antibody-dependent cytotoxicity, leading to the overactivation of an adaptive T cell response, in which Th17 cells may act in synergy with T helper 1 cells (Th1) to drive the severe cytokine release syndrome. After discontinuation of trastuzumab\/pertuzumab, hypercytokinemia and complement activity normalized along with clinical recovery. Cardiac function returned to baseline within 2\u2009months of initial presentation, together with a resolution of the myocardial inflammation on MRI.<\/jats:p>","DOI":"10.1136\/jitc-2023-006942","type":"journal-article","created":{"date-parts":[[2023,6,28]],"date-time":"2023-06-28T14:15:43Z","timestamp":1687961743000},"page":"e006942","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Cytokine storm complicated by cardiogenic shock induced by anti-HER2 therapies"],"prefix":"10.1136","volume":"11","author":[{"given":"Rita","family":"Godinho","sequence":"first","affiliation":[{"name":"Department of Heart-Vessels, Lausanne University Hospital CHUV, Lausanne, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Noto","sequence":"additional","affiliation":[{"name":"Department of Medicine, Immunology and allergy division, Lausanne University Hospital CHUV, Lausanne, 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