Simple SummaryTakotsubo syndrome (TTS), also known as “broken heart” syndrome, is a rare but serious heart event associated with physical or emotional stress. Patients usually complain about intense chest pain and difficulty in breathing, resembling acute myocardial infarction. Cancer patients are more likely to suffer from TTS and the condition has been linked with the use of several anticancer remedies, such as chemotherapy and targeted therapy. Immunotherapy is a new, viable option for many patients and is currently used in the management of several cancers. There are emerging reports of TTS in cancer patients treated with immunotherapy; however, its causality on TTS development remains uncertain. As TTS may be life-threatening and impact anticancer management, it is crucial to identify any possible association with immunotherapy. In this literature review, we tried to explore the extent of the condition in immunotherapy-treated patients, and to provide information regarding accurate diagnosis, management, and outcomes.AbstractBackground: There are emerging reports of Takotsubo syndrome (TTS) in cancer patients treated with immune checkpoint inhibitors (ICIs); however, the association of the two remains uncertain. Methods: A systematic literature review was performed in the PubMed database and web sources (Google Scholar) according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines. Case reports/series or studies including cancer patients treated with ICIs and presenting with TTS were considered. Results: Seventeen cases were included in the systematic review. Most patients were males (59%) with median age of 70 years (30–83). Most common tumor types were lung cancer (35%) and melanoma (29%). Most patients were on first-line immunotherapy (35%) and after the first cycle (54%) of treatment. The median time on immunotherapy at the time of TTS presentation was 77 days (1–450). The most used agents were pembrolizumab and the combination of nivolumab–ipilimumab (35%, respectively). Potential stressors were recognized in 12 cases (80%). Six patients (35%) presented with concurrent cardiac complications. Corticosteroids were used in the management of eight patients (50%). Fifteen patients (88%) recovered from TTS, two patients (12%) relapsed, and one patient died. Immunotherapy was reintroduced in five cases (50%). Conclusion: TTS may be associated with immunotherapy for cancer. Physicians should be alert for TTS diagnosis in any patient with myocardial infarction-like presentation under treatment with ICIs.