Abemaciclib-induced myocarditis in early breast cancer: a case report

BACKGROUND: Abemaciclib, a selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor, is standard adjuvant therapy for hormone receptor (HR)-positive, HER2-negative early breast cancer. While gastrointestinal and haematologic toxicities are well recognised, cardiotoxicity—particularly myocarditis—is extremely rare. To our knowledge, myocarditis has not previously been reported in early breast cancer. This case describes a case of acute abemaciclib-induced myocarditis and explores a potential genetic predisposition involving an RHBDF2 germline variant affecting growth factor signalling pathways. CASE PRESENTATION: A 39-year-old female with high-risk HR-positive, HER2-negative early breast cancer commenced adjuvant abemaciclib with letrozole following completion of chemotherapy and radiotherapy. Within 24 h, she developed acute chest pain with an elevated troponin I (8457 ng/L), new T-wave inversion on her ECG, and a reduced left ventricular ejection fraction (47%) on echocardiography. CT imaging excluded coronary or aortic pathology. Cardiac magnetic resonance imaging demonstrated mid-inferoseptal late gadolinium enhancement consistent with acute myocarditis. Abemaciclib was immediately discontinued, and bisoprolol and ramipril were initiated. Her symptoms and cardiac function improved rapidly, with normalisation of left ventricular ejection fraction (68%). Genetic testing identified a germline RHBDF2 missense variant, which is predicted to alter tumour necrosis factor alpha and epidermal growth factor signalling, potentially predisposing to cardiomyocyte injury based on published in vitro evidence. CONCLUSIONS: To our knowledge, this is among the earliest reported cases of abemaciclib-induced myocarditis in early breast cancer. Awareness of this potential toxicity is crucial, as early recognition and management is pivotal to prevent lasting cardiac dysfunction. Genetic variants influencing inflammatory or growth factor pathways may contribute to individual susceptibility, warranting further investigation. This case highlights the importance of combined cardio-oncology care in the early recognition of cardiotoxicity when introducing CDK4/6 inhibitors.