Clinical flaws in the breast cancer ADAM10 and atrial fibrillation study

This commentary refers to ‘Breast tumour-secreted ADAM10 mediates atrial fibrogenesis and fibrillation’, by G. Xue et al., https://doi.org/10.1093/eurheartj/ehag147 We read with interest the study by Xue et al.1 reporting that breast cancer (Bc)-derived soluble ADAM10 promotes atrial fibrosis and fibrillation. While the findings are intriguing, two critical flaws undermine the causal inferences. First, the clinical comparison of atrial fibrillation (AF) prevalence between pre-treatment Bc patients and controls suffers from detection bias. Bc patients underwent electrocardiography (ECG) and Holter monitoring as part of pre-therapy evaluation, whereas controls received only a single ECG during a routine health check-up (Methods). This differential surveillance intensity inevitably inflates AF detection in the Bc group, especially for paroxysmal AF. The authors did not report Holter utilization rates nor adjust for monitoring duration. With an AF prevalence of only .90% in controls—far below the expected 2%–4% for age-matched females—the observed seven-fold higher risk is likely an artefact of ascertainment bias rather than a true tumour effect.