Arrhythmias & electrophysiologyMechanistic study
Breast tumour-secreted ADAM10 mediates atrial fibrogenesis and fibrillation
- Mechanistic study
- retrospective clinical analysis
- propensity-score matched
- orthotopic breast cancer (BC) mouse model
Authors' conclusion
BC patients before treatment present a significantly higher prevalence of AF and atrial remodelling, which correlate with elevated levels of tumour-originated sADAM10 and ACF-secreted sEphrin B2. Tumour-originated sADAM10 directly promotes AF pathogenesis by inducing atrial fibrosis, independent of cancer treatment.
Study context
- Population
- Female breast cancer patients before therapy and healthy female participants; orthotopic BC mouse model1:1 matched cohort
- Participants
- 1,217 vs 1,217
- Comparison
- Breast cancer before therapy vs non-cancer female controls
- BCn = 1,217
- Controlsn = 1,217reference
- Outcome
- Prevalence of AF
- Follow-up
- Before therapy
Main finding
As reported in the abstract
Further findings
Abnormal P-wave terminal force in ECG lead V1
P < 0.001
Plasma sEphrin B2 vs sADAM10 levels
- Correlation of sEphrin B2 with sADAM10 levels (R2 = 0.67)
- P < 0.0001
Mouse experiments
- BC mice developed atrial fibrosis and increased atrial fibrillation (AF) susceptibility
- Cardiac fibroblast-specific knockdown of Ephrin B2 suppressed AF development in BC mice
- Inhibition of sADAM10 (GI254023X or shRNA) attenuated atrial fibrosis and AF susceptibility in BC mice
Original publication
Breast tumour-secreted ADAM10 mediates atrial fibrogenesis and fibrillation. Eur Heart J. Published 5 March 2026. doi:10.1093/eurheartj/ehag147
Summarised from the published abstract; every number is checked against it