Prediction of axillary lymph node metastasis using a transformer model and multi-omics validation in breast cancer.

Our study developed a multiomics-driven transformer model that combines mammography, MRI, transcriptomic and proteomic data to noninvasively predict axillary lymph node (ALN) metastasis in breast cancer. A total of 2105 patients from 10 institutions were included for model training and validation. The model achieved an AUC of 0.939 in the training cohort (n = 658) and 0.830-0.867 across three independent validation cohorts (n = 282, 971 and 194, respectively), outperforming conventional ultrasound examination. Grad-CAM visualizations highlighted the tumor edges and surrounding tissue, consistent with clinical and pathological findings. In a cohort of 194 patients, multiomics analyses linked the model output to gene and protein signatures involved in immune modulation, cytoskeletal remodeling, and epithelial-to-mesenchymal transition. Critically, the major enriched pathways identified through model-stratified analysis were independently replicated in a parallel non-model-driven analysis using ALN status, demonstrating that these signatures reflect tumor biology. Network analysis revealed gene clusters related to DNA replication and immune pathways, providing biological insights into the model's decisions. These findings suggest that the stacking model holds promise as a noninvasive decision-support tool that may complement, rather than replace, current clinical staging practices. However, integration into clinical workflows requires prospective validation.