Abstract
In breast cancer management, predicting axillary lymph node (ALN) metastasis using whole-slide images (WSIs) of primary tumor biopsies is a challenging and underexplored task for pathologists. We developed METACANS, an multimodal artificial intelligence (AI) model that integrates WSIs with clinicopathological features to predict ALN metastasis. METACANS was trained on 1991 cases and externally validated across five cohorts with a total of 2166 cases. Across all validation cohorts, METACANS achieved an area under the curve (AUC) of 0.733 (95% CI, 0.711-0.755), with an overall negative predictive value of 0.846, sensitivity of 0.820, specificity of 0.504, and balanced accuracy of 0.662. Without additional annotations, METACANS identified pathological imaging patterns linked to metastatic status, such as micropapillary growth, infiltrative patterns, and necrosis. While its predictive performance may not yet support immediate clinical application, METACANS addresses the task of predicting ALN metastasis using WSIs and clinicopathological features, and demonstrates the feasibility of multimodal AI approaches for preoperative axillary staging in breast cancer.