Abstract
OBJECTIVE: This research aims to develop and evaluate a clinically deployable multimodal deep learning framework for breast cancer diagnosis that maintains robustness, even when clinical data are asynchronous, unpaired, or incomplete, effectively addressing real-world challenges related to data heterogeneity and fragmented clinical workflows. METHODS: In this retrospective study, a multimodal deep learning architecture was developed that integrates histopathological images with structured clinical risk factors. Custom models were developed and independently trained for each modality, and late fusion was achieved via a dynamically reweighted Sinkhorn-based fusion layer. Model performance was evaluated using precision-recall Area Under Curve (PR-AUC), recall, F1 score, and Brier score under complete and partial modality availability scenarios. Robustness and clinical utility were further assessed through statistical significance testing and decision curve analysis (DCA). Additionally, we employed a Sinkhorn cost matrix to enhance interpretability. RESULTS: The proposed Sinkhorn fusion model outperformed all baseline methods, achieving the highest recall (0.96), PR-AUC (0.775), F1 score (0.828), and the best calibration (Brier score ≈ 0.19). Notably, it maintained perfect recall (1.00) under a 50% simulated modality dropout, despite a significant drop in PR-AUC (20% vs 0%: t = -20.35, P < .0001; 50% vs 0%: t = 88.60, P < .0001), portraying a strong overall robustness to information missingness. Under internally controlled conditions, DCA demonstrated superior clinical utility across thresholds of 0.2 to 0.7. CONCLUSIONS: The model's ability to accommodate unpaired and incomplete clinical inputs while maintaining both calibration and sensitivity makes it particularly well-suited for deployment in asynchronous and resource-constrained settings. Its consistent performance under clinical uncertainty and minimal preprocessing requirements represents a significant advancement toward equitable, reliable, and scalable AI-assisted breast cancer screening. To our knowledge, this is the first paper to model breast cancer late fusion as an optimal transport problem.