Computational Pathology for Accurate Prediction of Breast Cancer Recurrence: Development and Validation of a Deep Learning-based Tool.

Accurate recurrence risk stratification is crucial for optimizing treatment plans for breast cancer patients. Current prognostic tools like Oncotype DX (ODX) offer valuable genomic insights for HR+/HER2- patients but are limited by cost and accessibility, particularly in underserved populations. In this study, we present Deep-BCR-Auto, a deep learning-based computational pathology approach that predicts breast cancer recurrence risk from routine H&E-stained whole slide images (WSIs). Our methodology was validated on two independent cohorts: the TCGA-BRCA dataset and an in-house dataset from The Ohio State University (OSU). Deep-BCR-Auto demonstrated robust performance in stratifying patients into low- and high-recurrence risk categories. On the TCGA-BRCA dataset, the model achieved an area under the receiver operating characteristic curve (AUROC) of 0.827, significantly outperforming existing weakly supervised models (p=0.041). In the independent OSU dataset, Deep-BCR-Auto maintained strong generalizability, achieving an AUROC of 0.832, along with 82.0% accuracy, 85.0% specificity, and 67.7% sensitivity. These findings highlight the potential of computational pathology as a cost-effective alternative for recurrence risk assessment, broadening access to personalized treatment strategies. This study underscores the clinical utility of integrating deep learning-based computational pathology into routine pathological assessment for breast cancer prognosis across diverse clinical settings.