Prediction of Breast Cancer Recurrence Risk Using a Multi-Model Approach Integrating Whole Slide Imaging and Clinicopathologic Features

Breast cancer is the most common malignancy affecting women worldwide and is notable for its morphologic and biologic diversity, with varying risks of recurrence following treatment. The Oncotype DX Breast Recurrence Score test is an important predictive and prognostic genomic assay for estrogen receptor-positive breast cancer that guides therapeutic strategies; however, such tests can be expensive, delay care, and are not widely available. The aim of this study was to develop a multi-model approach integrating the analysis of whole slide images and clinicopathologic data to predict their associated breast cancer recurrence risks and categorize these patients into two risk groups according to the predicted score: low and high risk. The proposed novel methodology uses convolutional neural networks for feature extraction and vision transformers for contextual aggregation, complemented by a logistic regression model that analyzes clinicopathologic data for classification into two risk categories. This method was trained and tested on 993 hematoxylin and eosin-stained whole-slide images of breast cancers with corresponding clinicopathological features that had prior Oncotype DX testing. The model's performance was evaluated using an internal test set of 198 patients from Dartmouth Health and an external test set of 418 patients from the University of Chicago. The multi-model approach achieved an AUC of 0.92 (95 percent CI: 0.88-0.96) on the internal set and an AUC of 0.85 (95 percent CI: 0.79-0.90) on the external cohort. These results suggest that with further validation, the proposed methodology could provide an alternative to assist clinicians in personalizing treatment for breast cancer patients and potentially improving their outcomes.