Deep learning models for histologic grading of breast cancer and association with disease prognosis

Abstract

Histologic grading of breast cancer involves review and scoring of three well-established morphologic features: mitotic count, nuclear pleomorphism, and tubule formation. Taken together, these features form the basis of the Nottingham Grading System which is used to inform breast cancer characterization and prognosis. In this study, we develop deep learning models to perform histologic scoring of all three components using digitized hematoxylin and eosin-stained slides containing invasive breast carcinoma. We first evaluate model performance using pathologist-based reference standards for each component. To complement this typical approach to evaluation, we further evaluate the deep learning models via prognostic analyses. The individual component models perform at or above published benchmarks for algorithm-based grading approaches, achieving high concordance rates with pathologist grading. Further, prognostic performance using deep learning-based grading is on par with that of pathologists performing review of matched slides. By providing scores for each component feature, the deep-learning based approach also provides the potential to identify the grading components contributing most to prognostic value. This may enable optimized prognostic models, opportunities to improve access to consistent grading, and approaches to better understand the links between histologic features and clinical outcomes in breast cancer.