Abstract:Background: Mammographic breast density, as defined by the American College of Radiology's Breast Imaging Reporting and Data System (BI-RADS), is one of the strongest risk factors for breast cancer, but is derived from mammographic images. Breast ultrasound (BUS) is an alternative breast cancer screening modality, particularly useful for early detection in low-resource, rural contexts. The purpose of this study was to explore an artificial intelligence (AI) model to predict BI-RADS mammographic breast density category from clinical, handheld BUS imaging. Methods: All data are sourced from the Hawaii and Pacific Islands Mammography Registry. We compared deep learning methods from BUS imaging, as well as machine learning models from image statistics alone. The use of AI-derived BUS density as a risk factor for breast cancer was then compared to clinical BI-RADS breast density while adjusting for age. The BUS data were split by individual into 70/20/10% groups for training, validation, and testing. Results: 405,120 clinical BUS images from 14.066 women were selected for inclusion in this study, resulting in 9.846 women for training (302,574 images), 2,813 for validation (11,223 images), and 1,406 for testing (4,042 images). On the held-out testing set, the strongest AI model achieves AUROC 0.854 predicting BI-RADS mammographic breast density from BUS imaging and outperforms all shallow machine learning methods based on image statistics. In cancer risk prediction, age-adjusted AI BUS breast density predicted 5-year breast cancer risk with 0.633 AUROC, as compared to 0.637 AUROC from age-adjusted clinical breast density. Conclusions: BI-RADS mammographic breast density can be estimated from BUS imaging with high accuracy using a deep learning model. Furthermore, we demonstrate that AI-derived BUS breast density is predictive of 5-year breast cancer risk in our population.