External Validation of Deep Learning Models for BI-RADS Breast Density Prediction from Ultrasound Images
Authors: Yuxuan Chen, Arianna Bunnell, Yanqi Xu, Haoyan Yang, Thomas K. Wolfgruber, John A. Shepherd, Yiqiu Shen
Organizations: aPerlmutter Cancer Center, NYU Langone Health, New York, NY, USA · cUniversity of Hawai’i Cancer Center, Honolulu, HI, USA · dUniversity of Hawai’i at M¯anoa, Honolulu, HI, USA · eCenter for Data Science, New York University, New York, NY, USA · fDepartment of Computer Science, Stony Brook University, Stony Brook, NY, USA · bDepartment of Radiology, NYU Langone Health, New York, NY, USA
We externally validated three deep learning models (DenseNet121, ViT-B/32, and ResNet50) for predicting mammographic breast density from breast ultrasound exams on an independent cohort. The external validation set comprised 2,000 ultrasound exams, including 500 cancer cases defined by an initial negative exam (BI-RADS 1 or 2) followed by a cancer diagnosis within 6 months to 10 years, and 1,500 negative controls matched by manufacturer and study year. Performance was measured using patient-level AUROC across four density categories: A (fatty), B (scattered), C (heterogeneous), and D (extremely dense). As a downstream assessment, we also evaluated 10-year risk prediction by incorporating age and AI-derived density into the Tyrer-Cuzick model and comparing performance against a reference model using age and mammography-reported density. All three models performed best in extremely dense breasts (AUROC 0.868-0.899), with strong performance in fatty (0.814-0.838) and scattered density (0.764-0.799), and lower performance in heterogeneously dense breasts (0.699-0.729). DenseNet121 achieved the highest overall performance (micro-averaged AUROC 0.885), and performance across categories was comparable between internal and external testing. For risk modeling, age combined with AI-derived density yielded a lower AUROC than age combined with mammography-reported density (0.541 vs. 0.570; p = 0.23), with no statistically significant difference. These findings indicate that deep learning models generalize well to external data with different racial composition for breast density assessment. While performance is strongest in extremely dense breasts, heterogeneously dense remains more challenging, highlighting the need for targeted optimization.
We present Aegis, a joint-embedding predictive architecture for breast cancer detection and density assessment in mammography. We train three Vision Transformer variants (Small/Base/Large) using self-supervised joint-embedding predictive architecture (JEPA) pre-training on 71,103 studies from 14 clinical sites, followed by supervised fine-tuning with progressive resolution scaling up to 2048x1536. On a curated 785-study test set, our largest model achieves area under the receiver operating characteristic curve (AUC) 0.949 for breast cancer triage with 93% sensitivity and 75% specificity at the optimal operating point. An ensemble combining our model with a U.S. Food and Drug Administration-cleared baseline further improves discrimination to 0.952 AUC. For breast density classification, the model achieves 0.953 AUC for binary (dense vs. non-dense) classification and 62.6% exact accuracy across four Breast Imaging Reporting and Data System (BI-RADS) categories, with 98.8% adjacent accuracy comparable to reported human inter-reader agreement. External validation on the public VinDr-Mammo dataset provides evidence of cross-population transfer under a different reference standard, with the largest model achieving 0.871 AUC for triage in a zero-shot setting.
Scott Chase Waggener, Sai Karthik Navuluru, Lakshman Tamil
Breast density classification is a critical component of breast cancer risk assessment, yet AI models often struggle to generalize across clinical sites due to vendor-specific acquisition styles. In this work, we introduce two new datasets, BreastMammo and DenseMammo, to facilitate robust multi-view mammography research. We propose a domain generalization framework that utilizes a foreground-only histogram matching protocol to resolve the domain shift issue arising from disparate clinical sources. Internal evaluation using a 5-fold cross-validation protocol demonstrates the efficacy of our approach, with the Swin Transformer backbone achieving a peak AUC of 98.32% for density classification. External evaluation on the TNMammo and LUMINA datasets demonstrates that the proposed approach consistently reduces domain shift, significantly outperforming prominent domain generalization paradigms, including MixStyle and Discrete-Fourier-Transform-based frameworks.
Hongyi Pan, Gorkem Durak, Halil Ertugrul Aktas +18
Mammogram-based deep learning models have improved breast cancer risk prediction, but the learned imaging patterns remain underexplored. Existing interpretability methods rely on single-image saliency maps, failing to identify recurring mammographic phenotypes across large patient cohorts. By clustering patch embeddings from a pre-trained model, Mirai, we isolate recurring phenotypes linked to 5-year cancer risk. Analyses show risk-increasing phenotypes capture complex structures (e.g., dense tissue, microcalcifications) and shortcut artifacts (e.g., clips). These phenotypes correlate strongly with older age and higher BI-RADS density. Our framework connects tissue patterns to AI risk scores, revealing clinical signatures and potential latent model confounders.