Domain generalization in deep learning based mass detection in mammography: A large-scale multi-center study

Computer-aided detection systems based on deep learning have shown great potential in breast cancer detection. However, the lack of domain generalization of artificial neural networks is an important obstacle to their deployment in changing clinical environments. In this study, we explored the domain generalization of deep learning methods for mass detection in digital mammography and analyzed in-depth the sources of domain shift in a large-scale multi-center setting. To this end, we compared the performance of eight state-of-the-art detection methods, including Transformer based models, trained in a single domain and tested in five unseen domains. Moreover, a single-source mass detection training pipeline was designed to improve the domain generalization without requiring images from the new domain. The results show that our workflow generalized better than state-of-the-art transfer learning based approaches in four out of five domains while reducing the domain shift caused by the different acquisition protocols and scanner manufacturers. Subsequently, an extensive analysis was performed to identify the covariate shifts with the greatest effects on detection performance, such as those due to differences in patient age, breast density, mass size, and mass malignancy. Ultimately, this comprehensive study provides key insights and best practices for future research on domain generalization in deep learning based breast cancer detection.