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Updated: Sep 18, 2025

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Quantification of Breast Cancer Cell Invasiveness Using a Three-dimensional 3D Model
Published on: June 11, 2014
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Multi-site validation of an interpretable model to analyze breast masses
Luke Moffett1, Alina Jade Barnett1, Jon Donnelly1
1Department of Computer Science, Duke University, Durham, North Carolina, United States of America.
Plos One
|June 26, 2025
Summary
This study validated an interpretable deep learning model for breast lesion malignancy prediction. While performance slightly decreased externally, the model
Area of Science:
- Medical Imaging
- Artificial Intelligence
- Oncology
Background:
- Deep learning models show promise in breast lesion malignancy prediction.
- Interpretability in AI models is crucial for clinical trust and adoption.
- External validation is essential to assess model generalizability.
Purpose of the Study:
- To perform the first external validation of IAIA-BL, a deep learning-based, inherently interpretable breast lesion malignancy prediction model.
- To assess the generalizability of both performance and interpretability of IAIA-BL on external patient cohorts.
- To compare IAIA-BL against black-box baseline models in external validation settings.
Main Methods:
- External validation of the IAIA-BL model on two independent patient datasets (iCAD and Emory University).
- Evaluation of mass margin and malignancy classification performance using Area Under the Curve (AUC).
- Assessment of model interpretability through analysis of model activation on relevant lesion areas.
Main Results:
- IAIA-BL exhibited decreased mass margin classification performance on external datasets compared to the internal dataset, as measured by AUC.
- Malignancy classification performance also showed a reduction, but AUC 95% confidence intervals overlapped across all sites.
- Model interpretability, indicated by activation on relevant lesion portions, was maintained across all tested patient populations.
Conclusions:
- Model interpretability demonstrated generalizability across external datasets, even when classification performance experienced a slight decline.
- This study highlights the potential for interpretable AI models in breast cancer diagnostics to maintain transparency in real-world clinical settings.
- The findings support the development of inherently interpretable AI tools for reliable breast lesion assessment.

