Abstract
The eligibility for hormone therapy to treat breast cancer largely depends on the tumor’s estrogen receptor (ER) status. Recent studies show that the ER status correlates with morphological features found in Haematoxylin-Eosin (HE) slides. Thus, HE analysis might be sufficient for patients for whom the classifier confidently predicts the ER status and thereby obviate the need for additional examination, such as immunohistochemical (IHC) staining. Several prior works are limited by either the use of engineered features, multi-stage models that use features unspecific to HE images or a lack of explainability. To address these limitations, this work proposes an end-to-end neural network ensemble that shows state-of-the-art performance. We demonstrate that the approach also translates to the prediction of the cancer grade. Moreover, subsets can be selected from the test data for which the model can detect a positive ER status with a precision of 94% while classifying 13% of the patients. To compensate for the reduced interpretability of the model that comes along with end-to-end training, this work applies Layer-wise Relevance Propagation (LRP) to determine the relevant parts of the images a posteriori, commonly visualized as a heatmap overlayed with the input image. We found that nuclear and stromal morphology and lymphocyte infiltration play an important role in the classification of the ER status. This demonstrates that interpretable machine learning can be a vital tool for validating and generating hypotheses about morphological biomarkers.
Original language | English |
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Title of host publication | Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) |
Publisher | Springer |
Pages | 16-37 |
Number of pages | 22 |
DOIs | |
Publication status | Published - 2020 |
Publication series
Name | Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) |
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Volume | 12090 LNCS |
ISSN (Print) | 0302-9743 |
ISSN (Electronic) | 1611-3349 |
Bibliographical note
Publisher Copyright:© 2020, Springer Nature Switzerland AG.
Keywords
- Deep learning
- Digital pathology
- Explainable AI
ASJC Scopus subject areas
- Theoretical Computer Science
- General Computer Science