Ensemble-based deep learning improves detection of invasive breast cancer in routine histopathology images

Accurate detection of invasive breast cancer (IC) can provide decision support to pathologists as well as improve downstream computational analyses, where detection of IC is a first step. Tissue containing IC is characterized by the presence of specific morphological features, which can be learned by convolutional neural networks (CNN). Here, we compare the use of a single CNN model versus an ensemble of several base models with the same CNN architecture, and we evaluate prediction performance as well as variability across ensemble based model predictions. Two in-house datasets comprising 587 whole slide images (WSI) are used to train an ensemble of ten InceptionV3 models whose consensus is used to determine the presence of IC. A novel visualisation strategy was developed to communicate ensemble agreement spatially. Performance was evaluated in an internal test set with 118 WSIs, and in an additional external dataset (TCGA breast cancer) with 157 WSI. We observed that the ensemble-based strategy outperformed the single CNN-model alternative with respect to accuracy on tile level in 89 % of all WSIs in the test set. The overall accuracy was 0.92 (DICE coefficient, 0.90) for the ensemble model, and 0.85 (DICE coefficient, 0.83) for the single CNN alternative in the internal test set. For TCGA the ensemble outperformed the single CNN in 96.8 % of the WSI, with an accuracy of 0.87 (DICE coefficient 0.89), the single model provides an accuracy of 0.75 (DICE coefficient 0.78). The results suggest that an ensemble-based modeling strategy for breast cancer invasive cancer detection consistently outperforms the conventional single model alternative. Furthermore, visualisation of the ensemble agreement and confusion areas provide direct visual interpretation of the results. High performing cancer detection can provide decision support in the routine pathology setting as well as facilitate downstream computational analyses.