A deep learning pipeline for PAM50 subtype classification using histopathology images and multi-objective patch selection

Fuente: arXiv
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Autores principales: Borji, Arezoo, Kronreif, Gernot, Angermayr, Bernhard, Calisto, Francisco Mario, Ardakani, Ali Abbasian, Birkfellner, Wolfgang, Servetnyk, Inna, Yuan, Yinyin, Hatamikia, Sepideh
Formato: Preprint
Publicado: 2026
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author Borji, Arezoo
Kronreif, Gernot
Angermayr, Bernhard
Calisto, Francisco Mario
Ardakani, Ali Abbasian
Birkfellner, Wolfgang
Servetnyk, Inna
Yuan, Yinyin
Hatamikia, Sepideh
author_facet Borji, Arezoo
Kronreif, Gernot
Angermayr, Bernhard
Calisto, Francisco Mario
Ardakani, Ali Abbasian
Birkfellner, Wolfgang
Servetnyk, Inna
Yuan, Yinyin
Hatamikia, Sepideh
contents Breast cancer is a highly heterogeneous disease with diverse molecular profiles. The PAM50 gene signature is widely recognized as a standard for classifying breast cancer into intrinsic subtypes, enabling more personalized treatment strategies. In this study, we introduce a novel optimization-driven deep learning framework that aims to reduce reliance on costly molecular assays by directly predicting PAM50 subtypes from H&E-stained whole-slide images (WSIs). Our method jointly optimizes patch informativeness, spatial diversity, uncertainty, and patch count by combining the non-dominated sorting genetic algorithm II (NSGA-II) with Monte Carlo dropout-based uncertainty estimation. The proposed method can identify a small but highly informative patch subset for classification. We used a ResNet18 backbone for feature extraction and a custom CNN head for classification. For evaluation, we used the internal TCGA-BRCA dataset as the training cohort and the external CPTAC-BRCA dataset as the test cohort. On the internal dataset, an F1-score of 0.8812 and an AUC of 0.9841 using 627 WSIs from the TCGA-BRCA cohort were achieved. The performance of the proposed approach on the external validation dataset showed an F1-score of 0.7952 and an AUC of 0.9512. These findings indicate that the proposed optimization-guided, uncertainty-aware patch selection can achieve high performance and improve the computational efficiency of histopathology-based PAM50 classification compared to existing methods, suggesting a scalable imaging-based replacement that has the potential to support clinical decision-making.
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spellingShingle A deep learning pipeline for PAM50 subtype classification using histopathology images and multi-objective patch selection
Borji, Arezoo
Kronreif, Gernot
Angermayr, Bernhard
Calisto, Francisco Mario
Ardakani, Ali Abbasian
Birkfellner, Wolfgang
Servetnyk, Inna
Yuan, Yinyin
Hatamikia, Sepideh
Computer Vision and Pattern Recognition
Artificial Intelligence
Breast cancer is a highly heterogeneous disease with diverse molecular profiles. The PAM50 gene signature is widely recognized as a standard for classifying breast cancer into intrinsic subtypes, enabling more personalized treatment strategies. In this study, we introduce a novel optimization-driven deep learning framework that aims to reduce reliance on costly molecular assays by directly predicting PAM50 subtypes from H&E-stained whole-slide images (WSIs). Our method jointly optimizes patch informativeness, spatial diversity, uncertainty, and patch count by combining the non-dominated sorting genetic algorithm II (NSGA-II) with Monte Carlo dropout-based uncertainty estimation. The proposed method can identify a small but highly informative patch subset for classification. We used a ResNet18 backbone for feature extraction and a custom CNN head for classification. For evaluation, we used the internal TCGA-BRCA dataset as the training cohort and the external CPTAC-BRCA dataset as the test cohort. On the internal dataset, an F1-score of 0.8812 and an AUC of 0.9841 using 627 WSIs from the TCGA-BRCA cohort were achieved. The performance of the proposed approach on the external validation dataset showed an F1-score of 0.7952 and an AUC of 0.9512. These findings indicate that the proposed optimization-guided, uncertainty-aware patch selection can achieve high performance and improve the computational efficiency of histopathology-based PAM50 classification compared to existing methods, suggesting a scalable imaging-based replacement that has the potential to support clinical decision-making.
title A deep learning pipeline for PAM50 subtype classification using histopathology images and multi-objective patch selection
topic Computer Vision and Pattern Recognition
Artificial Intelligence
url https://arxiv.org/abs/2604.01798