Harnessing Adversarial Distillation to Customise Debiased, Disease-Specific Pathology Foundation Models for Breast Cancer
Authors: Zhiwei Chen, Yang Hu, Yuxiang Xiao, Yakun Ju, Tianyang Zhang, Yingxue Xu, Wei Li, Hao Chen, +2 more
Abstract
Pathology foundation models (PFMs) provide strong tissue representations and have become central to digital pathology. However, deployment in disease-specific settings is limited by 1) the high computational cost of billion-parameter PFMs and 2) distribution mismatch and non-biological bias inherited from pan-cancer, multi-centre pre-training, including site-specific signatures and imbalanced disease prevalence. These factors can encourage shortcut learning and under-emphasise subtle morphology required for reliable modelling of a specific cancer type. We present SmartStu (a Smart Student), a framework to customise compact, breast-cancer-specific PFMs via distillation whilst mitigating confounding. SmartStu distils representations from multiple teacher PFMs into a lightweight student backbone. Crucially, we introduce adversarial distillation that leverages a dedicated noise model trained to predict nuisance, edge-dominated cues on the distillation set. Using this noise model as a counterexample, the adversarial objective encourages the student to recognise, yet suppress, features predictive of nuisance targets. We further incorporate multi-teacher ensemble distillation and an auxiliary self-supervised objective with artefact injection. We validate SmartStu on three external cohorts (Yale HER2, SLN-Breast, and BRACS) with multiple tiny backbones. SmartStu yields breast-cancer-specific PFMs that are over 30× smaller than general PFMs whilst largely preserving, and sometimes improving, downstream performance measured by balanced accuracy (bAcc) and AUC. Code is available at https://github.com/zwchen03/advDistall.
Generalist pathology foundation models (PFMs), pretrained on large-scale multi-organ datasets, have demonstrated remarkable predictive capabilities across diverse clinical applications. However, their proficiency on the full spectrum of clinically essential tasks within a specific organ system remains an open question due to the lack of large-scale validation cohorts for a single organ as well as the absence of a tailored training paradigm that can effectively translate broad histomorphological knowledge into the organ-specific expertise required for specialist-level interpretation. In this study, we propose BRIGHT, the first PFM specifically designed for breast pathology, trained on over 51,000 breast whole-slide images derived from a cohort of over 40,000 patients across 19 hospitals. BRIGHT employs a collaborative generalist-specialist framework to capture both universal and organ-specific features. To comprehensively evaluate the performance of PFMs on breast oncology, we curate the largest multi-institutional cohorts to date for downstream task development and evaluation, comprising over 25,000 WSIs across 10 hospitals. The validation cohorts cover the full spectrum of breast pathology across 25 distinct clinical tasks spanning diagnosis, biomarker prediction, treatment response and survival prediction. Extensive experiments demonstrate that BRIGHT outperforms five leading generalist PFMs, achieving state-of-the-art (SOTA) performance in 25 of 25 internal validation tasks and in 4 of 11 external validation tasks with excellent heatmap interpretability. By evaluating on large-scale validation cohorts, this study not only demonstrates BRIGHT's clinical utility in breast oncology but also validates a collaborative generalist-specialist paradigm, providing a scalable template for developing PFMs on a specific organ system, accelerating the translation of foundation models into ...
Pathology foundation models (PFMs) have recently emerged as powerful pretrained encoders for computational pathology, enabling transfer learning across a wide range of downstream tasks. However, systematic comparisons of these models for clinically meaningful prediction problems remain limited, especially in the context of survival prediction under external validation. In this study, we benchmark widely used and recently proposed PFMs for breast cancer survival prediction from whole-slide histopathology images. Using a standardized pipeline based on patch-level feature extraction and a unified survival modeling framework, we evaluate model representations across three independent clinical cohorts comprising more than 5,400 patients with long-term follow-up. Models are trained on one cohort and evaluated on two independent external cohorts, enabling a rigorous assessment of cross-dataset generalization. Overall, H-optimus-1 achieves the strongest survival prediction performance. More broadly, we observe consistent generational improvements across model families, with second-generation PFMs outperforming their first-generation counterparts. However, absolute performance differences between many recent PFMs remain modest, suggesting diminishing returns from further scaling of pretraining data or model size alone. Notably, the compact distilled model H0-mini slightly outperforms its larger teacher model H-optimus-0, despite using fewer than 8% of the parameters and enabling significantly faster feature extraction. Together, these results provide the first large-scale, externally validated benchmark of PFMs for breast cancer survival prediction, and offer practical guidance for efficient deployment of PFMs in clinical workflows.
Fredrik K. Gustafsson, Constance Boissin, Johan Vallon-Christersson +2
Pathology foundation models (PFMs) have advanced rapidly in recent years and support training classifiers for a range of histopathology tasks. However, their robustness across hospitals remains limited: performance often degrades when training a classifier on data from one hospital and evaluating it on another target hospital. We address this challenge by fine-tuning PFMs with a local maximum mean discrepancy (LMMD) objective that applies to two settings: domain adaptation, where unlabeled target-hospital data is available, and domain generalization, where target-hospital data is unavailable at all. Experiments at both the patch- and slide-level show consistent improvements across multiple PFMs and tasks.