# Investigating the Impact of Histopathological Foundation Models on Regressive Prediction of Homologous Recombination Deficiency

arXiv: https://arxiv.org/abs/2602.00151 · HTML: https://mlsanity.com/paper/2602.00151/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 10 of its 29 references that are in the map.
- First posted on arXiv 29 Jan 2026.

## Builds on (most cited first, 10 of 10)

- [Language Models are Few-Shot Learners](https://mlsanity.com/paper/2005.14165/) (2020)
- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Robust Speech Recognition via Large-Scale Weak Supervision](https://mlsanity.com/paper/2212.04356/) (2022)
- [On the Opportunities and Risks of Foundation Models](https://mlsanity.com/paper/2108.07258/) (2021)
- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [TransMIL: Transformer based Correlated Multiple Instance Learning for Whole Slide Image Classification](https://mlsanity.com/paper/2106.00908/) (2021)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [DeepSMILE: Contrastive self-supervised pre-training benefits MSI and HRD classification directly from H&E whole-slide images in colorectal and breast cancer](https://mlsanity.com/paper/2107.09405/) (2021)
- [A Survey of Pathology Foundation Model: Progress and Future Directions](https://mlsanity.com/paper/2504.04045/) (2025)
- [Regression-based Deep-Learning predicts molecular biomarkers from pathology slides](https://mlsanity.com/paper/2304.05153/) (2023)

## Abstract (arXiv)

Foundation models pretrained on large-scale histopathology data have found great success in various fields of computational pathology, but their impact on regressive biomarker prediction remains underexplored. In this work, we systematically evaluate histopathological foundation models for regression-based tasks, demonstrated through the prediction of homologous recombination deficiency (HRD) score - a critical biomarker for personalized cancer treatment. Within multiple instance learning frameworks, we extract patch-level features from whole slide images (WSI) using five state-of-the-art foundation models, and evaluate their impact compared to contrastive learning-based features. Models are trained to predict continuous HRD scores based on these extracted features across breast, endometrial, and lung cancer cohorts from two public medical data collections. Extensive experiments demonstrate that models trained on foundation model features consistently outperform the baseline in terms of predictive accuracy and generalization capabilities while exhibiting systematic differences among the foundation models. Additionally, we propose a distribution-based upsampling strategy to mitigate target imbalance in these datasets, significantly improving the recall and balanced accuracy for underrepresented but clinically important patient populations. Furthermore, we investigate the impact of different sampling strategies and instance bagsizes by ablation studies. Our results highlight the benefits of large-scale histopathological pretraining for more precise and transferable regressive biomarker prediction, showcasing its potential to advance AI-driven precision oncology.