Prediction of HER2-positive breast cancer recurrence and metastasis risk from histopathological images and clinical information via multimodal deep learning
Open accessAbstract
HER2-positive breast cancer is a highly heterogeneous tumor, and about 30% of patients still suffer from recurrence and metastasis after trastuzumab targeted therapy. Predicting individual prognosis is of great significance for the further development of precise therapy. With the continuous development of computer technology, more and more attention has been paid to computer-aided diagnosis and prognosis prediction based on Hematoxylin and Eosin (H&E) pathological images, which are available for all breast cancer patients undergone surgical treatment. In this study, we first enrolled 127 HER2-positive breast cancer patients with known recurrence and metastasis status from Cancer Hospital of the Chinese Academy of Medical Sciences. We then proposed a novel multimodal deep learning method integrating whole slide H&E images (WSIs) and clinical information to accurately assess the risk of relapse and metastasis in patients with HER2-positive breast cancer. Specifically, we obtained the whole H&E staining images from the surgical specimens of breast cancer patients, and these images were adjusted to size 512 × 512 pixels. The deep convolutional neural network (CNN) was applied to these images to retrieve image features, which were combined with the clinical data. Based on the combined features. After that, a novel multimodal model was constructed for predicting the prognosis of each patient. The model achieved an area under curve (AUC) of 0.76 in the two-fold cross-validation (CV). To further evaluate the performance of our model, we downloaded the data of all 123 HER2-positive breast cancer patients with available H&E image and known recurrence and metastasis status in The Cancer Genome Atlas (TCGA), which was severed as an independent testing data. Despite the huge differences in race and experimental strategies, our model achieved an AUC of 0.72 in the TCGA samples. As a conclusion, H&E images, in conjunction with clinical information and advanced deep learning models, could be used to evaluate the risk of relapse and metastasis in patients with HER2-positive breast cancer.
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Several studies found through ablation experiments that other fusion methods (outer product, Kronecker product, compact bilinear pooling) outperformed concatenation by a notable margin.
“However, several studies found through ablation experiments that applying other methods to fuse the feature vectors (i.e. taking the outer product, Kronecker product or compact bilinear pooling), outperformed concatenation by a notable margin Yang et al. (2022), Wang et al. (2023b, 2024c).”
From Navigating the landscape of multimodal AI in medicine: A scoping review on technical challenges and clinical applications (2025) · cites this paper as Yang et al. (2022)
The Materials and methods section ('Features fusion'; page unavailable) says outer products are more effective than concatenation and describes using multimodal compact bilinear fusion. It does not report a fusion-method ablation, quantify a margin over concatenation, or discuss Kronecker-product fusion; those parts of the claim are unsupported by this paper. (LLM, conf=0.86)
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References 44 · Cited by 233
Research works printed but not linked: 3
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- [26]Zhi W, Yueng H, Chen Z, Zandavi SM and Chung YY. The 24th International Conference On Neural Information Processing; 2017.
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- Authors
- Yang, J., Ju, J., Guo, L., Ji, B., Shi, S., Yang, Z., Gao, S., Yuan, X., Tian, G., Liang, Y., & Yuan, P.
- Affiliations
- Chifeng Municipal Hospital (CN)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Genies (Beijing) Co., Ltd., Beijing 100102, China
- Capital Medical University (CN)
- Corresponding author
- Liang, Yuebin
- Yuan, Peng
- Venue
- Computational and Structural Biotechnology Journal
- Published
- 2021-12-31
- Volume
- 20
- Pages
- 333-342
- ISSN
- 2001-0370 (ISSN-L)
- PMC
- PMC8733169
- OpenAlex
- W4200566810
- Cited by
- 233
- References
- 44
- Citations by year
- 2026: 34 · 2025: 64 · 2024: 44 · 2023: 44 · 2022: 46 · 2021: 1
- FWCI
- 11.93
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Computational and Structural Biotechnology Journal (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Chinese Academy of Medical Sciences (12019XK320071)
- Topics
- Physical Sciences › Computer Science › Artificial Intelligence › AI in cancer detection
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiomics and Machine Learning in Medical Imaging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Breast Cancer Treatment Studies
- Keywords
- HER2-positive breast cancer, breast cancer recurrence, metastasis risk prediction, outcome prediction, whole slide images, H&E staining, multimodal deep learning, clinical data integration, computer-aided diagnosis, trastuzumab, TCGA validation
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