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Analysis of institutional authors

Naranjo, ValeryAuthorMorales-Martinez, SandraAuthor

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October 23, 2025
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Article

Validation of an Artificial Intelligence Model for Breast Cancer Molecular Subtyping Using Hematoxylin and Eosin-Stained Whole-Slide Images in a Population-Based Cohort

Publicated to: Cancers. 17 (19): 1-13 - 2025-01-01 17(19), DOI: 10.3390/cancers17193234

Authors:

Kiraz, Umay; Fernández-Martín, Claudio; Rewcastle, Emma; Gudlaugsson, Einar G.; Skaland, Ivar; Naranjo Ornedo, Valeriana; Morales, Sandra; Janssen, Emiel A. M.
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Affiliations

Griffith Univ, Inst Biomed & Glyc, Southport, Qld 4215, Australia - Author
Stavanger Univ Hosp, Dept Pathol, N-4011 Stavanger, Norway - Author
Univ Politecn Valencia, HUMAN Tech, Inst Univ Invest Tecnol Centrada Ser Humano, Valencia 46022, Spain - Author
Univ Stavanger, Dept Chem Biosci & Environm Engn, N-4021 Stavanger, Norway - Author
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Abstract

Simple Summary Breast cancer is a complex disease that can be classified into different biological subtypes. Correctly identifying these subtypes is essential in determining the most effective treatment for each patient. However, current methods such as gene expression testing and immunohistochemistry are either expensive, time-consuming, or not widely available in all healthcare settings. In this study, we explored whether a computer-based approach using artificial intelligence can accurately predict breast cancer subtypes by analyzing routine pathology slides stained with hematoxylin and eosin. This real-world validation study shows that this method can identify certain subtypes with promising accuracy, offering a faster and more accessible alternative to existing techniques. This research may help improve diagnostic processes, especially in hospitals with limited resources, and support more personalized treatment decisions for patients with breast cancer.Abstract Background/Objectives: Breast cancer (BC) is the most commonly diagnosed cancer in women and the leading cause of cancer-related deaths globally. Molecular subtyping is crucial for prognosis and treatment planning, with immunohistochemistry (IHC) being the most commonly used method. However, IHC has limitations, including observer variability, a lack of standardization, and a lack of reproducibility. Gene expression profiling is considered the ground truth for molecular subtyping; unfortunately, this is expensive and inaccessible to many institutions. This study investigates the potential of an artificial intelligence (AI) model to predict BC molecular subtypes directly from hematoxylin and eosin (H&E)-stained whole-slide images (WSIs). Methods: A pretrained deep learning framework based on multiple-instance learning (MIL) was validated on the Stavanger Breast Cancer (SBC) dataset, consisting of 538 BC cases. Three classification tasks were assessed, including two-class [triple negative BC (TNBC) vs. non-TNBC], three-class (luminal vs. HER2-positive vs. TNBC), and four-class (luminal A vs. luminal B vs. HER2-positive vs. TNBC) groups. Performance metrics were used for the evaluation of the AI model. Results: The AI model demonstrated strong performance in distinguishing TNBC from non-TNBC (AUC = 0.823, accuracy = 0.833, F1-score = 0.824). However, performance declined with an increasing number of classes. Conclusions: The study highlights the potential of AI in BC molecular subtyping from H&E WSIs, offering an easily applicable and standardized method to IHC. Future improvements should focus on optimizing multi-class classification and validating AI-based methods against gene expression analyses for enhanced clinical applicability.
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Keywords

Breast cancerComputational pathologyDeep learningHematoxylin and eosin-stainedMolecular subtype predictionWhole-slide images

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Cancers due to its progression and the good impact it has achieved in recent years, according to the agency Scopus (SJR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position , thus managing to position itself as a Q1 (Primer Cuartil), in the category Oncology.

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Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-04-03:

  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 10 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

    It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

    • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
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    Leadership analysis of institutional authors

    This work has been carried out with international collaboration, specifically with researchers from: Australia; Norway.

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    Awards linked to the item

    This work was funded by the Horizon 2020 European Union research and innovation program under the Marie Sklodowska Curie grant agreement No 860627 (CLARIFY Project). This work was partially funded by Ayuda a Primeros Proyectos de Investigacion (PAID-06-23), Vicerrectorado de Investigacion of the Universitat Politecnica de Valencia.
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