Automated Quantification of sTIL Density with H&E-Based Digital Image Analysis Has Prognostic Potential in Triple-Negative Breast Cancers
Open accessAbstract
Triple-negative breast cancer (TNBC) is an aggressive and difficult-to-treat cancer type that represents approximately 15% of all breast cancers. Recently, stromal tumor-infiltrating lymphocytes (sTIL) resurfaced as a strong prognostic biomarker for overall survival (OS) for TNBC patients. Manual assessment has innate limitations that hinder clinical adoption, and the International Immuno-Oncology Biomarker Working Group (TIL-WG) has therefore envisioned that computational assessment of sTIL could overcome these limitations and recommended that any algorithm should follow the manual guidelines where appropriate. However, no existing studies capture all the concepts of the guideline or have shown the same prognostic evidence as manual assessment. In this study, we present a fully automated digital image analysis pipeline and demonstrate that our hematoxylin and eosin (H&E)-based pipeline can provide a quantitative and interpretable score that correlates with the manual pathologist-derived sTIL status, and importantly, can stratify a retrospective cohort into two significant distinct prognostic groups. We found our score to be prognostic for OS (HR: 0.81 CI: 0.72–0.92 p = 0.001) independent of age, tumor size, nodal status, and tumor type in statistical modeling. While prior studies have followed fragments of the TIL-WG guideline, our approach is the first to follow all complex aspects, where appropriate, supporting the TIL-WG vision of computational assessment of sTIL in the future clinical setting.
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TME components and their interactions can influence NAC response in patients with TNBC.
“TME components and their interactions can influence NAC response in patients with TNBC [70–72].”
From Digital image analysis and machine learning-assisted prediction of neoadjuvant chemotherapy response in triple-negative breast cancer (2024) · cites this paper as [70]
The Introduction states that immune-system and tumor-microenvironment interactions play a role in clinical outcomes for patients with TNBC. It does not specifically link those interactions to neoadjuvant chemotherapy (NAC) response; the Methods (§2.1) say patients who received neoadjuvant chemotherapy were excluded. (LLM, conf=0.87)
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- Authors
- Thagaard, J., Stovgaard, E. S., Vognsen, L. G., Hauberg, S., Dahl, A., Ebstrup, T., Doré, J., Vincentz, R. E., Jepsen, R. K., Roslind, A., Kümler, I., Nielsen, D., & Balslev, E.
- Affiliations
- Technical University of Denmark (DK)
- Herlev Hospital (DK)
- Visiopharm A/S, 2970 Hørsholm, Denmark
- Corresponding author
- Thagaard, Jeppe
- ORCID
- Venue
- Cancers
- Publisher
- MDPI AG
- Published
- 2021-06-18
- Volume
- 13
- Issue
- 12
- Pages
- 3050
- ISSN
- 2072-6694 (ISSN-L)
- PMC
- PMC8235502
- OpenAlex
- W3176612188
- Cited by
- 50
- References
- 59
- Citations by year
- 2026: 6 · 2025: 15 · 2024: 10 · 2023: 12 · 2022: 7
- FWCI
- 2.56
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Cancers (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Technical University of Denmark, DTU Orbit (Technical University of Denmark, DTU) (submittedVersion, other-oa)
- Funders
- Innovationsfonden (8053-00008B)
- 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
- triple-negative breast cancer, stromal tumor-infiltrating lymphocytes, prognostic factors, overall survival, computational pathology, prognostic stratification
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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