Evidence map›Paper›PMID 39956271›Full record

ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2025

Genomic Characteristics Related to Histology-Based Immune Features in Breast Cancer.

Yoon Jin Cha, Constandina E O'Connell, Benjamin C Calhoun, Brooke M Felsheim, Aranzazu Fernandez-Martinez, Cheng Fan, Christian Brueffer, Christer Larsson, Åke Borg, Lao H Saal and 1 more

Abstract read
In one paragraph

Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
  2. Article
  3. Decoding the breast cancer microenvironment by spatial multi-omics: from architecture to clinical translation.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  4. Article
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  7. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Yoon Jin ChaDepartment of Pathology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Constandina E O'ConnellDepartment of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Benjamin C CalhounDepartment of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Brooke M FelsheimLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Bioinformatics and Computational Biology Curriculum, Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Aranzazu Fernandez-MartinezDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Drug Development Department (DITEP), Gustave Roussy Cancer Campus, Villejuif, France; Inserm, Gustave Roussy Cancer Campus, UMR981, Villejuif, France.
Cheng FanLineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
Christian BruefferDivision of Oncology, Department of Clinical Sciences, Lund University, Sweden; Lund University Cancer Center, Lund University, Sweden; Skåne University Hospital Comprehensive Cancer Center, Lund, Sweden.
Christer LarssonLund University Cancer Center, Lund University, Sweden; Skåne University Hospital Comprehensive Cancer Center, Lund, Sweden; Division of Translational Cancer Research, Department of Laboratory Medicine, Lund University, Sweden.
Åke BorgDivision of Oncology, Department of Clinical Sciences, Lund University, Sweden; Lund University Cancer Center, Lund University, Sweden; Skåne University Hospital Comprehensive Cancer Center, Lund, Sweden.
Lao H SaalDivision of Oncology, Department of Clinical Sciences, Lund University, Sweden; Lund University Cancer Center, Lund University, Sweden; Skåne University Hospital Comprehensive Cancer Center, Lund, Sweden.
Charles M PerouDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Pathology and Laboratory Medicine, University of North Carolina School of Medicine, Chapel Hill, North Carolina; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. Electronic address: cperou@med.unc.edu.

Funding

Tissue Procurement & PathologyP50CA058223 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI CHARLES M PEROU · 1992 to 2026
$59.3M
Predoctoral Training Program in Bioinformatics and Computational BiologyT32GM135123 · NIGMS · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Michael Isaiah Love, William Valdar · 2021 to 2026
$1.7M
Characterizing and Overcoming MHC-I-Mediated Immune Evasion in Triple-Negative Breast CancerF31CA290953 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI O'CONNELL, DINA · 2024 to 2025
$81k
NCI NIH HHS F31 CA290953NCI NIH HHS P50 CA058223NIGMS NIH HHS T32 GM135123
6 · The paper itself

Abstract

The immune cell component of the tumor microenvironment is an important modulator of tumor progression. In patients with breast cancer, tumor-infiltrating lymphocytes (TILs) and tertiary lymphoid structures (TLS) represent core aspects of antitumor immunity, both increasingly recognized for clinical relevance. In this study, we evaluated immune-related histology features using whole-slide hematoxylin and eosin (H&E) images of The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data set (n = 1035) and analyzed these distinct features relative to gene expression, PAM50 subtypes, and patient survival. H&E images were evaluated for TILs, plasma cells (PCs), high-endothelial venule-associated lymphoid aggregates (HALA), and mature TLS. For HALA and TLS, location relative to the tumor (nontumor, peritumor, and intratumor) was determined. HER2-enriched (HER2E) and basal-like breast tumors exhibited the highest mean TILs and the presence of PCs. HALA were present in 35.1% of cases and TLS in 6.5% of cases, also predominantly in HER2E and basal-like tumors. We derived gene expression signatures for 10 histologically defined immune features and tested their clinical significance using transcriptomic and survival data from the Sweden Cancerome Analysis Network - Breast (SCAN-B) cohort. Signatures related to TILs, PCs, HALA/TLS, TLS, and specifically intratumor HALA and TLS were associated with better survival in HER2E and basal-like tumors. Peritumor HALA/TLS and nontumor signatures were nonsignificant or associated with worse outcomes. Furthermore, we compared the immune microenvironment of high-TIL (TILs > 10%) tumors from TCGA-BRCA by PAM50 subtype through supervised analyses of 200+ immune gene expression signatures, and unique immune features were identified for each subtype. In high-TIL luminal tumors, enriched immune signatures had little relation to prognosis. High-TIL HER2E and basal-like tumors had distinct immune signatures linked to improved survival, related to B and T cells, respectively. Overall, PAM50 subtypes of breast cancer exhibit distinct immune microenvironments, both histologically and molecularly. These differences in immune properties should be considered when developing precise treatment strategies to achieve optimal therapeutic efficacy for patients.

Indexed as

Biomarkers, TumorBreast NeoplasmsLymphocytes, Tumor-InfiltratingTertiary Lymphoid StructuresTumor MicroenvironmentFemaleGenomicsHumansMiddle AgedBiomarkers, Tumorbreast cancerPAM50 subtypeRNA sequencingtertiary lymphoid structurestumor-infiltrating lymphocytestumor microenvironment

Identifiers

PMID39956271
PMCPMC12103273

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.