ArticleBreast cancer research : BCR2025
Intra-tumoral spatial heterogeneity in breast cancer quantified using high-dimensional protein multiplexing and single cell phenotyping.
Article in Breast cancer research : BCR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed.
- Traditional Chinese Medicine Combined With Chemotherapy for Mammary Paget's Disease With Multifocal Heterogeneous Breast Cancer: A Case Report.Clinical case reports · 2026Article
- 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 · 2026Review
- Sequential MALDI-MSI-Based Multiomics Reveals Spatial Lipid, Glycan, and Tryptic Peptide Signatures in Breast Tumor Histopathology.Analytical chemistry · 2026Article
- Evaluating immunoreactivity of hybridoma-derived antibody mixtures generated against AU-565 cell line for diagnosis and immunotherapy of breast cancer.BMC cancer · 2026Article
- Article
- Context-dependent MAN1A1 protein expression in metastatic breast cancer progression predicts patient survival.BMC cancer · 2025Article
- Emerging Breast Cancer Subpopulations: Functional Heterogeneity Beyond the Classical Subtypes.International journal of molecular sciences · 2025Review
- The Trojan Horse Within: Mechanisms of Immune Evasion in Breast Cancer.Cancer heterogeneity and plasticity · 2025Article
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Abstract
backgroundBreast cancer is a highly heterogeneous disease where variations of biomarker expression may exist between individual foci of a cancer (intra-tumoral heterogeneity). The extent of variation of biomarker expression in the cancer cells, distribution of cell types in the local tumor microenvironment and their spatial arrangement could impact on diagnosis, treatment planning and subsequent response to treatment.
methodsUsing quantitative multiplex immunofluorescence (MxIF) imaging, we assessed the level of variations in biomarker expression levels among individual cells, density of cell cluster groups and spatial arrangement of immune subsets from regions sampled from 38 multi-focal breast cancers that were processed using whole-mount histopathology techniques. Molecular profiling was conducted to determine the intrinsic molecular subtype of each analysed region.
resultsA subset of cancers (34.2%) showed intra-tumoral regions with more than one molecular subtype classification. High levels of intra-tumoral variations in biomarker expression levels were observed in the majority of cancers studied, particularly in Luminal A cancers. HER2 expression quantified with MxIF did not correlate well with HER2 gene expression, nor with clinical HER2 scores. Unsupervised clustering revealed the presence of various cell clusters with unique IHC4 protein co-expression patterns and the composition of these clusters were mostly similar among intra-tumoral regions. MxIF with immune markers and image patch analysis classified immune niche phenotypes and the prevalence of each phenotype in breast cancer subtypes was illustrated.
conclusionsOur work illustrates the extent of spatial heterogeneity in biomarker expression and immune phenotypes, and highlights the importance of a comprehensive spatial assessment of the disease for prognosis and treatment planning.
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