ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
High Intratumoral Stromal Content Defines Reactive Breast Cancer as a Low-risk Breast Cancer Subtype.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 33 citations in OpenAlex.
- Prognostic and predictive impact of stroma cells defined by PDGFRb expression in early breast cancer: results from the randomized SweBCG91RT trial.Breast cancer research and treatment · 2021Trial
- Spatial organization of the tumor-immune microenvironment in ER-positive breast cancer: remodeling during treatment and associations with clinical response.bioRxiv : the preprint server for biology · 2025Article
- The Variety of 3D Breast Cancer Models for the Study of Tumor Physiology and Drug Screening.International journal of molecular sciences · 2023Review
- The Great Immune Escape: Understanding the Divergent Immune Response in Breast Cancer Subtypes.Cancer discovery · 2023Review
- Impact of Cuproptosis-related markers on clinical status, tumor immune microenvironment and immunotherapy in colorectal cancer: A multi-omic analysis.Computational and structural biotechnology journal · 2023Article
- Proteomic analysis of archival breast cancer clinical specimens identifies biological subtypes with distinct survival outcomes.Nature communications · 2022Article
- Article
- Roles of the Immune/Methylation/Autophagy Landscape on Single-Cell Genotypes and Stroke Risk in Breast Cancer Microenvironment.Oxidative medicine and cellular longevity · 2021Article
- Tumour Stroma Ratio Assessment Using Digital Image Analysis Predicts Survival in Triple Negative and Luminal Breast Cancer.Cancers · 2020Article
- Development of Radiotracers for Breast Cancer-The Tumor Microenvironment as an Emerging Target.Cells · 2020Review
- Epigenetic Reprogramming of Cancer-Associated Fibroblasts Deregulates Glucose Metabolism and Facilitates Progression of Breast Cancer.Cell reports · 2020Article
- Alterations in Immune-Related Genes as Potential Marker of Prognosis in Breast Cancer.Frontiers in oncology · 2020Article
- Immune and Stroma Related Genes in Breast Cancer: A Comprehensive Analysis of Tumor Microenvironment Based on the Cancer Genome Atlas (TCGA) Database.Frontiers in medicine · 2020Article
- p62-DNA-encoding plasmid reverts tumor grade, changes tumor stroma, and enhances anticancer immunity.Aging · 2019Article
- Breast cancer quantitative proteome and proteogenomic landscape.Nature communications · 2019Article
- ColXα1 is a stromal component that colocalizes with elastin in the breast tumor extracellular matrix.The journal of pathology. Clinical research · 2019Article
- Identification of a five-lncRNA signature for predicting the risk of tumor recurrence in patients with breast cancer.International journal of cancer · 2018Article
- Cdh1 and Pik3ca Mutations Cooperate to Induce Immune-Related Invasive Lobular Carcinoma of the Breast.Cell reports · 2018Article
- Personalized regression enables sample-specific pan-cancer analysis.Bioinformatics (Oxford, England) · 2018Article
- Proteomic Features of Colorectal Cancer Identify Tumor Subtypes Independent of Oncogenic Mutations and Independently Predict Relapse-Free Survival.Annals of surgical oncology · 2017Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
purposeThe current study evaluated associative effects of breast cancer cells with the tumor microenvironment and its influence on tumor behavior. EXPERIMENTAL
designFormalin-fixed, paraffin-embedded tissue and matched protein lysates were evaluated from two independent breast cancer patient datasets (TCGA and MD Anderson). Reverse-phase protein arrays (RPPA) were utilized to create a proteomics signature to define breast tumor subtypes. Expression patterns of cell lines and normal breast tissues were utilized to determine markers that were differentially expressed in stroma and cancer cells. Protein localization and stromal contents were evaluated for matched cases by imaging.
resultsA subtype of breast cancers designated "Reactive," previously identified by RPPA that was not predicted by mRNA profiling, was extensively characterized. These tumors were primarily estrogen receptor (ER)-positive/human EGF receptor (HER)2-negative, low-risk cancers as determined by enrichment of low-grade nuclei, lobular or tubular histopathology, and the luminal A subtype by PAM50. Reactive breast cancers contained high numbers of stromal cells and the highest extracellular matrix content typically without infiltration of immune cells. For ER-positive/HER2-negative cancers, the Reactive classification predicted favorable clinical outcomes in the TCGA cohort (HR, 0.36; P < 0.05).
conclusionsA protein stromal signature in breast cancers is associated with a highly differentiated phenotype. The stromal compartment content and proteins are an extended phenotype not predicted by mRNA expression that could be utilized to subclassify ER-positive/HER2-negative breast cancers. Clin Cancer Res; 22(20); 5068-78. ©2016 AACR.
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