ArticleClinical cancer research : an official journal of the American Association for Cancer Research2020
Comprehensive Profiling of Poor-Risk Paired Primary and Recurrent Triple-Negative Breast Cancers Reveals Immune Phenotype Shifts.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers, 3 of them syntheses that pooled it.
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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.
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Who cites it
74 citing papers in PubMed, 3 syntheses or guidelines pooled it, 106 citations in OpenAlex.
- Immune checkpoint inhibitors in first-line therapies of metastatic or early triple-negative breast cancer: a systematic review and network meta-analysis.Frontiers in endocrinology · 2023Pooled it
- Efficacy and safety of neoadjuvant immune checkpoint inhibitors in early-stage triple-negative breast cancer: a systematic review and meta-analysis.Journal of cancer research and clinical oncology · 2021Pooled it
- Immune Checkpoint Inhibitors Combined With Chemotherapy Compared With Chemotherapy Alone for Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- Atezolizumab and nab-Paclitaxel in Advanced Triple-Negative Breast Cancer: Biomarker Evaluation of the IMpassion130 Study.Journal of the National Cancer Institute · 2021Trial
- Trial
- The tumor microenvironment in triple negative breast cancer and a strategy to improve responses to immunotherapy using cryoablation and immunostimulants.Cancer biology & therapy · 2026Review
- Beyond conventional therapies: the evolution of targeted agents and immunotherapies in triple-negative breast cancer.Acta pharmacologica Sinica · 2026Review
- Risk stratification and relapse pattern in triple-negative breast cancer with pathological complete response after neoadjuvant treatment: the European GAMBIT real-world study.Nature communications · 2026Observational
- Genomic and transcriptomic evaluation of primary and recurrent luminal B-like breast cancer.ESMO open · 2026Article
- TNBC Spatial Transcriptomic Analysis across Clinical States Reveals Subtype-Specific Networks and Immunosuppressive Niches.Cancer research communications · 2026Article
- Clinical and histopathological characterization of metastatic lobular breast cancer: lessons learned from post-mortem tissue donation programs.NPJ breast cancer · 2026Article
- Programmable local immunochemotherapy for triple-negative breast cancer via spatiotemporally controlled release of CpG oligodeoxynucleotides, gemcitabine, and paclitaxel.NPJ breast cancer · 2026Article
- Genetically Engineered Light-Responsive In Situ Hydrogels for Immunomodulation and Multimodal Therapy in Metastatic Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- LEP and FOXO1 genes, as a proposed tumor suppressor autophagic cell death related genes, can be targeted by antidiabetic therapy in nondiabetic breast cancer patients.Discover oncology · 2025Article
- Emerging Biomarkers to Predict Immunotherapy Response in Breast Cancer.Current oncology reports · 2025Review
- Co-targeting TGF-β and PD-L1 sensitizes triple-negative breast cancer to experimental immunogenic cisplatin-eribulin chemotherapy doublet.The Journal of clinical investigation · 2025Article
- Immunotherapy and its racial specificity for breast cancer treatment in Asia: a narrative review.The Lancet regional health. Western Pacific · 2025Review
- Combination strategies with PARP inhibitors in BRCA-mutated triple-negative breast cancer: overcoming resistance mechanisms.Oncogene · 2025Review
- The evolving landscape of genetic biomarkers for immunotherapy in primary and metastatic breast cancer.Frontiers in oncology · 2025Article
- Cyclometalated iridium(III) complex based on isoquinoline alkaloid synergistically elicits the ICD response and IDO inhibitionActa pharmaceutica Sinica. B · 2025Article
14 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 5 institutions in 4 countries.
Funding
Abstract
purposeEmerging data suggest immune checkpoint inhibitors have reduced efficacy in heavily pretreated triple-negative breast cancers (TNBC), but underlying mechanisms are poorly understood. To better understand the phenotypic evolution of TNBCs, we studied the genomic and transcriptomic profiles of paired tumors from patients with TNBC. EXPERIMENTAL
designWe collected paired primary and metastatic TNBC specimens from 43 patients and performed targeted exome sequencing and whole-transcriptome sequencing. From these efforts, we ascertained somatic mutation profiles, tumor mutational burden (TMB), TNBC molecular subtypes, and immune-related gene expression patterns. Stromal tumor-infiltrating lymphocytes (stromal TIL), recurrence-free survival, and overall survival were also analyzed.
resultsWe observed a typical TNBC mutational landscape with minimal shifts in copy number or TMB over time. However, there were notable TNBC molecular subtype shifts, including increases in the Lehmann/Pietenpol-defined basal-like 1 (BL1, 11.4%-22.6%) and mesenchymal (M, 11.4%-22.6%) phenotypes, and a decrease in the immunomodulatory phenotype (IM, 31.4%-3.2%). The Burstein-defined basal-like immune-activated phenotype was also decreased (BLIA, 42.2%-17.2%). Among downregulated genes from metastases, we saw enrichment of immune-related Kyoto Encyclopedia of Genes and Genomes pathways and gene ontology (GO) terms, and decreased expression of immunomodulatory gene signatures (
conclusionsWe observed few mutational shifts, but largely consistent transcriptomic shifts in longitudinally paired TNBCs. Transcriptomic and IHC analyses revealed significantly reduced immune-activating gene expression signatures and TILs in recurrent TNBCs. These data may explain the observed lack of efficacy of immunotherapeutic agents in heavily pretreated TNBCs. Further studies are ongoing to better understand these initial observations.
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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.