ArticleJCO precision oncology2022
Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit.
Article in JCO precision oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 41 citations in OpenAlex.
- Carboplatin with or without nivolumab in metastatic triple-negative breast cancer: a randomized phase II trial.Nature communications · 2026Trial
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- Tumor genomics in patients younger than 40 years of age with metastatic breast cancer.NPJ precision oncology · 2026Article
- LKB1 dictates sensitivity to immunotherapy through Skp2-mediated ubiquitination of immune checkpoint proteins in HCC with python analysis.Iranian journal of basic medical sciences · 2026Article
- Expression of carcinoma ecotypes in the tumor microenvironment predicts response to neoadjuvant therapy in early-stage breast cancer.Scientific reports · 2025Article
- AMPK-a key factor in crosstalk between tumor cell energy metabolism and immune microenvironment?Cell death discovery · 2024Review
- Article
- Immune micro-environment analysis and establishment of response prediction model for PD-1 blockade immunotherapy in glioblastoma based on transcriptome deconvolution.Journal of cancer research and clinical oncology · 2023Article
- Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Where Are We Now and Where Are We Headed?Current treatment options in oncology · 2023Review
- Article
- The interplay between eosinophils and T cells in breast cancer immunotherapy.Molecular oncology · 2023Article
Corrections and comments
- Erratum issuedErratum.2023
Authors and funding
26 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeIn metastatic triple-negative breast cancer (mTNBC), consistent biomarkers of immune checkpoint inhibitor (ICI) therapy benefit remain elusive. We evaluated the immune, genomic, and transcriptomic landscape of mTNBC in patients treated with ICIs.
methodsWe identified 29 patients with mTNBC treated with pembrolizumab or atezolizumab, either alone (n = 9) or in combination with chemotherapy (n = 14) or targeted therapy (n = 6), who had tumor tissue and/or blood available before ICI therapy for whole-exome sequencing. RNA sequencing and CIBERSORTx-inferred immune population analyses were performed (n = 20). Immune cell populations and programmed death-ligand 1 expression were assessed using multiplexed immunofluorescence (n = 18). Clonal trajectories were evaluated via serial tumor/circulating tumor DNA whole-exome sequencing (n = 4). Association of biomarkers with progression-free survival and overall survival (OS) was assessed.
resultsProgression-free survival and OS were longer in patients with high programmed death-ligand 1 expression and tumor mutational burden. Patients with longer survival also had a higher relative inferred fraction of CD8+ T cells, activated CD4+ memory T cells, M1 macrophages, and follicular helper T cells and enrichment of inflammatory gene expression pathways. A mutational signature of defective repair of DNA damage by homologous recombination was enriched in patients with both shorter OS and primary resistance. Exploratory analysis of clonal evolution among four patients treated with programmed cell death protein 1 blockade and a tyrosine kinase inhibitor suggested that clonal stability post-treatment was associated with short time to progression.
conclusionThis study identified potential biomarkers of response to ICIs among patients with mTNBC: high tumor mutational burden; presence of CD8+, CD4 memory T cells, follicular helper T cells, and M1 macrophages; and inflammatory gene expression pathways. Pretreatment deficiencies in the homologous recombination DNA damage repair pathway and the absence of or minimal clonal evolution post-treatment may be associated with worse outcomes.
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