ArticleNature2012
The clonal and mutational evolution spectrum of primary triple-negative breast cancers.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04403984 (Investigation of the Prognostic Value of Genomic Alterations or Protein Expression in Patients With Operated Early Breast Cancer of Luminal A or Luminal B Subtypes), which is not on this map. Cited by 1,141 papers, 1 of them a synthesis that pooled it.
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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.
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.
Investigation of the Prognostic Value of Genomic Alterations or Protein Expression in Patients With Operated Early Breast Cancer of Luminal A or Luminal B Subtypes
Who cites it
1,141 citing papers in PubMed, 1 synthesis or guideline pooled it, 2,008 citations in OpenAlex.
- The prognostic role of tumor mutation burden on survival of breast cancer: a systematic review and meta-analysis.BMC cancer · 2022Pooled it
- Temporal and spatial composition of the tumor microenvironment predicts response to immune checkpoint inhibition in metastatic TNBC.Nature cancer · 2026Trial
- Targeting chemotherapy resistance in mesenchymal triple-negative breast cancer: a phase II trial of neoadjuvant angiogenic and mTOR inhibition with chemotherapy.Investigational new drugs · 2023Trial
- In vivo CRISPR screening identifies metastasis suppressors in triple-negative breast cancer.Nature communications · 2026Article
- Charting intratumor heterogeneity from bench to bedside.Nature cancer · 2026Review
- Tumor evolution: signaling pathways, molecular mechanisms and therapeutic targets.Signal transduction and targeted therapy · 2026Review
- Mediator subunit MED4 enforces metastatic dormancy in breast cancer.Nature cell biology · 2026Article
- Therapeutic DC vaccination against the vascular antigen DLK1 effectively treats primary triple-negative breast cancer and prevents metastasis.NPJ vaccines · 2026Article
- 3D EM uncovers mitochondrial network remodeling in residual triple negative breast cancer after conventional chemotherapy treatments.iScience · 2026Article
- Geospatial genetic evolution and phenotypic plasticity in triple-negative breast cancer.Genome medicine · 2026Article
- A new cancer progression model: From synthetic tumors to real data and back.PLoS computational biology · 2026Article
- MEOX1 Inhibits Growth and Metastasis of Salivary Adenoid Cystic Carcinoma.Current issues in molecular biology · 2026Article
- Genetic barcoding uncovers the clonal makeup of solid and liquid biopsies and their ability to capture intra-tumoral heterogeneity.Molecular systems biology · 2026Article
- Berry-derived gold nanoparticles induce integrated ROS-mediated apoptosis, immune modulation, and transcriptomic remodeling in 4T1 triple-negative cancer cells.Cell death discovery · 2026Article
- Research Progress of PROTACs in Breast Cancer: Subtype-Oriented Target Landscape, Clinical Stratification Evidence, and Engineering Strategies for Translation.Biomedicines · 2026Review
- Patient-derived organoid xenografts reveal the multifaceted role of the lncRNAbioRxiv : the preprint server for biology · 2026Article
- Screening of kinase inhibitors in the triple negative KRAS G13D-mutated MDA-MB-231 breast cancer cell line.Scientific reports · 2026Article
- Breast cancer inequities: the intersectional role of social epidemiology and tumor biology.Cancer causes & control : CCC · 2026Review
- Comprehensive genomic profiling of triple-negative breast cancer metastases identifies role of PKD1 in immunotherapy resistance.The Journal of clinical investigation · 2026Article
- Prognostic and Diagnostic Value of Serum Bile Acid Profiles in Pancreatic Cancer: a Retrospective Multicenter Cohort Study.Journal of gastrointestinal cancer · 2026Article
1,081 more citing papers are in PubMed but not listed here.
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Authors and funding
59 authors at 10 institutions in 3 countries.
Funding
Abstract
Primary triple-negative breast cancers (TNBCs), a tumour type defined by lack of oestrogen receptor, progesterone receptor and ERBB2 gene amplification, represent approximately 16% of all breast cancers. Here we show in 104 TNBC cases that at the time of diagnosis these cancers exhibit a wide and continuous spectrum of genomic evolution, with some having only a handful of coding somatic aberrations in a few pathways, whereas others contain hundreds of coding somatic mutations. High-throughput RNA sequencing (RNA-seq) revealed that only approximately 36% of mutations are expressed. Using deep re-sequencing measurements of allelic abundance for 2,414 somatic mutations, we determine for the first time-to our knowledge-in an epithelial tumour subtype, the relative abundance of clonal frequencies among cases representative of the population. We show that TNBCs vary widely in their clonal frequencies at the time of diagnosis, with the basal subtype of TNBC showing more variation than non-basal TNBC. Although p53 (also known as TP53), PIK3CA and PTEN somatic mutations seem to be clonally dominant compared to other genes, in some tumours their clonal frequencies are incompatible with founder status. Mutations in cytoskeletal, cell shape and motility proteins occurred at lower clonal frequencies, suggesting that they occurred later during tumour progression. Taken together, our results show that understanding the biology and therapeutic responses of patients with TNBC will require the determination of individual tumour clonal genotypes.
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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.