ArticleNature genetics2013
ESR1 ligand-binding domain mutations in hormone-resistant breast cancer.
Article in Nature genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 720 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
A Phase II Study of Pembrolizumab And Tamoxifen Among Women With Advanced Hormone Receptor Positive Breast Cancer And Esr1 Mutation
Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA
Who cites it
720 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,235 citations in OpenAlex.
- Dynamic circulating tumor DNA profiling of ESR1 mutations in HR+/HER2- advanced breast cancer: from prognostic biomarker to clinical decision-making - a comprehensive review.Frontiers in oncology · 2026Pooled it
- SEOM-GEICAM-SOLTI clinical guidelines in advanced breast cancer (UPDATE 2025).Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Guideline
- Assessing endocrine resistance: monitoring circulating ESR1 mutations in Irosustat-treated ER positive breast cancer.Breast cancer research and treatment · 2025Trial
- A predictive endocrine resistance index accurately stratifies luminal breast cancer treatment responders and nonresponders.The Journal of clinical investigation · 2025Trial
- Transcriptomic Predictors of Survival for Palbociclib + Endocrine Therapy Versus Capecitabine in Aromatase Inhibitor-Resistant Breast Cancer From the GEICAM/2013-02 PEARL Trial.JCO precision oncology · 2025Trial
- Palazestrant, a novel oral Complete Estrogen Receptor Antagonist (CERAN) and Selective Estrogen Receptor Degrader (SERD), in patients with ER+/HER2- advanced or metastatic breast cancer: phase 1/2 study results.Breast cancer research : BCR · 2025Trial
- A Phase II Study of Fulvestrant plus Abemaciclib in Hormone Receptor-Positive Advanced or Recurrent Endometrial Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Elacestrant in Women with Estrogen Receptor-Positive and HER2-Negative Early Breast Cancer: Results from the Preoperative Window-of-Opportunity ELIPSE Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Exploring the role of ESR1 mutations in metastatic hormone receptor-positive breast cancer T cell immune surveillance disruption.Breast cancer research : BCR · 2025Trial
- Elacestrant in ER+, HER2- Metastatic Breast Cancer with ESR1-Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Landscape of Baseline and Acquired Genomic Alterations in Circulating Tumor DNA with Abemaciclib Alone or with Endocrine Therapy in Advanced Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative,Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Plasma ESR1 mutations and outcome to first-line paclitaxel and bevacizumab in patients with advanced ER-positive/HER2-negative breast cancer.Breast cancer research and treatment · 2023Trial
- Selective estrogen receptor degraders and their effect on the breast cancer immune microenvironment.The Journal of clinical investigation · 2026Review
- ESR1 mutations are associated with enhanced MTORC1 signaling in a context-dependent manner.Communications biology · 2026Article
- Identification and Validation of the ESR1 Y537S Mutant-Enriched Enhancer and Its Downstream Target IGFBP3.Cancer research communications · 2026Article
- CDKPredict: a clinicogenomic model for risk-adapted therapeutic intervention in breast cancer.Research square · 2026Article
- Actionable genetic landscape and dynamics in circulating DNA from 12,827 patients with metastatic breast cancer.Nature communications · 2026Article
- Beyond the canonical view: steroid receptor network plasticity and mechanosensitive chromatin integration in breast cancer.NAR cancer · 2026Review
- Discovery of ERα-Targeting Phytochemicals With In Vitro Cytotoxicity and Computational Prediction of Y537S Mutant Inhibition.Chemical biology & drug design · 2026Article
660 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 6 institutions in 1 country.
Funding
Abstract
Seventy percent of breast cancers express estrogen receptor (ER), and most of these are sensitive to ER inhibition. However, many such tumors for unknown reasons become refractory to inhibition of estrogen action in the metastatic setting. We conducted a comprehensive genetic analysis of two independent cohorts of metastatic ER-positive breast tumors and identified mutations in ESR1 affecting the ligand-binding domain (LBD) in 14 of 80 cases. These included highly recurrent mutations encoding p.Tyr537Ser, p.Tyr537Asn and p.Asp538Gly alterations. Molecular dynamics simulations suggest that the structures of the Tyr537Ser and Asp538Gly mutants involve hydrogen bonding of the mutant amino acids with Asp351, thus favoring the agonist conformation of the receptor. Consistent with this model, mutant receptors drive ER-dependent transcription and proliferation in the absence of hormone and reduce the efficacy of ER antagonists. These data implicate LBD-mutant forms of ER in mediating clinical resistance to hormonal therapy and suggest that more potent ER antagonists may be of substantial therapeutic benefit.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.