ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Emergence of constitutively active estrogen receptor-α mutations in pretreated advanced estrogen receptor-positive breast cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05814224 (Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA), which is not on this map. Cited by 400 papers, 2 of them syntheses that pooled it.
What it found
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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.
Monitoring luminAl Breast Cancer Through the Evaluation of Mutational and epiGeNEtic alteraTIons of Circulating ESR1 DNA
Who cites it
400 citing papers in PubMed, 2 syntheses or guidelines pooled it, 651 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
- Hormone, Targeted, and Combinational Therapies for Breast Cancers: From Humans to Dogs.International journal of molecular sciences · 2024Pooled it
- 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
- 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
- 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
- Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- AMEERA-1 phase 1/2 study of amcenestrant, SAR439859, in postmenopausal women with ER-positive/HER2-negative advanced breast cancer.Nature communications · 2022Trial
- Biomarkers of Response and Resistance to Palbociclib Plus Letrozole in Patients With ERClinical cancer research : an official journal of the American Association for Cancer Research · 2022Trial
- Mutation analysis using cell-free DNA for endocrine therapy in patients with HR+ metastatic breast cancer.Scientific reports · 2021Trial
- Selective estrogen receptor degraders and their effect on the breast cancer immune microenvironment.The Journal of clinical investigation · 2026Review
- AGO Breast Panel Recommendations for the use of treatment-relevant biomarkers in early and advanced breast cancer-2026 Update.Breast (Edinburgh, Scotland) · 2026Review
- Integrative pipeline to profile and target endocrine therapy-insensitive cell populations in ER+ breast cancer.bioRxiv : the preprint server for biology · 2026Article
- Real-world treatment patterns and clinical outcomes in patients with emerging estrogen receptor 1 (ESR1)-mutated ER+ metastatic breast cancer in the U.S., 2018-2024.Breast cancer research and treatment · 2026Observational
- Bridging Biomarker Testing to Biomarker-Driven Targeted Therapy: Real-World ESR1 Mutation Testing Patterns and Prevalence in ER+, HER2- Metastatic Breast Cancer.Molecular diagnosis & therapy · 2026Article
- Article
- ExtremeResearch square · 2026Article
- Navigating first- and second-line treatment options in hormone receptor-positive HER2-negative advanced breast cancer.The oncologist · 2026Review
340 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
31 authors at 4 institutions in 1 country.
Funding
Abstract
purposeWe undertook this study to determine the prevalence of estrogen receptor (ER) α (ESR1) mutations throughout the natural history of hormone-dependent breast cancer and to delineate the functional roles of the most commonly detected alterations. EXPERIMENTAL
designWe studied a total of 249 tumor specimens from 208 patients. The specimens include 134 ER-positive (ER(+)/HER2(-)) and, as controls, 115 ER-negative (ER(-)) tumors. The ER(+) samples consist of 58 primary breast cancers and 76 metastatic samples. All tumors were sequenced to high unique coverage using next-generation sequencing targeting the coding sequence of the estrogen receptor and an additional 182 cancer-related genes.
resultsRecurring somatic mutations in codons 537 and 538 within the ligand-binding domain of ER were detected in ER(+) metastatic disease. Overall, the frequency of these mutations was 12% [9/76; 95% confidence interval (CI), 6%-21%] in metastatic tumors and in a subgroup of patients who received an average of 7 lines of treatment the frequency was 20% (5/25; 95% CI, 7%-41%). These mutations were not detected in primary or treatment-naïve ER(+) cancer or in any stage of ER(-) disease. Functional studies in cell line models demonstrate that these mutations render estrogen receptor constitutive activity and confer partial resistance to currently available endocrine treatments.
conclusionsIn this study, we show evidence for the temporal selection of functional ESR1 mutations as potential drivers of endocrine resistance during the progression of ER(+) breast cancer.
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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.