ArticleCancer research2013
D538G mutation in estrogen receptor-α: A novel mechanism for acquired endocrine resistance in breast cancer.
Article in Cancer research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 233 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
233 citing papers in PubMed, 2 syntheses or guidelines pooled it, 400 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
- A Phase II Trial of Neoadjuvant MK-2206, an AKT Inhibitor, with Anastrozole in Clinical Stage II or IIIClinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Heterogeneity and clinical significance of ESR1 mutations in ER-positive metastatic breast cancer patients receiving fulvestrant.Nature communications · 2016Trial
- Identification and Validation of the ESR1 Y537S Mutant-Enriched Enhancer and Its Downstream Target IGFBP3.Cancer research communications · 2026Article
- Discovery of ERα-Targeting Phytochemicals With In Vitro Cytotoxicity and Computational Prediction of Y537S Mutant Inhibition.Chemical biology & drug design · 2026Article
- ExtremeResearch square · 2026Article
- Article
- The role of the SLC25A15 transporter in the formation of liver metastasis in ESR1-mutated breast cancer.Oncogene · 2026Article
- Review
- ESR1 fusions in breast cancer: functions, mechanisms and therapeutic opportunities.Translational breast cancer research : a journal focusing on translational research in breast cancer · 2026Review
- Pharmacologic targeting of midasin (MDN1) reveals a potential therapeutic vulnerability in ESR1-mutant breast cancer.Frontiers in pharmacology · 2026Article
- Activated glucocorticoid receptor is an estrogen receptor silencer in ER+ metastatic breast cancer.EMBO molecular medicine · 2026Article
- Targeting estrogen receptor alpha in breast cancer for novel therapies resistance mechanisms and future directions.Discover oncology · 2025Review
- Androgen Receptors Promote Oxidative Phosphorylation and Resistance to Palmitate Lipotoxicity in ER-Mutant Breast Cancer.Endocrinology · 2025Article
- DTC-Flow: a flow cytometry-based detection platform for characterizing bone marrow disseminated tumor cells in breast cancer.NPJ breast cancer · 2025Article
- Discovery of a novel small molecule degrader of wild type and mutant estrogen receptors using DNA encoded libraries.NPJ breast cancer · 2025Article
- TRIM24 as a therapeutic target in endocrine treatment-resistant breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- AND-1 is a critical regulator of R-loop dynamics and a target to overcome endocrine resistance.Science advances · 2025Article
173 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to endocrine therapy occurs in virtually all patients with estrogen receptor α (ERα)-positive metastatic breast cancer, and is attributed to various mechanisms including loss of ERα expression, altered activity of coregulators, and cross-talk between the ERα and growth factor signaling pathways. To our knowledge, acquired mutations of the ERα have not been described as mediating endocrine resistance. Samples of 13 patients with metastatic breast cancer were analyzed for mutations in cancer-related genes. In five patients who developed resistance to hormonal therapy, a mutation of A to G at position 1,613 of ERα, resulting in a substitution of aspartic acid at position 538 to glycine (D538G), was identified in liver metastases. Importantly, the mutation was not detected in the primary tumors obtained prior to endocrine treatment. Structural modeling indicated that D538G substitution leads to a conformational change in the ligand-binding domain, which mimics the conformation of activated ligand-bound receptor and alters binding of tamoxifen. Indeed, experiments in breast cancer cells indicated constitutive, ligand-independent transcriptional activity of the D538G receptor, and overexpression of it enhanced proliferation and conferred resistance to tamoxifen. These data indicate a novel mechanism of acquired endocrine resistance in breast cancer. Further studies are needed to assess the frequency of D538G-ERα among patients with breast cancer and explore ways to inhibit its activity and restore endocrine sensitivity.
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.