ArticleCancer discovery2024
ESR1 F404 Mutations and Acquired Resistance to Fulvestrant in ESR1-Mutant Breast Cancer.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03182634 (A Multiple Parallel Cohort, Multi-centre Phase IIa Trial Aiming to Provide Proof of Principle Efficacy for Designated Targeted Therapies in Patients With Advanced Breast Cancer Where the Targetable Mutation is Identified Through ctDNA), which is not on this map. Cited by 32 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 Multiple Parallel Cohort, Multi-centre Phase IIa Trial Aiming to Provide Proof of Principle Efficacy for Designated Targeted Therapies in Patients With Advanced Breast Cancer Where the Targetable Mutation is Identified Through ctDNA
Who cites it
32 citing papers in PubMed, 2 syntheses or guidelines pooled it, 31 citations in OpenAlex.
- Circulating tumour DNA and its clinical relevance in predicting progression-free survival and overall survival in patients with advanced breast cancer: a systematic review and meta-analysis.Breast cancer research and treatment · 2026Pooled it
- 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
- HDAC inhibitor tucidinostat and metronomic capecitabine plus endocrine therapy for patients with HR-positive HER2-negative advanced breast cancer after CDK4/6 inhibitors treatment: clinical findings and exploratory circulating tumor cell and ctDNA biomarker analyses of a multicenter, phase 2 study (SYSUCC-020 trial).Signal transduction and targeted therapy · 2026Trial
- Selective estrogen receptor degraders and their effect on the breast cancer immune microenvironment.The Journal of clinical investigation · 2026Review
- Cracking ERα Y537S Resistance: Explainable Machine Learning-Guided Discovery and Molecular Dynamics Validation of Stable Candidate Ligands.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Hydrophobic Tag Degraders Overcome Endocrine-Resistant Breast Cancer by Recruiting HSP27-Mediated E3 Ligase Complex for ERα Proteasomal Degradation.Angewandte Chemie (International ed. in English) · 2026Article
- A PML1-CCL5-PI3K/MAPK feedback loop governs survival of endocrine-resistant breast cancer cells.Cell death and differentiation · 2026Review
- Targeting a super-enhancer induced aldehyde dehydrogenase metabolic loop mitigates CDK4/6 inhibitor resistance in estrogen receptor-positive cancers.Nature communications · 2026Article
- The natural L370F ERα variant confers endocrine resistance and sensitivity to ATRA in metastatic breast cancer cells.Cell communication and signaling : CCS · 2026Article
- 4-Methylcatechol attenuates diabetic myocardial disorder via the ESR1-PI3K-AKT pathway.Frontiers in pharmacology · 2026Article
- Concurrent genomic assessment of circulating tumour cells and ctDNA to guide therapy in metastatic breast cancer.BMC cancer · 2025Article
- Integrated network toxicology and molecular simulations uncover the molecular mechanism and core targets of DNBaP-induced lung cancer.Discover oncology · 2025Article
- Safety evaluation of selective estrogen receptor degraders (SERDs) using real-world evidence from the FDA Adverse Event Reporting System (FAERS).Scientific reports · 2025Article
- The promise of ctDNA-based, molecularly-driven early switch therapy from PADA-1 to SERENA-6.Breast cancer research and treatment · 2025Review
- Evolutionary Overview and Future Perspectives: ESR1 Mutations, Liquid Biopsy, and Artificial Intelligence for a New Era of Personalized Medicine in ER+ Breast Cancer.Molecular diagnosis & therapy · 2025Review
- Cold atmospheric plasma restores fulvestrant sensitivity by inhibiting CCND3 in the drug-resistant breast cancer cells.Scientific reports · 2025Article
- Diagnostic utility of ESR1 mutation detection in liquid biopsy of metastatic breast cancer patients.Virchows Archiv : an international journal of pathology · 2025Article
- Benzestrol Isomer Stereochemistry Determines the Distinct Estrogenic Activities and Conformations of the Eight Isomers When Bound to Estrogen Receptor α.ACS pharmacology & translational science · 2025Article
- Genomic Predictive Biomarkers in Breast Cancer: TheInternational journal of molecular sciences · 2025Review
- Targeting CDK2 and other novel cell cycle targets for breast cancer therapy.Expert opinion on therapeutic targets · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 6 institutions in 2 countries.
Funding
Abstract
Fulvestrant is used to treat patients with hormone receptor-positive advanced breast cancer, but acquired resistance is poorly understood. PlasmaMATCH Cohort A (NCT03182634) investigated the activity of fulvestrant in patients with activating ESR1 mutations in circulating tumor DNA (ctDNA). Baseline ESR1 mutations Y537S are associated with poor outcomes and Y537C with good outcomes. Sequencing of baseline and EOT ctDNA samples (n = 69) revealed 3/69 (4%) patients acquired novel ESR1 F404 mutations (F404L, F404I, and F404V), in cis with activating mutations. In silico modeling revealed that ESR1 F404 contributes to fulvestrant binding to estrogen receptor-alpha (ERα) through a pi-stacking bond, with mutations disrupting this bond. In vitro analysis demonstrated that single F404L, E380Q, and D538G models were less sensitive to fulvestrant, whereas compound mutations D538G + F404L and E380Q + F404L were resistant. Several oral ERα degraders were active against compound mutant models. We have identified a resistance mechanism specific to fulvestrant that can be targeted by treatments in clinical development. SIGNIFICANCE: Novel F404 ESR1 mutations may be acquired to cause overt resistance to fulvestrant when combined with preexisting activating ESR1 mutations. Novel combinations of mutations in the ER ligand binding domain may cause drug-specific resistance, emphasizing the potential of similar drug-specific mutations to impact the efficacy of oral ER degraders in development. This article is featured in Selected Articles from This Issue, p. 201.
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.