{"entity":{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","aka":["ESR1","ESR1 mutations","ESR1-mutant","ESR1-mutated","ESR1m","ESR1 mutation on ctDNA","ESR1 ctDNA testing","oestrogen receptor gene mutation","estrogen receptor gene mutation","Y537S","D538G","ESR1 ligand-binding domain mutation"],"tldr":"A change in the oestrogen receptor gene that lets the cancer grow without oestrogen, so aromatase inhibitors stop working. Found in the blood in about a third of patients after hormone therapy.","summary":"Ligand-binding-domain mutations (Y537S, D538G, E380Q and others) arise under aromatase-inhibitor pressure in 30-40% of endocrine-resistant tumours and are rare at diagnosis (<5%). Detected by ctDNA (Guardant360 CDx is the companion diagnostic). Predicts resistance to AIs but retained sensitivity to SERDs, oral SERDs, and PROTAC degraders; the basis for elacestrant, imlunestrant, vepdegestrant, and camizestrant labels.","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Estrogen_receptor_alpha","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Estrogen_receptor_alpha"}],"tags":[],"related":[],"cancers":["breast-hr-positive"],"sections":[],"technologies":["liquid-biopsy"],"targets":["estrogen-receptor"],"drugs":["elacestrant","imlunestrant","vepdegestrant","camizestrant"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/esr1-mutation/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"}],"technology":[{"id":"fes-pet","kind":"technology","name":"FES PET (oestrogen receptor imaging)","route":"/technologies/fes-pet/"},{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"target":[{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}],"drug":[{"id":"camizestrant","kind":"drug","name":"Camizestrant","route":"/drugs/camizestrant/"},{"id":"elacestrant","kind":"drug","name":"Elacestrant","route":"/drugs/elacestrant/"},{"id":"guardant360-cdx","kind":"drug","name":"Guardant360 CDx","route":"/drugs/guardant360-cdx/"},{"id":"imlunestrant","kind":"drug","name":"Imlunestrant","route":"/drugs/imlunestrant/"},{"id":"vepdegestrant","kind":"drug","name":"Vepdegestrant","route":"/drugs/vepdegestrant/"}],"trial":[{"id":"ember-3","kind":"trial","name":"EMBER-3","route":"/trials/ember-3/"},{"id":"emerald","kind":"trial","name":"EMERALD","route":"/trials/emerald/"},{"id":"serena-6","kind":"trial","name":"SERENA-6","route":"/trials/serena-6/"}],"pairing":[{"id":"oral-serd-plus-cdk46-after-esr1","kind":"pairing","name":"Oral SERD + CDK4/6 inhibitor after ESR1 emergence","route":"/pairings/oral-serd-plus-cdk46-after-esr1/"}],"idea":[{"id":"idea-ctdna-switch-generalised","kind":"idea","name":"Molecular-progression switching beyond ESR1","route":"/ideas/idea-ctdna-switch-generalised/"}],"term":[{"id":"receptor-conversion-breast","kind":"term","name":"Receptor conversion: when the receptors change between the primary and a recurrence","route":"/terms/receptor-conversion-breast/"}],"bottleneck":[{"id":"b-resistance","kind":"bottleneck","name":"Acquired resistance to every therapy","route":"/bottlenecks/b-resistance/"},{"id":"b-tumor-heterogeneity","kind":"bottleneck","name":"Tumour heterogeneity and clonal evolution","route":"/bottlenecks/b-tumor-heterogeneity/"}],"pathway":[{"id":"resistance-routes-map","kind":"pathway","name":"Resistance routes: how a blocked pathway comes back","route":"/pathways/resistance-routes-map/"},{"id":"transcription-addiction","kind":"pathway","name":"Transcriptional machinery & addiction","route":"/pathways/transcription-addiction/"}],"biomarker":[{"id":"esr1-mutation-ctdna","kind":"biomarker","name":"ESR1 mutation (ligand-binding domain, usually in ctDNA)","route":"/biomarkers/esr1-mutation-ctdna/"}]}}