{"entity":{"id":"esr1-mutation-ctdna","kind":"biomarker","name":"ESR1 mutation (ligand-binding domain, usually in ctDNA)","aka":["ESR1 mutation","ESR1-mutated","ESR1 Y537S","ESR1 D538G","ESR1m","ESR1 mutant breast cancer","acquired ESR1 mutation"],"tldr":"ESR1 mutations arise in the oestrogen receptor's ligand-binding domain after aromatase inhibitor treatment, letting the receptor work without oestrogen. They are usually found in a blood test and select the oral SERDs elacestrant and imlunestrant.","summary":"Mutations between codons 310 and 547 (Y537S, Y537N, D538G, E380Q and others) are acquired under aromatase inhibitors in 30 to 40 percent of metastatic HR-positive breast cancers and are best detected in plasma cell-free DNA because they are subclonal and heterogeneous. Elacestrant (Orserdu, 2023) is labelled for ER-positive HER2-negative ESR1-mutated advanced breast cancer after at least one line of endocrine therapy, as detected by an FDA-authorised test; imlunestrant (Inluriyo, 2025) for the same population; vepdegestrant was added to the Guardant360 CDx claims in 2026. Guardant360 CDx is the listed companion diagnostic for all three. Guidelines recommend repeat plasma testing at each progression because the mutation appears over time.","asOf":"2026-09-23","links":[{"label":"ORSERDU prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa66ae5c-2bd2-4444-8178-b55651e054ef"},{"label":"Inluriyo prescribing information (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5bc172e4-e8a2-441a-be52-279a7f890196"}],"tags":["biomarker","hormone-receptor","resistance"],"related":["er-status","pik3ca-hotspot-mutation"],"cancers":["breast-hr-positive","hr-positive-metastatic-post-cdk46"],"sections":[],"technologies":[],"targets":[],"drugs":["elacestrant","imlunestrant","camizestrant","guardant360-cdx"],"companies":[],"institutions":[],"pathways":[],"terms":["esr1-mutation","ctdna","serd"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"target":"estrogen-receptor","measurement":"sequencing-variant","scoringRule":{"text":"An ESR1 missense mutation between codons 310 and 547 (or the listed hotspots E380, V422del, S463, L469, L536, Y537, D538) in plasma cell-free DNA or tumour tissue by sequencing.","quote":"ESR1 missense mutations between codons 310 and 547","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools","sourceLabel":"FDA: List of FDA-Authorized Companion Diagnostic Devices"},"thresholds":[{"value":"ESR1-mutated, after at least one line of endocrine therapy","drugId":"elacestrant","cancerId":"breast-hr-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa66ae5c-2bd2-4444-8178-b55651e054ef","quote":"ORSERDU is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)‑negative, ESR1 -mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy.","status":"current"},{"value":"ESR1-mutated, after at least one line of endocrine therapy","drugId":"imlunestrant","cancerId":"breast-hr-positive","regulator":"FDA","source":"https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5bc172e4-e8a2-441a-be52-279a7f890196","quote":"INLURIYO is indicated for the treatment of adults with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, estrogen receptor-1 ( ESR1 )-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy.","status":"current"}],"tests":["guardant360-cdx","foundationone-liquid-cdx","foundationone-cdx","tempus-xt"],"assays":["guardant360-cdx","foundationone-liquid-cdx"],"companionDiagnostics":[{"device":"Guardant360 CDx","maker":"Guardant Health","companyId":"guardant-health","drugs":["elacestrant"],"indication":"Breast Cancer - Plasma","pma":"P200010/S010 (01/27/2023)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"},{"device":"Guardant360 CDx","maker":"Guardant Health","companyId":"guardant-health","drugs":["imlunestrant"],"indication":"Breast Cancer - Plasma","pma":"P200010/S021 (09/25/2025)","source":"https://www.fda.gov/medical-devices/in-vitro-diagnostics/list-cleared-or-approved-companion-diagnostic-devices-in-vitro-and-imaging-tools"}],"forPatient":"If a blood test finds an ESR1 mutation after your cancer has progressed on an aromatase inhibitor, elacestrant or imlunestrant tablets are on label as the next hormone treatment. The mutation is usually not present at diagnosis, so the blood test is repeated each time the cancer grows; a negative result now does not rule out a positive one later."},"route":"/biomarkers/esr1-mutation-ctdna/","neighbours":{"biomarker":[{"id":"ctdna-mrd-positive","kind":"biomarker","name":"ctDNA MRD positivity (molecular residual disease after curative treatment)","route":"/biomarkers/ctdna-mrd-positive/"},{"id":"er-status","kind":"biomarker","name":"ER status (oestrogen receptor by IHC)","route":"/biomarkers/er-status/"},{"id":"pik3ca-hotspot-mutation","kind":"biomarker","name":"PIK3CA mutation","route":"/biomarkers/pik3ca-hotspot-mutation/"}],"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"hr-positive-metastatic-post-cdk46","kind":"cancer","name":"HR-positive metastatic breast cancer after CDK4/6 inhibitors","route":"/cancers/hr-positive-metastatic-post-cdk46/"}],"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/"}],"term":[{"id":"ctdna","kind":"term","name":"Circulating tumour DNA (ctDNA)","route":"/terms/ctdna/"},{"id":"esr1-mutation","kind":"term","name":"ESR1 mutation","route":"/terms/esr1-mutation/"},{"id":"serd","kind":"term","name":"Selective oestrogen receptor degrader (SERD)","route":"/terms/serd/"}],"target":[{"id":"estrogen-receptor","kind":"target","name":"Estrogen receptor (ERα)","route":"/targets/estrogen-receptor/"}]}}