# ESR1 mutation (ligand-binding domain, usually in ctDNA)

Source: https://onco.cc/biomarkers/esr1-mutation-ctdna/  
OnCo record `esr1-mutation-ctdna` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: ESR1 mutation; ESR1-mutated; ESR1 Y537S; ESR1 D538G; ESR1m; ESR1 mutant breast cancer; acquired ESR1 mutation
- Tags: biomarker; hormone-receptor; resistance

## Sources

- ORSERDU prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=aa66ae5c-2bd2-4444-8178-b55651e054ef
- Inluriyo prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5bc172e4-e8a2-441a-be52-279a7f890196

## Connected records

- biomarkers: [ctDNA MRD positivity (molecular residual disease after curative treatment)](https://onco.cc/biomarkers/ctdna-mrd-positive/), [ER status (oestrogen receptor by IHC)](https://onco.cc/biomarkers/er-status/), [PIK3CA mutation](https://onco.cc/biomarkers/pik3ca-hotspot-mutation/)
- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/), [HR-positive metastatic breast cancer after CDK4/6 inhibitors](https://onco.cc/cancers/hr-positive-metastatic-post-cdk46/)
- drugs: [Camizestrant](https://onco.cc/drugs/camizestrant/), [Elacestrant](https://onco.cc/drugs/elacestrant/), [Guardant360 CDx](https://onco.cc/drugs/guardant360-cdx/), [Imlunestrant](https://onco.cc/drugs/imlunestrant/)
- terms: [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [ESR1 mutation](https://onco.cc/terms/esr1-mutation/), [Selective oestrogen receptor degrader (SERD)](https://onco.cc/terms/serd/)
- targets: [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/)

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