# ESR1 mutation

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

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-07
- Also known as: 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

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Estrogen_receptor_alpha
- Wikipedia: https://en.wikipedia.org/wiki/Estrogen_receptor_alpha

## Connected records

- cancers: [HR-positive / HER2-negative breast cancer](https://onco.cc/cancers/breast-hr-positive/)
- technologies: [FES PET (oestrogen receptor imaging)](https://onco.cc/technologies/fes-pet/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- targets: [Estrogen receptor (ERα)](https://onco.cc/targets/estrogen-receptor/)
- 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/), [Vepdegestrant](https://onco.cc/drugs/vepdegestrant/)
- trials: [EMBER-3](https://onco.cc/trials/ember-3/), [EMERALD](https://onco.cc/trials/emerald/), [SERENA-6](https://onco.cc/trials/serena-6/)
- pairings: [Oral SERD + CDK4/6 inhibitor after ESR1 emergence](https://onco.cc/pairings/oral-serd-plus-cdk46-after-esr1/)
- ideas: [Molecular-progression switching beyond ESR1](https://onco.cc/ideas/idea-ctdna-switch-generalised/)
- terms: [Receptor conversion: when the receptors change between the primary and a recurrence](https://onco.cc/terms/receptor-conversion-breast/)
- bottlenecks: [Acquired resistance to every therapy](https://onco.cc/bottlenecks/b-resistance/), [Tumour heterogeneity and clonal evolution](https://onco.cc/bottlenecks/b-tumor-heterogeneity/)
- pathways: [Resistance routes: how a blocked pathway comes back](https://onco.cc/pathways/resistance-routes-map/), [Transcriptional machinery & addiction](https://onco.cc/pathways/transcription-addiction/)
- biomarkers: [ESR1 mutation (ligand-binding domain, usually in ctDNA)](https://onco.cc/biomarkers/esr1-mutation-ctdna/)

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