ESR1 mutation (ligand-binding domain)

Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.

ID	`BIO-ESR1`
Type	Biomarker
Aliases	ER-α mutationESR1 D538GESR1 LBDESR1 LBD mutationESR1 Y537SМутація ESR1 (ліганд-зв'язуючий домен)
Status	reviewed 2026-04-27 \| pending_clinical_signoff
Diseases	None declared
Sources	`SRC-ESMO-BREAST-METASTATIC-2024` `SRC-NCCN-BREAST-2025` `SRC-ONCOKB`

Biomarker Facts

Biomarker type	gene_mutation
Mutation details	{"functional_impact": "Constitutive ER-α activation in absence of estrogen — drives aromatase-inhibitor resistance", "gene": "ESR1", "gene_hugo_id": "HGNC:3467", "hotspots": ["D538G", "Y537S", "Y537N", "Y537C", "L536H", "E380Q"], "variant_type": "missense (ligand-binding domain)"}
Measurement	MethodPlasma ctDNA NGS (preferred — high concordance + serial monitoring) OR tumor-tissue NGS Unitscategorical (positive/negative); VAF reported Sensitivity requirementctDNA assay LoD ~0.5% VAF (Guardant360 / FoundationOne Liquid CDx); polyclonal ESR1 mutations common
Related biomarkers	`BIO-ESTROGEN-RECEPTOR` `BIO-PIK3CA-MUTATION`

Notes

Acquired in ~30–40% of HR+ HER2− metastatic breast progressing on aromatase inhibitor; <1% in primary tumors at diagnosis. Predictive for elacestrant (oral SERD; EMERALD trial — PFS benefit limited to ESR1-mut subgroup). Test on ctDNA at progression on AI ± CDK4/6i. Other oral SERDs (camizestrant, giredestrant, imlunestrant) and PROTACs in late development. Y537S confers more aggressive biology than D538G in some series. ctDNA is the preferred specimen because ESR1 mutations are typically subclonal in tissue and frequently polyclonal across metastatic sites.

Used By

Actionability

BMA-ESR1-MUT-BREAST - ESR1 ligand-binding-domain mutations confer aromatase-inhibitor (AI) resistance through c...

Indications

IND-BREAST-HR-POS-2L-ESR1-ELACESTRANT - IND-BREAST-HR-POS-2L-ESR1-ELACESTRANT

Questionnaires

QUEST-BREAST-1L-STUB - Invasive breast cancer — first line