ESR1 ligand-binding-domain mutations confer aromatase-inhibitor (AI) resistance through c...
Deterministic view of the source YAML entity. Clinical authority remains with the cited source IDs and reviewer sign-off state.
| ID | BMA-ESR1-MUT-BREAST |
|---|---|
| Type | Actionability |
| Status | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Diseases | DIS-BREAST |
| Sources | SRC-CIVIC SRC-ESMO-BREAST-METASTATIC-2024 SRC-NCCN-BREAST-2025 |
Actionability Facts
| Biomarker | BIO-ESR1 |
|---|---|
| Variant | ligand-binding-domain hotspots — D538G, Y537S/N/C, L536H, E380Q; acquired during aromatase-inhibitor exposure in ~30-40% of HR+/HER2- metastatic breast progressing on AI |
| Disease | DIS-BREAST |
| ESCAT tier | IB |
| Recommended combinations | elacestrant monotherapy (ESR1-mut HR+/HER2- post-AI ± CDK4/6i per SRC-NCCN-BREAST-2025, SRC-ESMO-BREAST-METASTATIC-2024) |
| Contraindicated monotherapy | continuation of AI monotherapy at progression in confirmed ESR1-mutated disease (well-documented resistance per SRC-NCCN-BREAST-2025) |
| Evidence summary | ESR1 ligand-binding-domain mutations confer aromatase-inhibitor (AI) resistance through constitutive ER-α activation and are FDA-actionable in HR+/HER2-negative metastatic breast cancer post-AI ± CDK4/6i. Elacestrant (oral SERD) FDA-approved 2L+ for ESR1-mutated HR+/HER2- metastatic disease based on EMERALD (Bidard JCO 2022 — ESR1-mut subgroup mPFS 3.8 vs 1.9 mo, HR 0.55; benefit confined to ESR1-mut population) per SRC-NCCN-BREAST-2025, SRC-ESMO-BREAST-METASTATIC-2024. Detection by serial plasma ctDNA at progression is preferred per SRC-NCCN-BREAST-2025. |
Notes
ESCAT IB / OncoKB Level 1. ESR1 mutations are acquired (rarely present in primary tumor) and frequently polyclonal — ctDNA preferred over single-site biopsy. Other oral SERDs (camizestrant, giredestrant, imlunestrant) and combinations (elacestrant + abemaciclib, etc.) in late-stage development; not yet FDA-approved as of 2026-04 per SRC-NCCN-BREAST-2025. Source-gap: SRC-EMERALD-BIDARD-2022 not yet ingested.
Used By
No reverse references found in the YAML corpus.