As mutações do domínio ligante-ligante ESR1 conferem resistência ao inhibidor da aromatase (IA) através de c...
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| ID | BMA-ESR1-MUT-BREAST |
|---|---|
| Tipo | Relevância terapêutica |
| Estado | reviewed 2026-04-27 | pending_clinical_signoff | actionability review required |
| Doenças | DIS-BREAST |
| Fontes | SRC-CIVIC SRC-ESMO-BREAST-METASTATIC-2024 SRC-NCCN-BREAST-2025 |
Fatos de ação
| Biomarcador | BIO-ESR1 |
|---|---|
| Variante | 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 |
| Doença | DIS-BREAST |
| Nível ESCAT | IB |
| Combinações recomendadas | elacestrant monotherapy (ESR1-mut HR+/HER2- post-AI ± CDK4/6i per SRC-NCCN-BREAST-2025, SRC-ESMO-BREAST-METASTATIC-2024) |
| Contraindicated monotherapy | continuação da IA em monoterapia na progressão na doença mutada confirmada por ESR1 (resistência bem documentada por SRC-NCCN-BREAST-2025) |
| Resumo das provas | 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. |
Notas
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.
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