ESR1 Y537S

CI-VAR-00004818Explore in graph →NP_000116.2:p.Tyr537SerNM_000125.3:c.1610A>CClinVar 3257895 CIViC 50

Curated evidence

Evidence by cancer (9 items)

Grouped by cancer context first, then therapy. The same variant can be sensitizing in one cancer and irrelevant in another — contexts are never merged. 50 items per page; a cancer group may continue on the next page.

civicCuratedShowing 1–9 of 9 evidence items across 4 cancer contexts on this page · levels, directions and significance as curated at the source; each row links to its CIViC record.

Molecular profile	Therapy	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
Breast Carcinoma1
ESR1 Y537S	Selective Estrogen Receptor Covalent Antagonist H3B-6545	Predictive	B	Supports Sensitivity Response	4	submitted	EID12616 In a multicenter open label phase 1 to 2 trial in locally advanced or metastatic ER positive, HER2 negative breast carcinoma (NCT03250676; n = 151; RP2D cohort 450 mg once daily n = 115, response eval… (full text at CIViC) PMID 40830892 · Hamilton et al., 2025 · Open in CIViC	civic
Malignant Breast Neoplasm6
ESR1 D538G OR ESR1 Y537C OR ESR1 Y537N OR ESR1 Y537S OR ESR1 E380Q OR ESR1 Mutation	Lasofoxifene	Predictive	A	Supports Sensitivity Response	4	submitted	EID12934 In the randomized, open-label Phase II ELAINE-1 trial (n = 103), patients with ESR1‑mutated ER⁺/HER2⁻ mBC progressing after aromatase inhibitor plus CDK4/6 inhibitor therapy received either lasofoxife…

ClinVar

Clinical significance (0)

ClinVar interpretations are shown as structured records — significance, review status, star rating, conditions — never flattened into one word.

Data not yet available

No ClinVar interpretation attached to this variant.

Estrogen Receptor-positive Breast Cancer1unmapped disease
ESR1 Y537S	Elacestrant	Predictive	A	Supports Sensitivity Response	2	submitted	EID12220 In the randomized, open-label, phase 3 EMERALD trial (NCT03778931), the selective ER-degrader (SERD) elacestrant was assessed in ER+/HER2- breast cancer patients who had previously been treated with e… (full text at CIViC) PMID 35584336 · Bidard et al., 2022 · Open in CIViC	civic

Unmapped disease1unmapped disease
ESR1 Y537S	(functional)	Functional	D	Supports Gain Of Function	3	submitted	EID10019 MCF7 and SKBR3 cells were transfected with WT and mutant (Y537S, S463P/D538G, and D538G) ESR1. Their activity in the absence of ligand was measured with a luciferase assay. The mutants showed increase… (full text at CIViC) PMID 24185512 · Toy et al., 2013 · Open in CIViC	civic