ESR1 — gene · CancerIndex

Curated evidence

Clinical evidence (48)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 1–48 of 48 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
ESR1 D538G6
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	submitted	EID10018 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
Elacestrant	Estrogen Receptor-positive Breast CancerUNRESOLVED	Predictive	A	Supports Sensitivity Response	3	submitted	EID12219 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 ·

Cohorts

Alteration frequency by cohort (90)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved90 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Metastatic Breast Cancer (DFCI, Cancer Discov 2020) brca_dfci_2020	Invasive Breast Carcinoma	Ssm

Literature

Linked publications (6)

25 per page, newest first.

pubmedPublishedShowing 1–6 of 6 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial.
· J Clin Oncol · 2022 · PMID 35584336 · validated civic_curation pubmed
The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.
· Lancet Oncol · 2015 · PMID 25524798 · validated civic_curation pubmed
The Genetic Landscape and Clonal Evolution of Breast Cancer Resistance to Palbociclib plus Fulvestrant in the PALOMA-3 Trial.
· Cancer Discov · 2018 · PMID 30206110 · validated civic_curation pubmed
Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole.

ESR1 Expression2
Everolimus/Exemestane Regimen	Estrogen Receptor-positive Breast CancerUNRESOLVED	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID12907 In the same open-label randomized phase II BOLERO-6 trial (NCT01783444; n = 309), everolimus plus exemestane (n = 104) did not support improved PFS versus capecitabine monotherapy (n = 102) in ER+/HER… (full text at CIViC) PMID 29862411 · Jerusalem et al., 2018 · Open in CIViC	civic
〃	Estrogen Receptor-positive Breast CancerUNRESOLVED	Predictive	B	Supports Sensitivity Response	3	submitted	EID12908 In the open-label randomized phase II BOLERO-6 trial (NCT01783444; n = 309) of postmenopausal women with ER+/HER2− advanced breast cancer progressing on nonsteroidal aromatase inhibitors, everolimus p… (full text at CIViC) PMID 29862411 · Jerusalem et al., 2018 · Open in CIViC	civic

ESR1 Mutation3
Elacestrant	Malignant Breast Neoplasm	Predictive	A	Supports Sensitivity Response	4	accepted	EID11443 In a phase 3 trial (NCT03778931), the selective ER-degrader elacestrant was shown to increase progression free survival (PFS) in both ESR1 mutant and ESR1 wild type, ER-positive, HER2-negative breast … (full text at CIViC) PMID 35584336 · Bidard et al., 2022 · Open in CIViC	civic
Abemaciclib Regimen + Imlunestrant RegimenCombination	Breast Carcinoma	Predictive	A	Supports Sensitivity Response	4	submitted	EID12599 In the concurrently randomized cohort of the same phase 3 trial in ER-positive, HER2-negative breast carcinoma (NCT04975308; n = 426, 213 per arm), imlunestrant plus abemaciclib improved investigator-… (full text at CIViC) PMID 39660834 · Jhaveri et al., 2025 · Open in CIViC	civic
Aromatase Inhibitor + Fulvestrant + Imlunestrant RegimenSubstitutes	Breast Carcinoma	Predictive	A	Supports Sensitivity Response	4	submitted	EID12600 In a randomized, open-label phase 3 trial in ER-positive, HER2-negative breast carcinoma (EMBER-3, NCT04975308; n = 874; ESR1-mut subgroup n = 256), imlunestrant monotherapy (n=331) improved investiga… (full text at CIViC) PMID 39660834 · Jhaveri et al., 2025 · Open in CIViC	civic

ESR1 S463P3
Aromatase Inhibitor	Estrogen Receptor-positive Breast CancerUNRESOLVED	Predictive	D	Supports Resistance	2	accepted	EID1727 ESR1 S463P variants were observed after extensive treatment with hormonal therapy (aromatase inhibition). Expression of the S463P mutant was found to induce modest activity in the absence of hormone. … (full text at CIViC) PMID 24185512 · Toy et al., 2013 · Open in CIViC	civic
Elacestrant	Estrogen Receptor-positive Breast CancerUNRESOLVED	Predictive	A	Supports Sensitivity Response	2	submitted	EID12230 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
Palbociclib	Malignant Breast Neoplasm	Predictive	C	Supports Sensitivity Response	—	submitted	EID4815 In a phase 3 clinical trial (NCT01942135) of 360 premenopausal and postmenopausal women with advanced, hormone receptor-positive breast cancer who had progressed during prior endocrine therapy, patien… (full text at CIViC) PMID 27269946 · Fribbens et al., 2016 · Open in CIViC	civic