Biomarker · Gene alteration

ESR1 mutation

Acquired mutations in the ESR1 ligand-binding domain detected in tumor tissue or circulating tumor DNA; used as a predictive marker in ER-positive breast cancer after endocrine therapy.

CI-BIO-00000005ESR1 graph →NCIt C136629

Also calledESR1-mutated · ESR1 ligand-binding domain mutation · D538G · Y537S

Derived

Associated cancers (1)

Cancers mapped in ACCEPTED CIViC predictive, prognostic or diagnostic items whose variant (molecular markers) or gene (gene-level markers) is in this biomarker's scope. Counts by type and native level; each row links to the cancer's evidence tab.

Computedrule biomarker-links-v1

Cancer	Items	Predictive	Prognostic	Diagnostic	Levels A / B / C / D / E
Malignant Breast Neoplasm	7	7	—	—	1 / 1 / 1 / 4 / 0

Derived

Drugs with predictive evidence (6)

Therapies named in in-scope PREDICTIVE CIViC items, plus targets of PREDICTS_RESPONSE_TO knowledge edges from in-scope variants. Sensitivity and resistance are counted separately and never merged into a verdict.

Computedrule biomarker-links-v1

Drug	CIViC items	Sensitivity	Resistance	Best level	Edges (S / R)	Cancer context
FulvestrantSmall Molecule	3	2	1	B	2 / 1	Malignant Breast Neoplasm
Hormone Therapy	2	—	2	D	0 / 2	Malignant Breast Neoplasm
TamoxifenSmall Molecule

Curated evidence

Predictive evidence items (7)

ACCEPTED CIViC predictive items in scope, grouped by molecular profile and therapy with native level, direction and cancer context. 50 per page.

civicCuratedShowing 1–7 of 7 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 Mutation1
Elacestrant

Regulatory

Approvals mentioning the linked drugs (162)

Approval records of the derived drug set, plus records whose indication text names this biomarker. Each record names its authority, jurisdiction, indication text and status — a drug approved in one jurisdiction for one indication is not 'approved' in general, and an approval listed here is not necessarily restricted to this biomarker.

Computedrule biomarker-links-v1

ema

Clinical trials

Active trials (170)

Trials with an active ClinicalTrials.gov status, an intervention mapped to a derived drug and a condition mapped to an associated cancer. 84 recruiting · 46 active phase 3 · 669 in any status. Most recently updated first, 50 per page.

Computedrule biomarker-links-v1

clinicaltrialsPublishedShowing 1–50 of 170 active studies · status and phase as posted by the registrant; each row links to the study record.

NCT	Title	Status	Phase	Enrollment (n)	Sponsor	Countries	Last update	Source
NCT05646862	A Study Evaluating the Efficacy and Safety of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus Fulvestrant in Participants With HR-Positive, HER2-Negative, PIK3CA Mutated, Locally Advanced or Metastatic Breast Cancer Post CDK4/6i and Endocrine Combination Therapy

Literature

Linked publications (5)

Publications linked to the scope variant(s) through PubMed entity edges; 25 per page, newest first.

pubmedPublishedShowing 1–5 of 5 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 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.
· Oncotarget · 2017 · PMID 28978004 · validated civic_curation pubmed
Activating ESR1 mutations in hormone-resistant metastatic breast cancer.

ESR1 D538G3
Hormone Therapy	Malignant Breast Neoplasm	Predictive	D	Supports Resistance	3	accepted	EID243 MCF7 cell lines harboring the D538G mutation in the ligand-binding domain of ESR1 have shown resistance to hormone therapy. PMID 24185512 · Toy et al., 2013 · Open in CIViC	civic
Letrozole + PalbociclibCombination	Malignant Breast Neoplasm	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID4814 In a study of 16 patients with metastatic breast cancer (NCT02142868) treated with palbociclib in combination with letrozole, patients with ESR1 mutations (5/16), including ESR1 D538G (n=2), detected … (full text at CIViC) PMID 28978004 · Gyanchandani et al., 2017 · Open in CIViC	civic
Fulvestrant + TamoxifenSubstitutes	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	5	accepted	EID291 Using an estrogen response element (ERE)-luciferase reporter system co-transfected with one of five ESR1 mutants, the N538G ligand binding domain mutation was shown to result in constitutive activity … (full text at CIViC) PMID 24185510 · Robinson et al., 2013 · Open in CIViC	civic

ESR1 Y537S2
Hormone Therapy	Malignant Breast Neoplasm	Predictive	D	Supports Resistance	3	accepted	EID246 MCF7 cell lines harboring the L537S mutation in the ligand-binding domain of ESR1 have shown resistance to hormone therapy. PMID 24185512 · Toy et al., 2013 · Open in CIViC	civic
Fulvestrant + TamoxifenSubstitutes	Malignant Breast Neoplasm	Predictive	D	Supports Sensitivity Response	5	accepted	EID294 Using an estrogen response element (ERE)-luciferase reporter system co-transfected with one of five ESR1 mutants, the Y537S ligand binding domain mutation was shown to result in constitutive activity … (full text at CIViC) PMID 24185510 · Robinson et al., 2013 · Open in CIViC	civic

Drug	Jurisdiction · authority	Cancer	Indication	Status	Approval date	Source
Elacestrant	EU EMA	Malignant Breast Neoplasm	Orserdu monotherapy is indicated for the treatment of postmenopausal women, and men, with estrogen receptor (ER) positive, HER2-negative, locally advanced or metastatic breast cancer with an activating ESR1 mutation who have disease progression following at least one line of endocrine therapy including a CDK 4/6 inhibitor.	approved	Sep 15, 2023	ema
Fulvestrant	EU EMA	Malignant Breast Neoplasm	Fulvestrant is indicated for the treatment of estrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women: not previously treated with endocrine therapy, or with disease relapse on or after adjuvant anti-estrogen therapy, or disease progression on antiestrogen therapy.	approved	Jan 8, 2018	ema
Fulvestrant	EU EMA	Malignant Breast Neoplasm	Faslodex is indicated as monotherapy for the treatment of estrogen receptor positive, locally advanced or metastatic breast cancer in postmenopausal women: not previously treated with endocrine therapy, or with disease relapse on or after adjuvant antiestrogen therapy, or disease progression on antiestrogen therapy. in combination with palbociclib for the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer in women who have received prior endocrine therapy. In pre- or perimenopausal women, the combination treatment with palbociclib should be combined with a luteinizing hormone releasing hormone (LHRH) agonist.	approved	Mar 9, 2004	ema
Palbociclib	EU EMA	Malignant Breast Neoplasm	Palbociclib Viatris is indicated for the treatment of hormone receptor (HR)‑positive, human epidermal growth factor receptor 2 (HER2)‑negative locally advanced or metastatic breast cancer. in combination with an aromatase inhibitor; in combination with fulvestrant in women who have received prior endocrine therapy (see section 5.1). In pre‑ or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone‑releasing hormone (LHRH) agonist.	approved	Jun 19, 2026	ema
Palbociclib	EU EMA	Malignant Breast Neoplasm	Ibrance is indicated for the treatment of hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative locally advanced or metastatic breast cancer: in combination with an aromatase inhibitor; in combination with fulvestrant in women who have received prior endocrine therapy. In pre- or perimenopausal women, the endocrine therapy should be combined with a luteinizing hormone releasing hormone (LHRH) agonist.	approved	Nov 9, 2016	ema