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

openfda

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
Camizestrant	US FDA	Malignant Breast Neoplasm	in combination with a CDK4/6 inhibitor (abemaciclib, palbociclib, or ribociclib) for the treatment of adult patients with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative, locally advanced or metastatic breast cancer upon detection of ESR1 mutation during aromatase inhibitor and CDK4/6 inhibitor therapy, based on an FDA authorized test. ( 1 , 2.1 ) This indication is approved under accelerated approval based on progression-free survival as measured from detection of ESR1 mutation. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). ( 1 )accelerated	approved	Sep 4, 2026	openfda
Elacestrant	US FDA	Malignant Breast Neoplasm	ORSERDU is indicated for the treatment of postmenopausal women or adult men with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)‑negative, ESR1 -mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test [see Dosage and Administration ( 2.1 )] , with disease progression following at least one line of endocrine therapy. ORSERDU is an estrogen receptor antagonist indicated for: treatment of postmenopausal women or adult men, with ER-positive, HER2-negative, ESR1 -mutated advanced or metastatic breast cancer, as detected by an FDA-authorized test, with disease progression following at least one line of endocrine therapy ( 1 )	approved	Jan 27, 2023	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2021-05-12 (see label)	approved	May 12, 2021	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2020-07-28 (see label)	approved	Jul 28, 2020	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2020-05-13 (see label)	approved	May 13, 2020	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2019-11-21 (see label)	approved	Nov 21, 2019	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	Monotherapy CLIGAVYX is indicated for the treatment of: Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. Combination Therapy CLIGAVYX is indicated for the treatment of: HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. CLIGAVYX is an estrogen receptor antagonist indicated for the treatment of: Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy. ( 1 ) HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. ( 1 ) HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib, as initial endocrine based therapy or following disease progression on endocrine therapy. ( 1 ) HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. ( 1 )	approved	Aug 19, 2019	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	Fulvestrant Injection is an estrogen receptor antagonist indicated for the treatment of: Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy. ( 1 ) HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. ( 1 ) HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib, as initial endocrine based therapy or following disease progression on endocrine therapy. ( 1 ) HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. ( 1 ) Monotherapy Fulvestrant Injection is indicated for the treatment of: Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. Combination Therapy Fulvestrant Injection is indicated for the treatment of: HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy. HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy.	approved	May 20, 2019	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2019-03-11 (see label)	approved	Mar 11, 2019	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2018-07-05 (see label)	approved	Jul 5, 2018	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2017-11-14 (see label)	approved	Nov 14, 2017	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2017-08-25 (see label)	approved	Aug 25, 2017	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2016-03-02 (see label)	approved	Mar 2, 2016	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2012-11-09 (see label)	approved	Nov 9, 2012	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2011-05-17 (see label)	approved	May 17, 2011	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2010-09-09 (see label)	approved	Sep 9, 2010	openfda
Fulvestrant	US FDA	—	Efficacy supplement 2003-12-24 (see label)	approved	Dec 24, 2003	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. (1)	approved	Apr 25, 2002	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib, as initial endocrine based therapy or following disease progression on endocrine therapy. (1)	approved	Apr 25, 2002	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy, or	approved	Apr 25, 2002	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	HR-positive advanced breast cancer in postmenopausal women with disease progression following endocrine therapy. Combination Therapy FASLODEX is indicated for the treatment of:	approved	Apr 25, 2002	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	HR-positive, HER2-negative advanced or metastatic breast cancer in postmenopausal women in combination with ribociclib as initial endocrine based therapy or following disease progression on endocrine therapy.	approved	Apr 25, 2002	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. (1)	approved	Apr 25, 2002	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	HR-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib or abemaciclib in women with disease progression after endocrine therapy. FASLODEX is an estrogen receptor antagonist indicated for the treatment of:	approved	Apr 25, 2002	openfda
Fulvestrant	US FDA	Malignant Breast Neoplasm	Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer in postmenopausal women not previously treated with endocrine therapy. (1)	approved	Apr 25, 2002	openfda
Letrozole	US FDA	—	Efficacy supplement 2010-04-30 (see label)	approved	Apr 30, 2010	openfda
Letrozole	US FDA	—	Efficacy supplement 2010-03-02 (see label)	approved	Mar 2, 2010	openfda
Letrozole	US FDA	—	Efficacy supplement 2010-03-02 (see label)	approved	Mar 2, 2010	openfda
Letrozole	US FDA	—	Efficacy supplement 2005-12-28 (see label)	approved	Dec 28, 2005	openfda
Letrozole	US FDA	—	Efficacy supplement 2004-10-29 (see label)	approved	Oct 29, 2004	openfda
Letrozole	US FDA	—	Efficacy supplement 2003-02-26 (see label)	approved	Feb 26, 2003	openfda
Letrozole	US FDA	—	Efficacy supplement 2003-01-17 (see label)	approved	Jan 17, 2003	openfda
Letrozole	US FDA	—	Efficacy supplement 2001-01-10 (see label)	approved	Jan 10, 2001	openfda
Letrozole	US FDA	Malignant Breast Neoplasm	Extended adjuvant treatment of postmenopausal women with early breast cancer who have received prior standard adjuvant tamoxifen therapy.	approved	Jul 25, 1997	openfda
Letrozole	US FDA	Malignant Breast Neoplasm	First and second-line treatment of postmenopausal women with hormone receptor positive or unknown advanced breast cancer.	approved	Jul 25, 1997	openfda
Letrozole	US FDA	Malignant Breast Neoplasm	Adjuvant treatment of postmenopausal women with hormone receptor positive early breast cancer.	approved	Jul 25, 1997	openfda
Palbociclib	US FDA	—	Efficacy supplement 2026-06-24 (see label)	approved	Jun 24, 2026	openfda
Palbociclib	US FDA	—	Efficacy supplement 2026-06-24 (see label)	approved	Jun 24, 2026	openfda
Palbociclib	US FDA	—	Efficacy supplement 2025-09-16 (see label)	approved	Sep 16, 2025	openfda
Palbociclib	US FDA	—	Efficacy supplement 2025-09-16 (see label)	approved	Sep 16, 2025	openfda
Palbociclib	US FDA	—	Efficacy supplement 2025-04-23 (see label)	approved	Apr 23, 2025	openfda
Palbociclib	US FDA	—	Efficacy supplement 2025-04-23 (see label)	approved	Apr 23, 2025	openfda
Palbociclib	US FDA	—	Efficacy supplement 2023-09-06 (see label)	approved	Sep 6, 2023	openfda
Palbociclib	US FDA	—	Efficacy supplement 2023-09-06 (see label)	approved	Sep 6, 2023	openfda
Palbociclib	US FDA	—	Efficacy supplement 2022-12-13 (see label)	approved	Dec 13, 2022	openfda
Palbociclib	US FDA	—	Efficacy supplement 2022-12-13 (see label)	approved	Dec 13, 2022	openfda
Palbociclib	US FDA	Malignant Breast Neoplasm	for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with: o an aromatase inhibitor as initial endocrine-based therapy	approved	Nov 1, 2019	openfda
Palbociclib	US FDA	Malignant Breast Neoplasm	in combination with trastuzumab, with or without pertuzumab, and endocrine therapy for the maintenance treatment of adult patients with HR-positive, HER2‑positive locally advanced or metastatic breast cancer following induction treatment.	approved	Nov 1, 2019	openfda
Palbociclib	US FDA	Malignant Breast Neoplasm	in combination with inavolisib and fulvestrant for the treatment of adult patients with endocrine-resistant, PIK3CA -mutated, HR-positive, HER2-negative, locally advanced or metastatic breast cancer, as detected by an FDA‑authorized test, following recurrence on or after completing adjuvant endocrine therapy.	approved	Nov 1, 2019	openfda
Palbociclib	US FDA	—	; or o fulvestrant in patients with disease progression following endocrine therapy.	approved	Nov 1, 2019	openfda