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

health-canada-dpd

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 101–150 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
NCT04650581	Fulvestrant and Ipatasertib for Advanced HER-2 Negative and Estrogen Receptor Positive (ER+) Breast Cancer Following Progression on First Line CDK 4/6 Inhibitor and Aromatase Inhibitor(FINER)	active not recruiting

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
Palbociclib	CA Health Canada	—	Marketed in Canada as IBRANCE (DIN 02453150) under ATC L01EF01 PALBOCICLIB. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Jun 6, 2024	Apr 20, 2016	health-canada-dpd
Palbociclib	CA Health Canada	—	Marketed in Canada as IBRANCE (DIN 02453177) under ATC L01EF01 PALBOCICLIB. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Jun 6, 2024	Apr 19, 2016	health-canada-dpd
Palbociclib	CA Health Canada	—	Marketed in Canada as IBRANCE (DIN 02453169) under ATC L01EF01 PALBOCICLIB. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Jun 6, 2024	Apr 19, 2016	health-canada-dpd
Palbociclib	CA Health Canada	—	Marketed in Canada as NAT-PALBOCICLIB (DIN 02570157) under ATC L01EF01 PALBOCICLIB. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approved	—	health-canada-dpd
Palbociclib	CA Health Canada	—	Marketed in Canada as NAT-PALBOCICLIB (DIN 02570149) under ATC L01EF01 PALBOCICLIB. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approved	—	health-canada-dpd
Palbociclib	CA Health Canada	—	Marketed in Canada as NAT-PALBOCICLIB (DIN 02570130) under ATC L01EF01 PALBOCICLIB. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approved	—	health-canada-dpd
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
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
Palbociclib	US FDA	—	Efficacy supplement 2019-09-09 (see label)	approved	Sep 9, 2019	openfda
Palbociclib	US FDA	—	Efficacy supplement 2019-04-04 (see label)	approved	Apr 4, 2019	openfda
Palbociclib	US FDA	—	Efficacy supplement 2018-02-06 (see label)	approved	Feb 6, 2018	openfda
Palbociclib	US FDA	—	Efficacy supplement 2017-03-31 (see label)	approved	Mar 31, 2017	openfda
Palbociclib	US FDA	—	Efficacy supplement 2016-02-19 (see label)	approved	Feb 19, 2016	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	Feb 3, 2015	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	Feb 3, 2015	openfda
Palbociclib	US FDA	—	; or o fulvestrant in patients with disease progression following endocrine therapy.	approved	Feb 3, 2015	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	Feb 3, 2015	openfda
Tamoxifen	CA Health Canada	—	Marketed in Canada as TAMOXIFENE - 20 (DIN 02296748) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Jul 27, 2011	Oct 29, 2007	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TAMOXIFENE - 10 (DIN 02296721) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Jul 27, 2011	Oct 29, 2007	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TAMOXIFEN (DIN 02237596) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Oct 25, 2016	Sep 28, 1999	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TAMOXIFEN (DIN 02237597) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Oct 25, 2016	Sep 28, 1999	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as PMS-TAMOXIFEN (DIN 02237459) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Oct 28, 2016	Dec 1, 1998	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as PMS-TAMOXIFEN (DIN 02237460) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Oct 28, 2016	Dec 1, 1998	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TAMONE - (10 MG) (DIN 02063778) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Oct 2, 2007	Dec 31, 1996	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TAMONE - (20 MG) (DIN 02063751) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Oct 2, 2007	Dec 31, 1996	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as NOLVADEX-D TAB 20MG (DIN 02048485) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Mar 22, 2023	Dec 31, 1995	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as MYLAN-TAMOXIFEN (DIN 02088428) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Jan 9, 2017	Dec 31, 1994	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as MYLAN-TAMOXIFEN (DIN 02089858) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Jan 9, 2017	Dec 31, 1994	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as NOLVADEX TAB 10MG (DIN 02048477) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Apr 1, 2003	Dec 31, 1994	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TAMOPLEX TAB 10MG (DIN 01951939) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Sep 9, 1996	Dec 31, 1992	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TAMOPLEX TAB 20MG (DIN 01951947) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Sep 9, 1996	Dec 31, 1992	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TEVA-TAMOXIFEN (DIN 00851965) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approvedsource: Marketed	Dec 31, 1990	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TEVA-TAMOXIFEN (DIN 00851973) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approvedsource: Marketed	Dec 31, 1990	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as APO-TAMOX TAB 10MG (DIN 00812404) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approvedsource: Marketed	Dec 31, 1989	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as TAMONE TAB 20MG (DIN 00810452) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	withdrawnsource: Cancelled Post Marketsince Sep 10, 1996	Dec 31, 1989	health-canada-dpd
Tamoxifen	CA Health Canada	—	Marketed in Canada as APO-TAMOX TAB 20MG (DIN 00812390) under ATC L02BA01 TAMOXIFEN. Indications are not published in the Drug Product Database — see the Health Canada Product Monograph.	approvedsource: Marketed	Dec 31, 1989	health-canada-dpd