Estrogen-receptor positive breast cancer

disease

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Also known as ER+ breast cancerestrogen receptor positive breast canceroestrogen receptor positive breast cancer

Summary

Estrogen-receptor positive breast cancer (MONDO:0006512) is a cancer with 16 cohort genes (115 GWAS associations across 37 studies; 11 CIViC-evidence somatic drivers) and 96 clinical trials. The dominant Reactome pathway is Defective binding of RB1 mutants to E2F1,(E2F2, E2F3) (5 cohort genes). Molecularly, ESR1 D538G confers sensitivity to Elacestrant in Estrogen-receptor Positive Breast Cancer (CIViC Level A); 29 further subtype–drug associations are mapped below. Top therapeutic interventions include tamoxifen, everolimus, and exemestane.

At a glance

Classification: Cancer
Cohort genes: 16
GWAS associations: 115
Clinical trials: 96
Precision-medicine evidence (CIViC): 30 subtype–drug associations

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	estrogen-receptor positive breast cancer
Mondo ID	MONDO:0006512
EFO	EFO:1000649
DOID	DOID:0060075
UMLS	C2938924
MedGen	1843470
Is cancer (heuristic)	yes

Also known as: ER+ breast cancer · estrogen receptor positive breast cancer · oestrogen receptor positive breast cancer

Data availability: 115 GWAS associations (37 studies).

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by etiologic mechanism › cancer or benign tumor › neoplastic disease or syndrome › neoplasm › cancer › carcinoma › breast carcinoma › breast carcinoma by gene expression profile › estrogen-receptor positive breast cancer

Subtypes (2): triple-positive breast carcinoma, hormone receptor-positive breast cancer

Genetics & variants

GWAS landscape

115 GWAS associations across 37 studies. Top hits map to 35 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs13195636	1e-43	HNRNPA1P1 - CD83P1	A
rs67981811	5e-42	ZSCAN12	C
rs10995201	6e-41	LINC02929	A
rs9257566	6e-40	LINC03003	C
rs13195402	3e-39	BTN2A1	G
rs1421085	1e-35	FTO	T
rs8051542	1e-34	TOX3	T
rs78378222	2e-34	TP53	T
rs10035564	1e-27	MRPS30 - HCN1	A
rs13198474	2e-25	SLC17A3	G
rs4821942	2e-23	TNRC6B	A
rs4702	1e-22	FURIN	G
rs2965183	2e-21	GATAD2A	G
rs10828248	5e-21	MLLT10	A
rs4321976	1e-16	HNF4G - RNU2-54P	T
rs7447717	8e-16	HCN1 - EMB	A
rs61863443	1e-15	ZNF365 - LINC02929	G
rs45512493	3e-15	TOX3	A
rs2532363	4e-15	MAPK8IP1P1 - ARL17B	G
rs179444	1e-14	TRPS1	G
rs1724390	2e-14	DND1P1	C
rs75905550	6e-14	GNAI2P1 - RPL30P11	G
rs6805189	6e-14	FOXP1	T
rs4784227	1e-13	CASC16	T	1.33
rs16991615	2e-13	MCM8	A
rs2957468	2e-13	ZFPM2	A
rs9475034	7e-13	RNU6-1023P - FAM83B	A
rs199498	1e-12	WNT3	T
rs7907439	1e-12	LINC02929	C
rs35840638	2e-12	ADAP2	A

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST90651105	Wu X	2023	69,501	105,974	Using human genetics to understand the phenotypic association between chronotype and breast cancer.
GCST90026468	Adedokun B	2021	69,501	105,974	Cross-ancestry GWAS meta-analysis identifies six breast cancer loci in African and European ancestry women.
GCST90319500	Tang M	2023	53,386	183,232	Epidemiological and Genetic Analyses of Schizophrenia and Breast Cancer.
GCST90321111	Middha P	2023	50,215	80,354	A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
GCST90321112	Middha P	2023	50,215	80,354	A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
GCST90321113	Middha P	2023	50,215	80,354	A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
GCST90321114	Middha P	2023	50,215	80,354	A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
GCST90321115	Middha P	2023	50,215	80,354	A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
GCST90321116	Middha P	2023	50,215	80,354	A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.
GCST90321117	Middha P	2023	50,215	80,354	A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	3
Tier 2: splice/UTR	4
Tier 3: regulatory	1
Tier 4: intronic/intergenic	42

MAF distribution

Bucket	Variants
common (>=0.05)	47
low_freq (0.01-0.05)	1
rare (<0.01)	0
unknown	2

Functional consequences

Consequence	Count
intron_variant	33
intergenic_variant	8
3_prime_UTR_variant	3
missense_variant	2
stop_gained	1
5_prime_UTR_variant	1
regulatory_region_variant	1
non_coding_transcript_exon_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs13195636	6	27541714	A>C,G	0.05	intron_variant	HNRNPA1P1 - CD83P1	1e-43	Tier 4: intronic/intergenic
rs67981811	6	28387058	C>G	0.05	3_prime_UTR_variant	ZSCAN12	5e-42	Tier 2: splice/UTR
rs10995201	10	62540131	A>G	0.05	intron_variant	LINC02929	6e-41	Tier 4: intronic/intergenic
rs9257566	6	29176755	C>A,G,T	0.05	intergenic_variant	LINC03003	6e-40	Tier 4: intronic/intergenic
rs13195402	6	26463347	G>A,C,T	0.05	stop_gained	BTN2A1	3e-39	Tier 1: coding
rs1421085	16	53767042	T>C	0.05	intron_variant	FTO	1e-35	Tier 4: intronic/intergenic
rs8051542	16	52500255	T>C,G	0.05	intron_variant	TOX3	1e-34	Tier 4: intronic/intergenic
rs78378222	17	7668434	T>A,G		3_prime_UTR_variant	TP53	2e-34	Tier 2: splice/UTR
rs10035564	5	45252398	A>G,T	0.05	intergenic_variant	MRPS30 - HCN1	1e-27	Tier 4: intronic/intergenic
rs13198474	6	25874195	G>A,T	0.05	5_prime_UTR_variant	SLC17A3	2e-25	Tier 2: splice/UTR
rs4821942	22	40322096	G>A,C	0.05	intron_variant	TNRC6B	2e-23	Tier 4: intronic/intergenic
rs4702	15	90883330	G>A,C	0.05	3_prime_UTR_variant	FURIN	1e-22	Tier 2: splice/UTR
rs2965183	19	19434887	G>A,C,T	0.05	intron_variant	GATAD2A	2e-21	Tier 4: intronic/intergenic
rs10828248	10	21535690	A>G	0.05	intron_variant	MLLT10	5e-21	Tier 4: intronic/intergenic
rs4321976	8	75702723	T>C	0.05	regulatory_region_variant	HNF4G - RNU2-54P	1e-16	Tier 3: regulatory
rs7447717	5	45770150	A>G	0.05	intergenic_variant	HCN1 - EMB	8e-16	Tier 4: intronic/intergenic
rs61863443	10	62495224	G>A	0.05	intron_variant	ZNF365 - LINC02929	1e-15	Tier 4: intronic/intergenic
rs45512493	16	52525814	A>G	0.05	intron_variant	TOX3	3e-15	Tier 4: intronic/intergenic
rs2532363	17	46256057	G>T	0.05	intron_variant	MAPK8IP1P1 - ARL17B	4e-15	Tier 4: intronic/intergenic
rs179444	8	115660520	G>T	0.05	intron_variant	TRPS1	1e-14	Tier 4: intronic/intergenic
rs1724390	17	45585881	C>A,T	0.05	non_coding_transcript_exon_variant	DND1P1	2e-14	Tier 4: intronic/intergenic
rs75905550	12	14255620	G>C,T	0.05	intergenic_variant	GNAI2P1 - RPL30P11	6e-14	Tier 4: intronic/intergenic
rs6805189	3	71482962	T>A,C,G	0.05	intron_variant	FOXP1	6e-14	Tier 4: intronic/intergenic
rs4784227	16	52565276	C>A,T	0.06	intron_variant	CASC16	1e-13	Tier 4: intronic/intergenic
rs16991615	20	5967581	G>A	0.05	missense_variant	MCM8	2e-13	Tier 1: coding
rs2957468	8	105313132	A>C,G	0.05	intergenic_variant	ZFPM2	2e-13	Tier 4: intronic/intergenic
rs9475034	6	54837491	A>G	0.05	intergenic_variant	RNU6-1023P - FAM83B	7e-13	Tier 4: intronic/intergenic
rs199498	17	46788237	T>A,C,G	0.05	intron_variant	WNT3	1e-12	Tier 4: intronic/intergenic
rs7907439	10	62586891	C>T	0.05	intron_variant	LINC02929	1e-12	Tier 4: intronic/intergenic
rs35840638	17	30924623	G>A	0.05	intron_variant	ADAP2	2e-12	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 61 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
AURKA			CIViC #61
CCND1	Act	HNSC,PCM,UCEC	CIViC #8
CCNE1			CIViC #11
CDK4	LoF	MEL	CIViC #13
CDK6			CIViC #12
ESR1	Act	BRCA,LUSC,MEL,UCEC	CIViC #21
FGFR1	Act	BLCA,GBM,OVT,PANCREAS,PAST,PGNG,WDTC	CIViC #1885
MMP1			CIViC #3548
PIK3CA	Act	ACYC,ANGS,ANSC,BCC,BLADDER,BLCA,BRCA,CCRCC,CEAD,CESC,CHOL,COAD,COADREAD,EPM,ESCA,ESCC,GB,GBM,HCC,HGGNOS,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MBL,MGCT,NPC,NSCLC,OVT,PAAD,PAST,PLMESO,PRAD,PRCC,PROSTATE,RCC,SACA,SKCM,SOFT_TISSUE,STAD,UCEC,UCS,UTUC,VULVA,WDTC	CIViC #37
RB1	LoF	ACC,BLADDER,BLCA,BRCA,CESC,ESCA,GB,GBM,GIST,HCC,HNSC,LGGNOS,LIPO,LMS,LUAD,LUSC,MEL,MT,NSCLC,OS,OVT,PANCREAS,PCM,PRAD,PROSTATE,RBL,SCLC,SKCM,SOFT_TISSUE,STAD,STOMACH,UCEC,UCS	CIViC #4795
FGFR2	Act	BRCA,CHOL,LUSC,SACA,UCEC	CIViC #22

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CCND1	Orphanet:29073	Multiple myeloma
CCND1	Orphanet:52416	Mantle cell lymphoma
CCND1	Orphanet:67038	B-cell chronic lymphocytic leukemia
CCND1	Orphanet:892	Von Hippel-Lindau disease
CDK4	Orphanet:618	Familial melanoma
CDK4	Orphanet:99970	Dedifferentiated liposarcoma
CDK4	Orphanet:99971	Well-differentiated liposarcoma
CDK6	Orphanet:2512	Autosomal recessive primary microcephaly
ESR1	Orphanet:785	Estrogen resistance syndrome
FGFR1	Orphanet:168953	Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement
FGFR1	Orphanet:2117	Hartsfield syndrome
FGFR1	Orphanet:220386	Semilobar holoprosencephaly
FGFR1	Orphanet:2396	Encephalocraniocutaneous lipomatosis
FGFR1	Orphanet:251576	Gliosarcoma
FGFR1	Orphanet:251579	Giant cell glioblastoma
FGFR1	Orphanet:251615	Pilomyxoid astrocytoma
FGFR1	Orphanet:2645	Osteoglosphonic dysplasia
FGFR1	Orphanet:280200	Microform holoprosencephaly
FGFR1	Orphanet:314950	Primary hypereosinophilic syndrome
FGFR1	Orphanet:3157	Septo-optic dysplasia spectrum
FGFR1	Orphanet:3366	Non-syndromic metopic craniosynostosis
FGFR1	Orphanet:432	Normosmic congenital hypogonadotropic hypogonadism
FGFR1	Orphanet:478	Kallmann syndrome
FGFR1	Orphanet:93258	Pfeiffer syndrome type 1
FGFR1	Orphanet:93924	Lobar holoprosencephaly
FGFR1	Orphanet:99798	Oligodontia
MMP1	Orphanet:79408	Autosomal recessive generalized dystrophic epidermolysis bullosa, severe form
PIK3CA	Orphanet:140944	CLOVES syndrome
PIK3CA	Orphanet:144	Lynch syndrome
PIK3CA	Orphanet:168984	CLAPO syndrome
PIK3CA	Orphanet:201	Cowden syndrome
PIK3CA	Orphanet:210159	Adult hepatocellular carcinoma
PIK3CA	Orphanet:221061	Familial cerebral cavernous malformation
PIK3CA	Orphanet:2495	Meningioma
PIK3CA	Orphanet:276280	Hemihyperplasia-multiple lipomatosis syndrome
PIK3CA	Orphanet:295239	Macrodactyly of fingers, unilateral
PIK3CA	Orphanet:295243	Macrodactyly of toes, unilateral
PIK3CA	Orphanet:314662	Segmental progressive overgrowth syndrome with fibroadipose hyperplasia
PIK3CA	Orphanet:60040	Megalencephaly-capillary malformation-polymicrogyria syndrome
PIK3CA	Orphanet:714737	Diffuse capillary malformation with overgrowth
PIK3CA	Orphanet:90308	Capillary-lymphatic-venous malformation with segmental distribution
PIK3CA	Orphanet:99802	Hemimegalencephaly
RB1	Orphanet:1587	Monosomy 13q14 syndrome
RB1	Orphanet:357027	Hereditary retinoblastoma
RB1	Orphanet:357034	Non-hereditary retinoblastoma
RB1	Orphanet:668	Osteosarcoma
RB1	Orphanet:70573	Small cell lung cancer
RHOBTB2	Orphanet:1934	Early infantile developmental and epileptic encephalopathy
RHOBTB2	Orphanet:2131	Alternating hemiplegia of childhood
FGFR2	Orphanet:1540	Jackson-Weiss syndrome

Cohort genes → proteins

16 cohort genes, 14 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	6
civic_only	10

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
AURKA	HGNC:11393	ENSG00000087586	O14965	Aurora kinase A	civic_evidence
CCND1	HGNC:1582	ENSG00000110092	P24385	G1/S-specific cyclin-D1	civic_evidence
CCNE1	HGNC:1589	ENSG00000105173	P24864	G1/S-specific cyclin-E1	civic_evidence
CDK4	HGNC:1773	ENSG00000135446	P11802	Cyclin-dependent kinase 4	civic_evidence
CDK6	HGNC:1777	ENSG00000105810	Q00534	Cyclin-dependent kinase 6	civic_evidence
ESR1	HGNC:3467	ENSG00000091831	P03372	Estrogen receptor	civic_evidence
FGFR1	HGNC:3688	ENSG00000077782	P11362	Fibroblast growth factor receptor 1	civic_evidence
MMP1	HGNC:7155	ENSG00000196611	P03956	Interstitial collagenase	civic_evidence
PIK3CA	HGNC:8975	ENSG00000121879	P42336	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	civic_evidence
RB1	HGNC:9884	ENSG00000139687	P06400	Retinoblastoma-associated protein	civic_evidence
PDLIM2	HGNC:13992	ENSG00000120913	Q96JY6	PDZ and LIM domain protein 2	gwas
RHOBTB2	HGNC:18756	ENSG00000008853	Q9BYZ6	Rho-related BTB domain-containing protein 2	gwas
ZNF613	HGNC:25827	ENSG00000176024	Q6PF04	Zinc finger protein 613	gwas
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	gwas
CASC16	HGNC:48608	ENSG00000249231		cancer susceptibility 16	gwas
RAB9BP1	HGNC:9793	ENSG00000232159		RAB9B, member RAS oncogene family pseudogene 1	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
AURKA	Aurora kinase A	Mitotic serine/threonine kinase that contributes to the regulation of cell cycle progression.
CCND1	G1/S-specific cyclin-D1	Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition.
CCNE1	G1/S-specific cyclin-E1	Essential for the control of the cell cycle at the G1/S (start) transition.
CDK4	Cyclin-dependent kinase 4	Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G(1)/S transition.
CDK6	Cyclin-dependent kinase 6	Serine/threonine-protein kinase involved in the control of the cell cycle and differentiation; promotes G1/S transition.
ESR1	Estrogen receptor	Nuclear hormone receptor.
FGFR1	Fibroblast growth factor receptor 1	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation and migration.
MMP1	Interstitial collagenase	Cleaves collagens of types I, II, and III at one site in the helical domain.
PIK3CA	Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform	Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.
RB1	Retinoblastoma-associated protein	Tumor suppressor that is a key regulator of the G1/S transition of the cell cycle.
PDLIM2	PDZ and LIM domain protein 2	Probable adapter protein located at the actin cytoskeleton that promotes cell attachment.
RHOBTB2	Rho-related BTB domain-containing protein 2	Regulator of cell proliferation and apoptosis.
ZNF613	Zinc finger protein 613	May be involved in transcriptional regulation.
FGFR2	Fibroblast growth factor receptor 2	Tyrosine-protein kinase that acts as a cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic de…

Protein-family classification

Druggable: 8 · Difficult: 2 · Unknown: 6 · Druggable fraction: 0.5

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Kinase	6	10.4×	6e-05
Nuclear receptor	1	24.1×	0.102
Protease	1	2.3×	0.597
Transcription factor	2	1.0×	0.742
Other/Unknown	6	0.7×	0.958

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
AURKA	Kinase	yes	2.7.11.1	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CCND1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CCNE1	Other/Unknown	no		Cyclin_C-dom, Cyclin_N, Cyclin-like_dom
CDK4	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
CDK6	Kinase	yes	2.7.11.22	Prot_kinase_dom, Ser/Thr_kinase_AS, Kinase-like_dom_sf
ESR1	Nuclear receptor	yes		Nucl_hrmn_rcpt_lig-bd, Estr_rcpt, Znf_hrmn_rcpt
FGFR1	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
MMP1	Protease	yes	3.4.24.7	Hemopexin-like_dom, Pept_M10_metallopeptidase, Peptidoglycan-bd-like
PIK3CA	Kinase	yes	2.7.1.137	PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom
RB1	Other/Unknown	no		RB_B, RB_A, Cyclin-like_dom
PDLIM2	Transcription factor	no		PDZ, Znf_LIM, PDLI1-4/Zasp-like_mid
RHOBTB2	Other/Unknown	no		BTB/POZ_dom, Small_GTPase, Small_GTPase_Rho
ZNF613	Transcription factor	no		KRAB, Znf_C2H2_type, KRAB_dom_sf
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2
CASC16	Other/Unknown	no
RAB9BP1	Other/Unknown	no

Expression context

Cohort genes with no expression data: 0.

14 cohort genes are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	1
broad (>20)	15
unknown	0

Top tissues across cohort

Tissue	Cohort genes
ventricular zone	3
adrenal tissue	3
male germ line stem cell (sensu Vertebrata) in testis	3
oocyte	2
secondary oocyte	2
stromal cell of endometrium	2
calcaneal tendon	2
endometrium epithelium	1
upper arm skin	1
embryo	1
ganglionic eminence	1
pylorus	1
trabecular bone tissue	1
cervix epithelium	1
mammalian vulva	1
oviduct epithelium	1
buccal mucosa cell	1
epithelial cell of pancreas	1
islet of Langerhans	1
pancreatic ductal cell	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
AURKA	236	ubiquitous	marker	oocyte, secondary oocyte, ventricular zone
CCND1	280	ubiquitous	marker	endometrium epithelium, stromal cell of endometrium, upper arm skin
CCNE1	201	ubiquitous	marker	secondary oocyte, oocyte, adrenal tissue
CDK4	138	ubiquitous	marker	embryo, ganglionic eminence, ventricular zone
CDK6	262	ubiquitous	marker	adrenal tissue, trabecular bone tissue, pylorus
ESR1	216	broad	marker	oviduct epithelium, cervix epithelium, mammalian vulva
FGFR1	292	ubiquitous	marker	buccal mucosa cell, stromal cell of endometrium, calcaneal tendon
MMP1	172	broad	marker	epithelial cell of pancreas, pancreatic ductal cell, islet of Langerhans
PIK3CA	284	ubiquitous	marker	calcaneal tendon, adrenal tissue, tendon
RB1	287	ubiquitous	marker	epithelium of nasopharynx, choroid plexus epithelium, visceral pleura
PDLIM2	281	ubiquitous	marker	spleen, pharyngeal mucosa, lower esophagus mucosa
RHOBTB2	213	ubiquitous	marker	upper lobe of left lung, upper lobe of lung, right frontal lobe
ZNF613	168	ubiquitous	yes	primordial germ cell in gonad, ventricular zone, male germ line stem cell (sensu Vertebrata) in testis
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum
CASC16	115	tissue_specific	marker	male germ line stem cell (sensu Vertebrata) in testis, sperm, left testis
RAB9BP1	9		yes	male germ line stem cell (sensu Vertebrata) in testis, skin of hip, Brodmann (1909) area 46

Protein interactions among cohort

Intra-cohort edges: 12.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ESR1	12,382
CDK4	8,412
CCND1	8,328
CDK6	6,767
AURKA	6,376
FGFR1	5,693
PIK3CA	5,157
RB1	4,374
CCNE1	3,811
MMP1	2,933

Intra-cohort edges

A	B	Sources
CCND1	CDK4	biogrid_interaction, intact, string_interaction
CCND1	CDK6	intact, string_interaction
CCND1	ESR1	string_interaction
CCND1	RB1	string_interaction
CCNE1	CDK4	string_interaction
CCNE1	CDK6	string_interaction
CDK4	CDK6	string_interaction
CDK4	RB1	biogrid_interaction, string_interaction
CDK6	RB1	biogrid_interaction, string_interaction
FGFR1	FGFR2	intact
FGFR2	PDLIM2	biogrid_interaction
FGFR2	RHOBTB2	biogrid_interaction, intact

Structural data

PDB: 12 · AlphaFold-only: 2 · No structure: 2

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ESR1	P03372	478
AURKA	O14965	193
PIK3CA	P42336	135
FGFR1	P11362	83
FGFR2	P21802	63
CCNE1	P24864	22
CDK6	Q00534	22
RB1	P06400	19
CDK4	P11802	15
MMP1	P03956	15
CCND1	P24385	11
PDLIM2	Q96JY6	2

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
RHOBTB2	Q9BYZ6	81.89
ZNF613	Q6PF04	66.56

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 224. Enrichment computed across 16 evidence-associated genes (13 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 13 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Defective binding of RB1 mutants to E2F1,(E2F2, E2F3)	5	244.0×	2e-09	CCND1, CCNE1, CDK4, CDK6, RB1
Aberrant regulation of mitotic G1/S transition in cancer due to RB1 defects	4	270.3×	8e-08	CCND1, CCNE1, CDK4, CDK6
Cyclin D associated events in G1	5	89.6×	1e-07	CCND1, CCNE1, CDK4, CDK6, RB1
Drug-mediated inhibition of CDK4/CDK6 activity	3	527.1×	6e-07	CCND1, CDK4, CDK6
PTK6 Regulates Cell Cycle	3	439.2×	7e-07	CCND1, CCNE1, CDK4
Aberrant regulation of mitotic cell cycle due to RB1 defects	4	125.5×	7e-07	CCND1, CCNE1, CDK4, CDK6
G1 Phase	4	121.2×	7e-07	CCND1, CCNE1, CDK4, CDK6
Diseases of mitotic cell cycle	4	121.2×	7e-07	CCND1, CCNE1, CDK4, CDK6
Cyclin E associated events during G1/S transition	4	87.8×	2e-06	CCND1, CCNE1, CDK4, RB1
Cyclin A:Cdk2-associated events at S phase entry	4	81.7×	3e-06	CCND1, CCNE1, CDK4, RB1
Mitotic G1 phase and G1/S transition	4	56.7×	1e-05	CCND1, CCNE1, CDK4, CDK6
Signaling by PTK6	3	125.5×	3e-05	CCND1, CCNE1, CDK4
Signaling by Non-Receptor Tyrosine Kinases	3	125.5×	3e-05	CCND1, CCNE1, CDK4
Constitutive Signaling by Aberrant PI3K in Cancer	4	39.0×	4e-05	ESR1, FGFR1, FGFR2, PIK3CA
Diseases of Cellular Senescence	2	585.6×	4e-05	CDK4, CDK6
Evasion of Oncogene Induced Senescence Due to p16INK4A Defects	2	585.6×	4e-05	CDK4, CDK6
Evasion of Oncogene Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	2	585.6×	4e-05	CDK4, CDK6
Evasion of Oxidative Stress Induced Senescence Due to p16INK4A Defects	2	585.6×	4e-05	CDK4, CDK6
Evasion of Oxidative Stress Induced Senescence Due to Defective p16INK4A binding to CDK4 and CDK6	2	585.6×	4e-05	CDK4, CDK6
Diseases of cellular response to stress	2	585.6×	4e-05	CDK4, CDK6
Cell Cycle, Mitotic	5	18.5×	4e-05	AURKA, CCND1, CCNE1, CDK4, CDK6
Phosphorylation of proteins involved in G1/S transition by active Cyclin E:Cdk2 complexes	2	439.2×	7e-05	CCNE1, RB1
Oncogene Induced Senescence	3	77.5×	7e-05	CDK4, CDK6, RB1
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	4	29.8×	7e-05	ESR1, FGFR1, FGFR2, PIK3CA
PI3K Cascade	3	62.8×	1e-04	FGFR1, FGFR2, PIK3CA
Cell Cycle	5	13.9×	1e-04	AURKA, CCND1, CCNE1, CDK4, CDK6
G1/S Transition	3	53.8×	2e-04	CCND1, CCNE1, CDK4
SCF(Skp2)-mediated degradation of p27/p21	3	47.9×	2e-04	CCND1, CCNE1, CDK4
PIP3 activates AKT signaling	4	20.6×	2e-04	ESR1, FGFR1, FGFR2, PIK3CA
S Phase	3	41.8×	3e-04	CCND1, CCNE1, CDK4

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 14 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
G1/S transition of mitotic cell cycle	5	71.7×	2e-06	CCND1, CCNE1, CDK4, CDK6, RB1
regulation of G2/M transition of mitotic cell cycle	3	277.8×	2e-05	AURKA, CDK4, CDK6
cell division	6	19.8×	3e-05	AURKA, CCND1, CCNE1, CDK4, CDK6, RB1
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	2	802.5×	1e-04	FGFR1, FGFR2
prostate epithelial cord elongation	2	802.5×	1e-04	ESR1, FGFR2
ventricular zone neuroblast division	2	601.9×	2e-04	FGFR1, FGFR2
negative regulation of transcription by RNA polymerase II	7	8.9×	2e-04	CCND1, CCNE1, CDK6, ESR1, FGFR1, FGFR2, RB1
positive regulation of phospholipase activity	2	481.5×	3e-04	FGFR1, FGFR2
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	2	343.9×	5e-04	ESR1, FGFR2
positive regulation of fibroblast proliferation	3	63.4×	5e-04	CDK4, CDK6, ESR1
lung-associated mesenchyme development	2	240.7×	1e-03	FGFR1, FGFR2
negative regulation of gene expression	4	19.7×	0.001	AURKA, ESR1, PIK3CA, RB1
branching involved in salivary gland morphogenesis	2	200.6×	0.001	FGFR1, FGFR2
mammary gland alveolus development	2	141.6×	0.002	CCND1, ESR1
protein autophosphorylation	3	31.1×	0.003	AURKA, FGFR1, FGFR2
phosphatidylinositol-mediated signaling	2	100.3×	0.004	FGFR1, PIK3CA
positive regulation of cardiac muscle cell proliferation	2	89.2×	0.004	FGFR1, FGFR2
positive regulation of mesenchymal cell proliferation	2	86.0×	0.004	FGFR1, FGFR2
positive regulation of G2/M transition of mitotic cell cycle	2	86.0×	0.004	CCND1, CDK4
midbrain development	2	86.0×	0.004	FGFR1, FGFR2
digestive tract development	2	75.2×	0.006	FGFR2, RB1
liver regeneration	2	73.0×	0.006	AURKA, CCND1
skeletal system morphogenesis	2	70.8×	0.006	FGFR1, FGFR2
ureteric bud development	2	65.1×	0.007	FGFR1, FGFR2
peptidyl-tyrosine phosphorylation	2	60.2×	0.007	FGFR1, FGFR2
positive regulation of G1/S transition of mitotic cell cycle	2	57.3×	0.008	CCND1, CCNE1
response to muscle inactivity	1	1203.7×	0.009	PIK3CA
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	1203.7×	0.009	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	1203.7×	0.009	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	1203.7×	0.009	FGFR2

Therapeutics

Drug target analysis

Approved (phase 4): 10 · Phase ≥3: 10 · Phased (≥1): 11 · Undrugged: 5

Druggability breadth: 11 of 16 evidence-associated genes (69%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Genes with an approved drug

The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.

Symbol	Example approved molecule
AURKA	INAMRINONE
CCND1	PALBOCICLIB
CCNE1	PALBOCICLIB
CDK4	PALBOCICLIB
CDK6	PALBOCICLIB
ESR1	CANDESARTAN CILEXETIL
FGFR1	PONATINIB
MMP1	TILUDRONATE DISODIUM
PIK3CA	IDELALISIB
FGFR2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ESR1	162	4
FGFR1	93	4
PIK3CA	67	4
AURKA	65	4
FGFR2	59	4
CDK4	56	4
CDK6	45	4
CCNE1	38	4
CCND1	35	4
MMP1	21	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
INAMRINONE	4	AURKA
FEDRATINIB	4	AURKA, CDK4, FGFR1, FGFR2, PIK3CA
AXITINIB	4	AURKA, FGFR1, FGFR2
SORAFENIB	4	AURKA, CDK6, FGFR1, FGFR2
NICLOSAMIDE	4	AURKA, FGFR1
ENTRECTINIB	4	AURKA, FGFR1
FOSTAMATINIB	4	AURKA
CABOZANTINIB	4	AURKA, FGFR1
GILTERITINIB	4	AURKA, CCNE1, CDK4
BRIGATINIB	4	AURKA, FGFR1, FGFR2
UPADACITINIB	4	AURKA, FGFR1
SULFADIAZINE	4	AURKA
PAZOPANIB	4	AURKA, FGFR1, FGFR2
DOXORUBICIN	4	AURKA, ESR1
SUNITINIB	4	AURKA, CDK4, FGFR1, FGFR2, PIK3CA
DASATINIB	4	AURKA, FGFR1, FGFR2, PIK3CA
ERLOTINIB	4	AURKA, FGFR2
CRIZOTINIB	4	AURKA, PIK3CA
MIDOSTAURIN	4	AURKA, FGFR1, FGFR2, PIK3CA
PALBOCICLIB	4	CCND1, CCNE1, CDK4, CDK6
ABEMACICLIB	4	CCND1, CCNE1, CDK4, CDK6
RIBOCICLIB	4	CCND1, CDK4, CDK6
TRILACICLIB	4	CCND1, CCNE1, CDK4, CDK6
DABRAFENIB	4	CDK4, CDK6
CERITINIB	4	CDK4, FGFR2
ENCORAFENIB	4	CDK4
NINTEDANIB	4	CDK4, FGFR1, FGFR2
MOMELOTINIB	4	CDK6
OLAPARIB	4	CDK6
CANDESARTAN CILEXETIL	4	ESR1

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 7.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
ESR1	2,435	Binding:2037, Functional:363, ADMET:35
PIK3CA	2,034	Binding:2009, ADMET:19, Toxicity:4, Functional:2
AURKA	1,500	Binding:1483, Functional:10, ADMET:7
FGFR1	1,465	Binding:1428, Functional:24, ADMET:13
CDK4	1,142	Binding:1086, Functional:53, ADMET:2, Toxicity:1
FGFR2	966	Binding:940, Functional:22, ADMET:4
CDK6	715	Binding:691, Functional:24
CCNE1	691	Binding:690, ADMET:1
MMP1	588	Binding:574, ADMET:10, Functional:3, Toxicity:1
CCND1	576	Binding:574, Functional:1, ADMET:1
RB1	59	Binding:59

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
AURKA	2.7.11.1	non-specific serine/threonine protein kinase
CDK4	2.7.11.22	cyclin-dependent kinase
CDK6	2.7.11.22	cyclin-dependent kinase
FGFR1	2.7.10.1	receptor protein-tyrosine kinase
MMP1	3.4.24.7	interstitial collagenase
PIK3CA	2.7.1.137, 2.7.1.153, 2.7.11.1	phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase
FGFR2	2.7.10.1	receptor protein-tyrosine kinase

Cohort genes with high screening signal

≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.

Symbol	ChEMBL assays
AURKA	1,500
CCND1	576
CCNE1	691
CDK4	1,142
CDK6	715
ESR1	2,435
FGFR1	1,465
MMP1	588
PIK3CA	2,034
FGFR2	966

Pharmacogenomics

Cohort genes with a PharmGKB record: 15; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Drug repurposing candidates

27 approved/phased drugs hit cohort targets but don’t yet appear in disease-level clinical trials. Target-inhibition rationale is strongest for cancer driver genes; a bioactivity hit is a screening signal, not a treatment claim.

Compound	Max phase	Cohort target (bioactivity)
INAMRINONE	4	AURKA
FEDRATINIB	4	AURKA, CDK4, FGFR1, FGFR2, PIK3CA
AXITINIB	4	AURKA, FGFR1, FGFR2
SORAFENIB	4	AURKA, CDK6, FGFR1, FGFR2
NICLOSAMIDE	4	AURKA, FGFR1
FOSTAMATINIB	4	AURKA
CABOZANTINIB	4	AURKA, FGFR1
GILTERITINIB	4	AURKA, CCNE1, CDK4
BRIGATINIB	4	AURKA, FGFR1, FGFR2
UPADACITINIB	4	AURKA, FGFR1
SULFADIAZINE	4	AURKA
PAZOPANIB	4	AURKA, FGFR1, FGFR2
DOXORUBICIN	4	AURKA, ESR1
SUNITINIB	4	AURKA, CDK4, FGFR1, FGFR2, PIK3CA
DASATINIB	4	AURKA, FGFR1, FGFR2, PIK3CA
ERLOTINIB	4	AURKA, FGFR2
CRIZOTINIB	4	AURKA, PIK3CA
MIDOSTAURIN	4	AURKA, FGFR1, FGFR2, PIK3CA
ABEMACICLIB	4	CCND1, CCNE1, CDK4, CDK6
TRILACICLIB	4	CCND1, CCNE1, CDK4, CDK6
DABRAFENIB	4	CDK4, CDK6
CERITINIB	4	CDK4, FGFR2
ENCORAFENIB	4	CDK4
NINTEDANIB	4	CDK4, FGFR1, FGFR2
MOMELOTINIB	4	CDK6
OLAPARIB	4	CDK6
CANDESARTAN CILEXETIL	4	ESR1

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	10	AURKA, CCND1, CCNE1, CDK4, CDK6, ESR1, FGFR1, MMP1, PIK3CA, FGFR2
B	Phased (≥1) drug, not yet approved	1	RB1
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	5	PDLIM2, RHOBTB2, ZNF613, CASC16, RAB9BP1

Undrugged target profiles

5 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
PDLIM2	0	—
RHOBTB2	0	—
ZNF613	0	—
CASC16	0	—
RAB9BP1	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 96.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	50
Not specified	22
PHASE1	9
PHASE1/PHASE2	8
PHASE3	4
EARLY_PHASE1	2
PHASE4	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05525481	PHASE4	UNKNOWN	Tamoxifen Prediction Study in Patients With ER+ Breast Cancer
NCT01953588	PHASE3	ACTIVE_NOT_RECRUITING	Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery
NCT02947685	PHASE3	ACTIVE_NOT_RECRUITING	Randomized, Open Label, Clinical Study of the Targeted Therapy, Palbociclib, to Treat Metastatic Breast Cancer
NCT06407401	PHASE3	NOT_YET_RECRUITING	Improvement of Quality of Life Through Supportive Treatments for Hormone Therapy - Related Symptoms in Patients With Early Breast Cancer
NCT00066690	PHASE3	COMPLETED	Suppression of Ovarian Function With Either Tamoxifen or Exemestane Compared With Tamoxifen Alone in Treating Premenopausal Women With Hormone-Responsive Breast Cancer
NCT01984138	PHASE2	ACTIVE_NOT_RECRUITING	REVIVE: Replens Versus Intra-Vaginal Estrogen for the Treatment of Vaginal Dryness on Aromatase Inhibitor Therapy
NCT01992952	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fulvestrant +/- Akt Inhibition in Advanced Aromatase Inhibitor Resistant Breast Cancer
NCT02238808	PHASE2	ACTIVE_NOT_RECRUITING	A Study to See Whether Estrogen Can Slow the Growth of Some ER Positive Breast Cancers
NCT02957968	PHASE2	ACTIVE_NOT_RECRUITING	Neoadjuvant Pembrolizumab + Decitabine Followed by Std Neoadj Chemo for Locally Advanced HER2- Breast Ca
NCT04920708	PHASE2	ACTIVE_NOT_RECRUITING	Fulvestrant, Ipatasertib and CDK4/6 Inhibition in Metastatic ER+/HER2- Breast Cancer Patients Without ctDNA Suppression
NCT04985266	PHASE2	RECRUITING	A Trial of Early Detection of Molecular Relapse With Circulating Tumour DNA Tracking and Treatment With Palbociclib Plus Fulvestrant Versus Standard Endocrine Therapy in Patients With ER Positive HER2 Negative Breast Cancer
NCT05020860	PHASE2	RECRUITING	Correlation of Clinical Response to Pathologic Response in Patients With Early Breast Cancer
NCT05490472	PHASE1/PHASE2	RECRUITING	JAB-2485 Activity in Adult Patients With Advanced Solid Tumors
NCT05534438	PHASE2	RECRUITING	A Study on Adding Precisely Targeted Radiation Therapy (Stereotactic Body Radiation Therapy) to the Usual Treatment Approach (Drug Therapy) in People With Breast Cancer
NCT05607004	PHASE2	RECRUITING	(Z)-Endoxifen for the Treatment of Premenopausal Women With ER+/HER2- Breast Cancer
NCT06062498	PHASE2	RECRUITING	Elacestrant vs Elacestrant Plus a CDK4/6 Inhibitor in Patients With ERpositive/HER2-negative Advanced or Metastatic Breast Cancer
NCT06150898	PHASE2	RECRUITING	Ketorolac and Pregabalin Effects on breaSt Cancer (KePreSt)
NCT06395519	PHASE1/PHASE2	RECRUITING	A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies
NCT06439693	PHASE2	RECRUITING	The SAPPHO Study: Sequential Therapy With Curative Intent in de Novo HER2+ Metastatic Breast Cancer
NCT06525766	PHASE2	RECRUITING	Adaptive Therapy With Capecitabine for Treatment of Metastatic ER Positive, HER2 Negative Breast Cancer
NCT06590857	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Trial of 225Ac-DOTATATE (RYZ101) in Subjects With ER+, HER2-negative Unresectable or Metastatic Breast Cancer Expressing SSTRs.
NCT06923527	PHASE2	RECRUITING	Circulating Tumor DNA
NCT07002177	PHASE1/PHASE2	RECRUITING	A Phase Ib/II Study to Evaluate Multiple Combination Therapies of FWD1802 in Patients With ER+/HER2- BC
NCT07222215	PHASE2	RECRUITING	PhII Randomized CAPecitabine + ELAcestrant vs. Capecitabine Alone in ER+ Breast Cancer (CAPELA)
NCT07340541	PHASE2	RECRUITING	Evolutionary Clinical Trial for Novel Biomarker-Driven Therapies
NCT07483307	PHASE2	RECRUITING	A Study of the Impact of Endocrine Therapy on Surgical Outcomes in People With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00003199	PHASE2	COMPLETED	Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer
NCT00057941	PHASE2	COMPLETED	Anastrozole and ZD1839 Compared With Fulvestrant and ZD1839 in Postmenopausal Women w/ Metastatic Breast Cancer
NCT00082810	PHASE2	COMPLETED	Tipifarnib and Fulvestrant in Hormone Receptor-Positive Metastatic Breast Cancer
NCT00194779	PHASE2	COMPLETED	Combination Chemotherapy and Filgrastim Before Surgery in Treating Patients With HER2-Positive Breast Cancer That Can Be Removed By Surgery
NCT00194792	PHASE2	TERMINATED	Hormone Therapy and Combination Chemotherapy Before and After Surgery in Treating Patients With Stage I-IIIA Breast Cancer
NCT00407888	PHASE2	COMPLETED	Doxorubicin Hydrochloride, Cyclophosphamide, and Filgrastim Followed By Paclitaxel Albumin-Stabilized Nanoparticle Formulation With or Without Trastuzumab in Treating Patients With Breast Cancer Previously Treated With Surgery
NCT00602043	PHASE2	COMPLETED	F-18 16 Alpha-Fluoroestradiol-Labeled Positron Emission Tomography in Predicting Response to First-Line Hormone Therapy in Patients With Stage IV Breast Cancer
NCT00676663	PHASE2	COMPLETED	Study to Evaluate Exemestane With and Without Entinostat (SNDX-275) in Treatment of Postmenopausal Women With Advanced Breast Cancer
NCT00828854	PHASE2	COMPLETED	Study of the Effect of the Addition of SNDX-275 (Entinostat) to Continued Aromatase Inhibitor (AI) Therapy in Postmenopausal Women With ER+ Breast Cancer Whose Disease is Progressing
NCT00952731	PHASE2	COMPLETED	4-Hydroxytamoxifen or Tamoxifen Citrate in Treating Women With Newly Diagnosed Ductal Breast Carcinoma in Situ
NCT01037790	PHASE2	COMPLETED	Phase II Trial of the Cyclin-Dependent Kinase Inhibitor PD 0332991 in Patients With Cancer
NCT01100489	PHASE2	WITHDRAWN	Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer
NCT01194440	PHASE2	COMPLETED	Zoledronic Acid in Aromatase Inhibitor Induced Musculoskeletal Symptoms

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
TAMOXIFEN	4	15
EVEROLIMUS	4	5
EXEMESTANE	4	4
FULVESTRANT	4	4
ANASTROZOLE	4	3
ELACESTRANT	4	3
PALBOCICLIB	4	3
CAPIVASERTIB	4	2
TRIPTORELIN	4	2
VINORELBINE TARTRATE	4	2
ALDESLEUKIN	4	1
ALPELISIB	4	1
BUSULFAN	4	1
COBIMETINIB	4	1
ENTRECTINIB	4	1
FLUDEOXYGLUCOSE F 18	4	1
FLUOROESTRADIOL F-18	4	1
FUROSEMIDE	4	1
FUTIBATINIB	4	1
GEFITINIB	4	1
GOSERELIN ACETATE	4	1
HYALURONIDASE (HUMAN RECOMBINANT)	4	1
MEGESTROL ACETATE	4	1
PAZOPANIB HYDROCHLORIDE	4	1
PERTUZUMAB	4	1
PRASTERONE	4	1
RIBOCICLIB	4	1
SARGRAMOSTIM	4	1
THIOTEPA	4	1
TRASTUZUMAB DERUXTECAN	4	1

Precision-medicine subtype map (CIViC)

Drug × molecular subtype: 30 predictive associations from 31 curated evidence items.

Molecular subtype	Therapy	Effect	Level	CIViC
ESR1 D538G	Elacestrant	Sensitivity/Response	CIViC A	EID12219
ESR1 E380Q	Elacestrant	Sensitivity/Response	CIViC A	EID12224
ESR1 L469V	Elacestrant	Sensitivity/Response	CIViC A	EID12225
ESR1 L536H	Elacestrant	Sensitivity/Response	CIViC A	EID12226
ESR1 L536P	Elacestrant	Sensitivity/Response	CIViC A	EID12227
ESR1 L536Q	Elacestrant	Sensitivity/Response	CIViC A	EID12229
ESR1 L536R	Elacestrant	Sensitivity/Response	CIViC A	EID12228
ESR1 S463P	Elacestrant	Sensitivity/Response	CIViC A	EID12230
ESR1 Y537C	Elacestrant	Sensitivity/Response	CIViC A	EID12222
ESR1 Y537D	Elacestrant	Sensitivity/Response	CIViC A	EID12223
ESR1 Y537N	Elacestrant	Sensitivity/Response	CIViC A	EID12221
ESR1 Y537S	Elacestrant	Sensitivity/Response	CIViC A	EID12220
ESR1 Expression	Everolimus/Exemestane Regimen	Sensitivity/Response	CIViC B	EID12907 +1
FGFR1 Amplification	Fulvestrant + Lucitanib	Sensitivity/Response	CIViC B	EID12751
FOXA1 Mutation	Aromatase Inhibitor	Sensitivity/Response	CIViC B	EID12910
PIK3CA Mutation	Tamoxifen	Sensitivity/Response	CIViC B	EID6189
CCND1 Overexpression	Tamoxifen	Resistance	CIViC B	EID856
CDK6 Overexpression	Fulvestrant	Resistance	CIViC B	EID1526
PIK3CA P447_L455del	Letrozole + Alpelisib	Sensitivity/Response	CIViC C	EID9575
CDK4 EXPRESSION	Alpelisib	Sensitivity/Response	CIViC D	EID264
CDK6 Overexpression	Fulvestrant + Palbociclib	Sensitivity/Response	CIViC D	EID1527
FGFR1 Amplification	Ponatinib	Sensitivity/Response	CIViC D	EID1767
KDM5C Loss-of-function AND ( PIK3CA E545K OR PIK3CA H1047R OR PTEN Loss )	Capivasertib	Sensitivity/Response	CIViC D	EID12936
AURKA EXPRESSION	Tamoxifen	Resistance	CIViC D	EID1959
CCNE1 Amplification	Palbociclib	Resistance	CIViC D	EID1629
CDK6 Amplification	Abemaciclib	Resistance	CIViC D	EID4843
ESR1 S463P	Aromatase Inhibitor	Resistance	CIViC D	EID1727
FGFR1 Amplification OR FGFR1 Overexpression	Antiestrogen Therapy + CDK4/6 Inhibition	Resistance	CIViC D	EID12557
MMP1 Overexpression	Sacituzumab Govitecan	Resistance	CIViC D	EID12597
RB1 M695FS*26	Palbociclib	Resistance	CIViC D	EID1630

Cohort genes: AURKA, CCND1, CCNE1, CDK4, CDK6, ESR1, FGFR1, MMP1, PIK3CA, RB1, FGFR2, PDLIM2, RHOBTB2, ZNF613, CASC16
Drugs: Tamoxifen, Everolimus, Exemestane, Fulvestrant, Anastrozole, Elacestrant, Palbociclib, Capivasertib, Triptorelin, Vinorelbine Tartrate, Aldesleukin, Alpelisib, Busulfan, Cobimetinib, Entrectinib, FLUDEOXYGLUCOSE F 18, FLUOROESTRADIOL F-18, Furosemide, Futibatinib, Gefitinib, Goserelin Acetate, Hyaluronidase (Human Recombinant), Megestrol Acetate, Pazopanib, Pertuzumab, Prasterone, Ribociclib, Sargramostim, Thiotepa, Trastuzumab Deruxtecan, Ponatinib, Abemaciclib, Sacituzumab Govitecan