Progesterone-receptor negative breast cancer

Summary

Progesterone-receptor negative breast cancer (MONDO:0000616) is a cancer with 1 cohort gene (1 GWAS associations across 3 studies; 1 CIViC-evidence somatic driver) and 20 clinical trials. Top therapeutic interventions include carboplatin, aldesleukin, and busulfan.

At a glance

• Classification: Cancer
• Cohort genes: 1
• GWAS associations: 1
• Clinical trials: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	progesterone-receptor negative breast cancer
Mondo ID	MONDO:0000616
DOID	DOID:0060078
Is cancer (heuristic)	yes

Data availability: 1 GWAS association (3 studies).

Disease family

An umbrella term covering 1 Mondo subtype.

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 › progesterone-receptor negative breast cancer

Related subtypes (7): progesterone-receptor positive breast cancer, Her2-receptor negative breast cancer, breast tumor luminal A or B, HER2 positive breast carcinoma, normal breast-like subtype of breast carcinoma, estrogen-receptor positive breast cancer, estrogen-receptor negative breast cancer

Subtypes (1): triple-negative breast carcinoma

Genetics & variants

GWAS landscape

1 GWAS associations across 3 studies. Top hits map to 1 distinct genes (as reported by GWAS).

Top associations by p-value

rsID	p-value	Gene	Risk allele	Odds ratio
rs2981579	5e-07	FGFR2	T	1.23

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST007420	Lacson JCA	2017	1,049	1,310	Genome-Wide Testing of Exonic Variants and Breast Cancer Risk in the California Teachers Study.
GCST007417	Lacson JCA	2017	419	1,310	Genome-Wide Testing of Exonic Variants and Breast Cancer Risk in the California Teachers Study.
GCST90029051	Morra A	2021	0	0	Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

Tier	Variants
Tier 1: coding	0
Tier 2: splice/UTR	0
Tier 3: regulatory	0
Tier 4: intronic/intergenic	1

MAF distribution

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

Functional consequences

Consequence	Count
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs2981579	10	121577821	A>C,G,T	0.05	intron_variant	FGFR2	5e-07	Tier 4: intronic/intergenic

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 12 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
FGFR2	Act	BRCA,CHOL,LUSC,SACA,UCEC	CIViC #22

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
FGFR2	Orphanet:1540	Jackson-Weiss syndrome
FGFR2	Orphanet:1555	Cutis gyrata-acanthosis nigricans-craniosynostosis syndrome
FGFR2	Orphanet:168624	Familial scaphocephaly syndrome, McGillivray type
FGFR2	Orphanet:207	Crouzon syndrome
FGFR2	Orphanet:2363	Lacrimoauriculodentodigital syndrome
FGFR2	Orphanet:313855	FGFR2-related bent bone dysplasia
FGFR2	Orphanet:596008	Antley-Bixler syndrome without genital anomaly or disorder of steroidogenesis
FGFR2	Orphanet:794	Saethre-Chotzen syndrome
FGFR2	Orphanet:87	Apert syndrome
FGFR2	Orphanet:93258	Pfeiffer syndrome type 1
FGFR2	Orphanet:93259	Pfeiffer syndrome type 2
FGFR2	Orphanet:93260	Pfeiffer syndrome type 3

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
FGFR2	HGNC:3689	ENSG00000066468	P21802	Fibroblast growth factor receptor 2	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
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: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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	1	27.7×	0.036

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
FGFR2	Kinase	yes	2.7.10.1	Prot_kinase_dom, Ser-Thr/Tyr_kinase_cat_dom, Ig_sub2

Expression context

Cohort genes with no expression data: 0.

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

Breadth distribution (Bgee present_calls)

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

Top tissues across cohort

Tissue	Cohort genes
C1 segment of cervical spinal cord	1
corpus callosum	1
spinal cord	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
FGFR2	272	broad	marker	C1 segment of cervical spinal cord, spinal cord, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
FGFR2	449

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
FGFR2	P21802	63

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 18. Enrichment computed across 1 evidence-associated genes (1 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 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Signaling by FGFR2 amplification mutants	1	11420.0×	8e-04	FGFR2
Signaling by FGFR2 fusions	1	11420.0×	8e-04	FGFR2
FGFR2b ligand binding and activation	1	1142.0×	0.004	FGFR2
FGFR2c ligand binding and activation	1	878.5×	0.004	FGFR2
Activated point mutants of FGFR2	1	671.8×	0.004	FGFR2
Phospholipase C-mediated cascade; FGFR2	1	634.4×	0.004	FGFR2
Signaling by FGFR2 IIIa TM	1	601.0×	0.004	FGFR2
PI-3K cascade:FGFR2	1	496.5×	0.004	FGFR2
SHC-mediated cascade:FGFR2	1	475.8×	0.004	FGFR2
FRS-mediated FGFR2 signaling	1	439.2×	0.004	FGFR2
FGFR2 alternative splicing	1	423.0×	0.004	FGFR2
Negative regulation of FGFR2 signaling	1	368.4×	0.004	FGFR2
PI3K Cascade	1	271.9×	0.005	FGFR2
Signaling by FGFR2 in disease	1	265.6×	0.005	FGFR2
Constitutive Signaling by Aberrant PI3K in Cancer	1	126.9×	0.009	FGFR2
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	1	96.8×	0.012	FGFR2
PIP3 activates AKT signaling	1	66.8×	0.016	FGFR2
RAF/MAP kinase cascade	1	61.1×	0.016	FGFR2

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
fibroblast growth factor receptor signaling pathway involved in negative regulation of apoptotic process in bone marrow cell	1	16852.0×	0.001	FGFR2
fibroblast growth factor receptor signaling pathway involved in hemopoiesis	1	16852.0×	0.001	FGFR2
fibroblast growth factor receptor signaling pathway involved in positive regulation of cell proliferation in bone marrow	1	16852.0×	0.001	FGFR2
lateral sprouting from an epithelium	1	16852.0×	0.001	FGFR2
orbitofrontal cortex development	1	8426.0×	0.001	FGFR2
prostate gland morphogenesis	1	8426.0×	0.001	FGFR2
squamous basal epithelial stem cell differentiation involved in prostate gland acinus development	1	8426.0×	0.001	FGFR2
mammary gland bud formation	1	8426.0×	0.001	FGFR2
branch elongation involved in salivary gland morphogenesis	1	8426.0×	0.001	FGFR2
mesenchymal cell differentiation involved in lung development	1	8426.0×	0.001	FGFR2
regulation of osteoblast proliferation	1	5617.3×	0.001	FGFR2
fibroblast growth factor receptor signaling pathway involved in orbitofrontal cortex development	1	5617.3×	0.001	FGFR2
prostate epithelial cord elongation	1	5617.3×	0.001	FGFR2
ventricular zone neuroblast division	1	4213.0×	0.001	FGFR2
embryonic organ morphogenesis	1	4213.0×	0.001	FGFR2
reproductive structure development	1	4213.0×	0.001	FGFR2
regulation of morphogenesis of a branching structure	1	4213.0×	0.001	FGFR2
positive regulation of phospholipase activity	1	3370.4×	0.001	FGFR2
regulation of smooth muscle cell differentiation	1	3370.4×	0.001	FGFR2
branching involved in prostate gland morphogenesis	1	3370.4×	0.001	FGFR2
epithelial cell proliferation involved in salivary gland morphogenesis	1	3370.4×	0.001	FGFR2
mesenchymal cell proliferation involved in lung development	1	3370.4×	0.001	FGFR2
epidermis morphogenesis	1	2808.7×	0.001	FGFR2
gland morphogenesis	1	2407.4×	0.001	FGFR2
branching morphogenesis of a nerve	1	2407.4×	0.001	FGFR2
bud elongation involved in lung branching	1	2407.4×	0.001	FGFR2
positive regulation of epithelial cell proliferation involved in lung morphogenesis	1	2407.4×	0.001	FGFR2
prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis	1	2407.4×	0.001	FGFR2
pyramidal neuron development	1	2106.5×	0.001	FGFR2
otic vesicle formation	1	2106.5×	0.001	FGFR2

Therapeutics

Drug target analysis

Approved (phase 4): 1 · Phase ≥3: 1 · Phased (≥1): 1 · Undrugged: 0

Druggability breadth: 1 of 1 evidence-associated genes (100%) 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
FGFR2	PONATINIB

Top cohort targets by molecule count

Symbol	Molecules	Max phase
FGFR2	59	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
PONATINIB	4	FGFR2
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2
FEDRATINIB	4	FGFR2
LENVATINIB	4	FGFR2
AXITINIB	4	FGFR2
SORAFENIB	4	FGFR2
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2
NINTEDANIB ESYLATE	4	FGFR2
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2
SUNITINIB	4	FGFR2
DASATINIB	4	FGFR2
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2
LINIFANIB	3	FGFR2
SEMAXANIB	3	FGFR2
BRIVANIB	3	FGFR2
CEDIRANIB	3	FGFR2
DOVITINIB	3	FGFR2
LESTAURTINIB	3	FGFR2
TANDUTINIB	2	FGFR2
DORAMAPIMOD	2	FGFR2
FORETINIB	2	FGFR2

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
FGFR2	966	Binding:940, Functional:22, ADMET:4

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
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
FGFR2	966

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

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

Drug repurposing candidates

30 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)
PONATINIB	4	FGFR2
PEMIGATINIB	4	FGFR2
NINTEDANIB	4	FGFR2
FEDRATINIB	4	FGFR2
LENVATINIB	4	FGFR2
AXITINIB	4	FGFR2
SORAFENIB	4	FGFR2
INFIGRATINIB PHOSPHATE	4	FGFR2
INFIGRATINIB	4	FGFR2
IBRUTINIB	4	FGFR2
CERITINIB	4	FGFR2
VANDETANIB	4	FGFR2
NINTEDANIB ESYLATE	4	FGFR2
BRIGATINIB	4	FGFR2
ERDAFITINIB	4	FGFR2
FUTIBATINIB	4	FGFR2
PAZOPANIB	4	FGFR2
SUNITINIB	4	FGFR2
DASATINIB	4	FGFR2
ERLOTINIB	4	FGFR2
MIDOSTAURIN	4	FGFR2
LINIFANIB	3	FGFR2
SEMAXANIB	3	FGFR2
BRIVANIB	3	FGFR2
CEDIRANIB	3	FGFR2
DOVITINIB	3	FGFR2
LESTAURTINIB	3	FGFR2
TANDUTINIB	2	FGFR2
DORAMAPIMOD	2	FGFR2
FORETINIB	2	FGFR2

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	FGFR2
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

Undrugged target profiles

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

Clinical trials & evidence

Clinical trials

Clinical trials: 20.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	15
PHASE1	3
PHASE3	1
PHASE2/PHASE3	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01805076	PHASE3	COMPLETED	MRI and Mammography Before Surgery in Patients With Stage I-II Breast Cancer
NCT01881230	PHASE2/PHASE3	COMPLETED	Evaluate Risk/Benefit of Nab Paclitaxel in Combination With Gemcitabine and Carboplatin Compared to Gemcitabine and Carboplatin in Triple Negative Metastatic Breast Cancer (or Metastatic Triple Negative Breast Cancer)
NCT02315196	PHASE2	ACTIVE_NOT_RECRUITING	Pegylated Liposomal Doxorubicin Hydrochloride and Carboplatin Followed by Surgery and Paclitaxel in Treating Patients With Triple Negative Stage II-III 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
NCT00194779	PHASE2	COMPLETED	Combination Chemotherapy and Filgrastim Before Surgery in Treating Patients With HER2-Positive Breast Cancer That Can Be Removed By Surgery
NCT00559507	PHASE2	COMPLETED	Saracatinib in Treating Patients With Metastatic or Locally Advanced Breast Cancer That Cannot Be Removed By Surgery
NCT00577122	PHASE2	COMPLETED	Medroxyprogesterone +/- Cyclophosphamide & Methotrexate in Hormone Receptor-Negative Recurrent/Metastatic Breast Cancer
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
NCT00733408	PHASE2	COMPLETED	Nab-Paclitaxel and Bevacizumab Followed By Bevacizumab and Erlotinib in Metastatic Breast Cancer
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
NCT01151449	PHASE2	TERMINATED	Gamma-secretase/Notch Signalling Pathway Inhibitor RO4929097 in Treating Patients With Advanced, Metastatic, or Recurrent Triple Negative Invasive Breast Cancer
NCT01173497	PHASE2	COMPLETED	A Study Evaluating INIPARIB in Combination With Chemotherapy to Treat Triple Negative Breast Cancer Brain Metastasis
NCT01234532	PHASE2	TERMINATED	Entinostat and Anastrozole in Treating Postmenopausal Women With TNBC That Can Be Removed by Surgery
NCT01372579	PHASE2	UNKNOWN	Carboplatin and Eribulin Mesylate in Triple Negative Breast Cancer Patients
NCT01818063	PHASE2	COMPLETED	Carboplatin and Combination Chemotherapy With or Without Veliparib in Treating Patients With Stage IIB-IIIC Breast Cancer
NCT04504916	PHASE2	TERMINATED	A Study of Zilovertamab Vedotin (MK-2140/VLS-101) in Participants With Solid Tumors (MK-2140-002)
NCT00031681	PHASE1	COMPLETED	7-Hydroxystaurosporine and Irinotecan Hydrochloride in Treating Patients With Metastatic or Unresectable Solid Tumors or Triple Negative Breast Cancer (Currently Accruing Only Triple-negative Breast Cancer Patients Since 6/8/2007)
NCT00516243	PHASE1	COMPLETED	Defined Green Tea Catechin Extract in Treating Women With Hormone Receptor Negative Stage I-III Breast Cancer
NCT01104259	PHASE1	COMPLETED	Veliparib, Cisplatin, and Vinorelbine Ditartrate in Treating Patients With Recurrent and/or Metastatic Breast Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
CARBOPLATIN	4	4
ALDESLEUKIN	4	1
BUSULFAN	4	1
EPIRUBICIN HYDROCHLORIDE	4	1
ERIBULIN MESYLATE	4	1
FLUDEOXYGLUCOSE F 18	4	1
FLUOROESTRADIOL F-18	4	1
PALBOCICLIB	4	1
SARGRAMOSTIM	4	1
THIOTEPA	4	1
VINORELBINE TARTRATE	4	1
VELIPARIB	3	4
CIRMTUZUMAB	3	1
ENTINOSTAT	3	1
INIPARIB	3	1
SARACATINIB	3	1
UCN-01	2	1
VEDOTIN	2	1
CHEMBL4438584	0	1
CHEMBL1236539	0	1