Breast lobular carcinoma

Summary

Breast lobular carcinoma (MONDO:0000552) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record) and 20 clinical trials. Top therapeutic interventions include fluciclovine f18, gallium ga 68 gozetotide, and naltrexone.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 20

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	breast lobular carcinoma
Mondo ID	MONDO:0000552
EFO	EFO:0008509
DOID	DOID:0050938
NCIT	C3771
SNOMED CT	278054005
UMLS	C0206692
MedGen	64634
Anatomy (UBERON)	UBERON:0001912
Is cancer (heuristic)	yes

Also known as: carcinoma of lobule of mammary gland · lobular adenocarcinoma · lobular breast carcinoma · lobular carcinoma · lobular carcinoma of breast · lobular carcinoma of the breast · lobule of mammary gland carcinoma

Data availability: 1 ClinVar variant · 2 cell lines.

Disease family

An umbrella term covering 2 Mondo subtypes.

Classification path: disease › human disease › disease by body system or component › integumentary system disorder › integumentary system cancer › breast adenocarcinoma › breast lobular carcinoma

Related subtypes (12): mammary Paget disease, signet ring cell breast carcinoma, breast mucinous cystadenocarcinoma, mucoepidermoid breast carcinoma, adenoid cystic breast carcinoma, sebaceous breast carcinoma, oncocytic breast carcinoma, breast malignant eccrine spiradenoma, breast ductal adenocarcinoma, lobular breast carcinoma in situ, mixed lobular and ductal breast carcinoma, inflammatory breast carcinoma

Subtypes (2): invasive lobular breast carcinoma, CTNNA1-related diffuse gastric and lobular breast cancer syndrome

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
12234	NM_004360.5(CDH1):c.781G>T (p.Glu261Ter)	CDH1	Pathogenic	reviewed by expert panel

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 5 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
CDH1	LoF	BLCA,BRCA,CSCC,DLBCLNOS,ESCA,STAD	CIViC #888

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
CDH1	Orphanet:1331	Familial prostate cancer
CDH1	Orphanet:199306	Cleft lip/palate
CDH1	Orphanet:1997	Blepharo-cheilo-odontic syndrome
CDH1	Orphanet:227535	Hereditary breast cancer
CDH1	Orphanet:26106	Hereditary diffuse gastric cancer

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
CDH1	HGNC:1748	ENSG00000039068	P12830	Cadherin-1	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
CDH1	Cadherin-1	Cadherins are calcium-dependent cell adhesion proteins.

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

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
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
CDH1	Other/Unknown	no		Cadherin_Y-type_LIR, Cadherin-like_dom, Cadherin_pro_dom

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
esophagus squamous epithelium	1
gingival epithelium	1
jejunal mucosa	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
CDH1	245	broad	marker	jejunal mucosa, esophagus squamous epithelium, gingival epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
CDH1	8,738

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
CDH1	P12830	22

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 44. 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
Epithelial-Mesenchymal Transition (EMT) during gastrulation	1	1427.5×	0.006	CDH1
InlA-mediated entry of Listeria monocytogenes into host cells	1	1268.9×	0.006	CDH1
Apoptotic cleavage of cell adhesion proteins	1	1038.2×	0.006	CDH1
Listeria monocytogenes entry into host cells	1	1038.2×	0.006	CDH1
Regulation of CDH1 mRNA translation by microRNAs	1	1038.2×	0.006	CDH1
Regulation of CDH1 Function	1	951.7×	0.006	CDH1
Positive Regulation of CDH1 Gene Transcription	1	951.7×	0.006	CDH1
Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition	1	878.5×	0.006	CDH1
Developmental Lineage of Mammary Stem Cells	1	761.3×	0.006	CDH1
Formation of definitive endoderm	1	713.8×	0.006	CDH1
Developmental Lineage of Mammary Gland Myoepithelial Cells	1	543.8×	0.006	CDH1
SRC activates STAT3 in a quantitative manner, through Cadherin-11 (CDH11), RAC1 and gp130 (IL6ST)	1	496.5×	0.006	CDH1
Apoptotic cleavage of cellular proteins	1	475.8×	0.006	CDH1
Apoptotic execution phase	1	475.8×	0.006	CDH1
Developmental Lineage of Mammary Gland Luminal Epithelial Cells	1	456.8×	0.006	CDH1
RHO GTPases activate IQGAPs	1	346.1×	0.007	CDH1
Regulation of CDH1 posttranslational processing and trafficking to plasma membrane	1	335.9×	0.007	CDH1
Bacterial Infection Pathways	1	335.9×	0.007	CDH1
Gastrulation	1	259.6×	0.008	CDH1
Adherens junctions interactions	1	248.3×	0.008	CDH1
Cell-cell junction organization	1	248.3×	0.008	CDH1
Degradation of CDH1	1	196.9×	0.010	CDH1
Cell junction organization	1	187.2×	0.010	CDH1
MITF-M-dependent gene expression	1	181.3×	0.010	CDH1
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.010	CDH1
Apoptosis	1	167.9×	0.010	CDH1
Activation of STAT3 by cadherin engagement	1	163.1×	0.010	CDH1
Programmed Cell Death	1	146.4×	0.011	CDH1
Cell-Cell communication	1	137.6×	0.011	CDH1
Integrin cell surface interactions	1	134.3×	0.011	CDH1

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
response to heparin	1	5617.3×	0.002	CDH1
regulation of protein catabolic process at postsynapse, modulating synaptic transmission	1	4213.0×	0.002	CDH1
cellular response to indole-3-methanol	1	3370.4×	0.002	CDH1
response to Gram-positive bacterium	1	2808.7×	0.002	CDH1
desmosome assembly	1	2407.4×	0.002	CDH1
positive regulation of protein localization	1	1404.3×	0.003	CDH1
cellular response to lithium ion	1	1123.5×	0.003	CDH1
negative regulation of cell-cell adhesion	1	991.3×	0.003	CDH1
negative regulation of axon extension	1	732.7×	0.004	CDH1
pituitary gland development	1	648.1×	0.004	CDH1
adherens junction organization	1	510.7×	0.004	CDH1
calcium-dependent cell-cell adhesion	1	481.5×	0.004	CDH1
cell-cell junction assembly	1	443.5×	0.004	CDH1
positive regulation of protein import into nucleus	1	421.3×	0.004	CDH1
cell-cell adhesion mediated by cadherin	1	411.0×	0.004	CDH1
synapse assembly	1	230.8×	0.007	CDH1
response to toxic substance	1	210.7×	0.008	CDH1
cell morphogenesis	1	157.5×	0.010	CDH1
homophilic cell-cell adhesion	1	140.4×	0.010	CDH1
neuron projection development	1	122.1×	0.011	CDH1
negative regulation of cell migration	1	111.6×	0.011	CDH1
protein localization to plasma membrane	1	108.7×	0.011	CDH1
cell-cell adhesion	1	101.5×	0.012	CDH1
regulation of gene expression	1	83.4×	0.013	CDH1
response to xenobiotic stimulus	1	69.1×	0.016	CDH1
cell migration	1	61.5×	0.017	CDH1
positive regulation of DNA-templated transcription	1	27.9×	0.036	CDH1

Therapeutics

Drugs indicated for this disease

No approved or late-stage (phase ≥3) drug is indicated for this disease; the following are in earlier-phase trials only.

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Doconexent, Icosapent, Letrozole.

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
CDH1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

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

Symbol	Assays	Type breakdown
CDH1	18	Binding:18

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

0 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.

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
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	1	CDH1

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
CDH1	18	—

Clinical trials & evidence

Clinical trials

Clinical trials: 20.

Phase distribution (across all retrieved trials)

Phase	Trials
Not specified	13
PHASE2	3
PHASE1	2
PHASE3	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT06067503	PHASE2	RECRUITING	Biomarkers to Detect Endocrine Therapy Resistance
NCT02137252	PHASE2	TERMINATED	Naltrexone RCT for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer
NCT03620643	PHASE2	COMPLETED	Crizotinib in Lobular Breast, Diffuse Gastric and Triple Negative Lobular Breast Cancer or CDH1-mutated Solid Tumours
NCT07020806	PHASE1	RECRUITING	[68Ga]Ga DOTA-5G as a Diagnostic Imaging Agent for Metastatic/Advanced Invasive Lobular Breast Cancer (LBC)
NCT04750473	PHASE1	COMPLETED	Fluciclovine and PSMA PET/CT for the Classification and Improved Staging of Invasive Lobular Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT05410951	Not specified	ACTIVE_NOT_RECRUITING	LobularCard Trial: Searching for Novel Germline Mutations in Lobular Breast Cancer Patients
NCT05463796	Not specified	RECRUITING	InAdvance: Surveillance, Prevention, and Interception in a Population at Risk for Cancer
NCT05837767	Not specified	RECRUITING	A Study of Radiation Therapy to Treat Solid Tumor Cancer That Has Spread to Soft Tissue
NCT05931302	Not specified	ACTIVE_NOT_RECRUITING	Initial Staging of Lobular Breast Carcinoma: Head to Head Comparison of 68Ga-FAPI-46 and 18F-FDG PET/CT
NCT05964504	Not specified	RECRUITING	Improving Survival for Metastatic Lobular Breast Cancer (PLUMB Registry)
NCT05982496	Not specified	NOT_YET_RECRUITING	18F FES-PET/MRI for Tailoring Treatment of Luminal a and Lobular Breast Cancer
NCT06557148	Not specified	RECRUITING	A Study Comparing Cancer Imaging Approaches in People With Lobular Breast Cancer
NCT07313033	Not specified	NOT_YET_RECRUITING	[68]GA-FAPI-46 PET/CT for the Diagnosis of Metastatic Lesions in Patients With Lobular Breast Cancer (ICL).
NCT07613151	Not specified	RECRUITING	Negative Hormone Receptor and APOcrine Lobular Invasive Breast Cancer
NCT00581750	Not specified	COMPLETED	Molecular Genetic Basis of Invasive Breast Cancer Risk Associated With Lobular Carcinoma in Situ
NCT01038258	Not specified	UNKNOWN	Monitoring Response After The First Chemotherapy Cycle After Neoadjuvant Breast Cancer Therapy
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery
NCT04206891	Not specified	COMPLETED	CDH1 Germline Mutations in Lobular Breast Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FLUCICLOVINE F18	4	1
GALLIUM GA 68 GOZETOTIDE	4	1
NALTREXONE	4	1