Invasive lobular breast carcinoma

Summary

Invasive lobular breast carcinoma (MONDO:0005051) is a cancer with 3 cohort genes (2 GWAS associations across 1 studies; 2 CIViC-evidence somatic drivers; 1 ClinVar predisposition record) and 19 clinical trials. Top therapeutic interventions include fulvestrant, indocyanine green acid form, and anastrozole.

At a glance

• Classification: Cancer
• Cohort genes: 3
• GWAS associations: 2
• ClinVar variants: 1
• Clinical trials: 19

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	invasive lobular breast carcinoma
Mondo ID	MONDO:0005051
EFO	EFO:0000553
DOID	DOID:3457
NCIT	C7950
UMLS	C0279565
MedGen	75994
Is cancer (heuristic)	yes

Also known as: breast invasive lobular carcinoma · classic invasive lobular carcinoma · infiltrating lobular adenocarcinoma · infiltrating lobular breast carcinoma · infiltrating lobular carcinoma of breast · infiltrating lobular carcinoma of the breast · invasive lobular adenocarcinoma · invasive lobular breast carcinoma · invasive lobular carcinoma · invasive lobular carcinoma of breast · invasive lobular carcinoma of the breast · invasive lobular carcinoma, classic type · lobular carcinoma · lobular carcinoma (morphologic abnormality) · lobular carcinoma NOS (morphologic abnormality) · lobular carcinoma of the breast

Data availability: 1 ClinVar variant · 2 GWAS associations (1 study).

Disease family

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

Related subtypes (1): CTNNA1-related diffuse gastric and lobular breast cancer syndrome

Genetics & variants

GWAS landscape

2 GWAS associations across 1 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
rs11654964	3e-06	TMEM132E - CCT6B	?	1.67
rs7648642	5e-06	CD80	?	1.56

Top studies (by case count)

Study	Lead author	Year	Cases	Controls	Title
GCST002266	Rudolph A	2013	541	0	Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study.

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	2

MAF distribution

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

Functional consequences

Consequence	Count
intergenic_variant	1
intron_variant	1

Top variants

rsID	Chr	Pos	Alleles	MAF	Consequence	Gene	p-value	Tier
rs11654964	17	34662519	A>C,T	0.05	intergenic_variant	TMEM132E - CCT6B	3e-06	Tier 4: intronic/intergenic
rs7648642	3	119542528	A>C	0.05	intron_variant	CD80	5e-06	Tier 4: intronic/intergenic

ClinVar germline variants

1 retrieved; paginated sample, class counts are floors:

1 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
37898	NM_000059.4(BRCA2):c.4376A>G (p.Asn1459Ser)	BRCA2	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 13 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
BRCA2	LoF	BLCA,BRCA,CESC,CHOL,HCC,HNSC,LUSC,MBL,OVT,PAAD,PRAD,PROSTATE,RCC,VULVA	CIViC #7
CD80			CIViC #836

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
BRCA2	Orphanet:1331	Familial prostate cancer
BRCA2	Orphanet:1333	Familial pancreatic carcinoma
BRCA2	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
BRCA2	Orphanet:178	Chordoma
BRCA2	Orphanet:227535	Hereditary breast cancer
BRCA2	Orphanet:319462	Inherited cancer-predisposing syndrome due to biallelic BRCA2 mutations
BRCA2	Orphanet:440437	Familial colorectal cancer Type X
BRCA2	Orphanet:654	Nephroblastoma
BRCA2	Orphanet:667662	Breast implant-associated anaplastic large cell lymphoma
BRCA2	Orphanet:694963	Inflammatory breast cancer
BRCA2	Orphanet:70567	Cholangiocarcinoma
BRCA2	Orphanet:84	Fanconi anemia
TMEM132E	Orphanet:90636	Rare autosomal recessive non-syndromic sensorineural deafness type DFNB

Cohort genes → proteins

3 cohort genes, 3 distinct canonical proteins.

Evidence partition

Subset	Genes
gwas_only	2
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
BRCA2	HGNC:1101	ENSG00000139618	P51587	Breast cancer type 2 susceptibility protein	clinvar
CD80	HGNC:1700	ENSG00000121594	P33681	T-lymphocyte activation antigen CD80	gwas
TMEM132E	HGNC:26991	ENSG00000181291	Q6IEE7	Transmembrane protein 132E	gwas

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
BRCA2	Breast cancer type 2 susceptibility protein	Involved in double-strand break repair and/or homologous recombination.
CD80	T-lymphocyte activation antigen CD80	Costimulatory molecule that belongs to the immunoglobulin superfamily that plays an important role in T-lymphocyte activation.
TMEM132E	Transmembrane protein 132E	Required for normal inner ear hair cell function and hearing.

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 2 · Druggable fraction: 0.33

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
Antibody/Immunoglobulin	1	9.7×	0.199
Other/Unknown	2	1.2×	0.587

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
BRCA2	Other/Unknown	no		BRCA2_repeat, NA-bd_OB-fold, BRCA2_OB_1
CD80	Antibody/Immunoglobulin	yes		Ig_sub, Ig-like_dom, Ig_V-set
TMEM132E	Other/Unknown	no		TMEM132, TMEM132_N, TMEM132_C

Expression context

Cohort genes with no expression data: 0.

2 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)	0
broad (>20)	3
unknown	0

Top tissues across cohort

Tissue	Cohort genes
male germ line stem cell (sensu Vertebrata) in testis	2
secondary oocyte	1
ventricular zone	1
lower lobe of lung	1
pancreatic ductal cell	1
cerebellar hemisphere	1
kidney epithelium	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
BRCA2	184	ubiquitous	marker	male germ line stem cell (sensu Vertebrata) in testis, secondary oocyte, ventricular zone
CD80	143	broad	marker	male germ line stem cell (sensu Vertebrata) in testis, lower lobe of lung, pancreatic ductal cell
TMEM132E	169	tissue_specific	yes	kidney epithelium, right hemisphere of cerebellum, cerebellar hemisphere

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
BRCA2	4,839
CD80	3,664
TMEM132E	653

Structural data

PDB: 2 · AlphaFold-only: 1 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
BRCA2	P51587	14
CD80	P33681	6

AlphaFold-only cohort genes (top 30 by pLDDT)

Symbol	UniProt	pLDDT
TMEM132E	Q6IEE7	72.44

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 45. Enrichment computed across 3 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Impaired BRCA2 translocation to the nucleus	1	1903.3×	0.012	BRCA2
Impaired BRCA2 binding to SEM1 (DSS1)	1	1903.3×	0.012	BRCA2
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	475.8×	0.012	BRCA2
CD28 dependent Vav1 pathway	1	439.2×	0.012	CD80
HDR through MMEJ (alt-NHEJ)	1	439.2×	0.012	BRCA2
Diseases of DNA Double-Strand Break Repair	1	407.9×	0.012	BRCA2
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	407.9×	0.012	BRCA2
Resolution of D-Loop Structures	1	317.2×	0.012	BRCA2
Diseases of DNA repair	1	285.5×	0.012	BRCA2
Co-inhibition by CTLA4	1	259.6×	0.012	CD80
Impaired BRCA2 binding to PALB2	1	228.4×	0.012	BRCA2
Regulation of T cell activation by CD28 family	1	211.5×	0.012	CD80
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	211.5×	0.012	BRCA2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	211.5×	0.012	BRCA2
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	211.5×	0.012	BRCA2
CD28 dependent PI3K/Akt signaling	1	196.9×	0.012	CD80
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	196.9×	0.012	BRCA2
Co-stimulation by CD28	1	190.3×	0.012	CD80
Homologous DNA Pairing and Strand Exchange	1	190.3×	0.012	BRCA2
PI3K/AKT Signaling in Cancer	1	184.2×	0.012	CD80
Homology Directed Repair	1	154.3×	0.012	BRCA2
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	154.3×	0.012	BRCA2
Impaired BRCA2 binding to RAD51	1	154.3×	0.012	BRCA2
Resolution of D-loop Structures through Holliday Junction Intermediates	1	150.3×	0.012	BRCA2
Meiosis	1	142.8×	0.012	BRCA2
Negative regulation of the PI3K/AKT network	1	139.3×	0.012	CD80
Presynaptic phase of homologous DNA pairing and strand exchange	1	135.9×	0.012	BRCA2
Disease	2	13.1×	0.012	BRCA2, CD80
DNA Double-Strand Break Repair	1	124.1×	0.012	BRCA2
Interleukin-10 signaling	1	116.5×	0.013	CD80

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
posterior lateral line neuromast hair cell development	1	5617.3×	0.008	TMEM132E
mitotic recombination-dependent replication fork processing	1	2808.7×	0.008	BRCA2
negative regulation of T cell mediated immunity	1	1872.4×	0.008	CD80
negative regulation of mammary gland epithelial cell proliferation	1	1123.5×	0.010	BRCA2
positive regulation of T-helper 1 cell differentiation	1	936.2×	0.010	CD80
establishment of protein localization to telomere	1	702.2×	0.010	BRCA2
response to UV-C	1	561.7×	0.010	BRCA2
telomere maintenance via recombination	1	510.7×	0.010	BRCA2
positive regulation of signal transduction	1	432.1×	0.010	CD80
regulation of DNA damage checkpoint	1	374.5×	0.010	BRCA2
inner cell mass cell proliferation	1	330.4×	0.010	BRCA2
positive regulation of granulocyte macrophage colony-stimulating factor production	1	330.4×	0.010	CD80
centrosome duplication	1	312.1×	0.010	BRCA2
response to X-ray	1	295.6×	0.010	BRCA2
female gonad development	1	267.5×	0.010	BRCA2
positive regulation of peptidyl-tyrosine phosphorylation	1	267.5×	0.010	CD80
positive regulation of T cell receptor signaling pathway	1	255.3×	0.010	CD80
positive regulation of DNA-templated transcription	2	18.6×	0.010	BRCA2, CD80
hematopoietic stem cell proliferation	1	216.1×	0.011	BRCA2
oocyte maturation	1	200.6×	0.011	BRCA2
male meiosis I	1	193.7×	0.011	BRCA2
response to gamma radiation	1	193.7×	0.011	BRCA2
negative regulation of T cell activation	1	175.5×	0.011	CD80
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	1	165.2×	0.011	BRCA2
positive regulation of interleukin-2 production	1	156.0×	0.011	CD80
positive regulation of mitotic cell cycle	1	156.0×	0.011	BRCA2
regulation of cytokinesis	1	140.4×	0.012	BRCA2
cellular response to ionizing radiation	1	137.0×	0.012	BRCA2
nucleotide-excision repair	1	127.7×	0.012	BRCA2
T cell costimulation	1	124.8×	0.012	CD80

Therapeutics

Drugs indicated for this disease

0 approved, 2 in late-stage (phase 3) trials. Disease-direct ChEMBL indications, not inferred from the associated-gene cohort below.

Drug	Development status
Anastrozole	Phase 3 (in late-stage trials)
Fulvestrant	Phase 3 (in late-stage trials)

Earlier-phase candidates (phase 2, investigational — efficacy not yet established): Entrectinib, Fluoroestradiol, Goserelin, Letrozole.

Drug target analysis

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

Druggability breadth: 1 of 3 evidence-associated genes (33%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
BRCA2	0	0
CD80	0	0
TMEM132E	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 3; 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	1	CD80
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	2	BRCA2, TMEM132E

Undrugged target profiles

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

Symbol	ChEMBL assays	Drugged partners (top 3)
BRCA2	0	—
CD80	0	—
TMEM132E	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 19.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	8
Not specified	8
PHASE3	1
PHASE1/PHASE2	1
EARLY_PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01953588	PHASE3	ACTIVE_NOT_RECRUITING	Fulvestrant and/or Anastrozole in Treating Postmenopausal Patients With Stage II-III Breast Cancer Undergoing Surgery
NCT07229417	PHASE2	RECRUITING	IvoLoC Trial: A Phase II Trial Evaluating the Efficacy of Ivonescimab in Metastatic Endocrine Refractory HR-positive HER2-negative or Triple Negative Invasive Lobular Carcinoma
NCT07432633	PHASE1/PHASE2	RECRUITING	[18F]FPyQCP PET Imaging of Fibroblast Activation Protein in Selected Oncology Indications
NCT01100489	PHASE2	WITHDRAWN	Breast-Conserving Surgery Followed by Radiation Therapy With MRI-Detected Stage I or Stage II Breast Cancer
NCT01417286	PHASE2	COMPLETED	Accelerated Radiation Therapy After Surgery in Treating Patients With Breast Cancer
NCT01641406	PHASE2	UNKNOWN	Phase II Study of PET Guided Neoadjuvant Chemotherapy (NAC) and Oncotype Guided Hormonal Therapy of Breast Cancer
NCT02137252	PHASE2	TERMINATED	Naltrexone RCT for Treatment-Emergent Fatigue in Patients Receiving Radiation Therapy for Breast Cancer
NCT04252859	PHASE2	TERMINATED	[18F]Fluoroestradiol-PET/CT Imaging of Invasive Lobular Carcinoma
NCT04551495	PHASE2	UNKNOWN	Neoadjuvant Study of Targeting ROS1 in Combination With Endocrine Therapy in Invasive Lobular Carcinoma of the Breast (ROSALINE)
NCT06408168	PHASE2	TERMINATED	Phase II Study of REPotrectinib With or Without Fulvestrant in Patients With Hormone Receptor-positive Human Epidermal Growth Factor 2-negative Metastatic Invasive LObular Carcinoma Who Received a Prior Endocrine Therapy in Combination With Cyclin-dependent Kinase 4 and 6 Inhibitor (REPLOT Trial)
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT05463796	Not specified	RECRUITING	InAdvance: Surveillance, Prevention, and Interception in a Population at Risk for 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).
NCT07527468	Not specified	NOT_YET_RECRUITING	HISMAR: Intraoperative Margin Assessment Using the Histolog® Scanner to Reduce Reoperation in Breast-Conserving Surgery
NCT00581750	Not specified	COMPLETED	Molecular Genetic Basis of Invasive Breast Cancer Risk Associated With Lobular Carcinoma in Situ
NCT01706432	Not specified	COMPLETED	Hypofractionated Image Guided Radiation Therapy in Treating Patients With Stage IV Breast Cancer
NCT01819233	Not specified	COMPLETED	Caloric Restriction in Treating Patients With Stage 0-I Breast Cancer Undergoing Surgery and Radiation Therapy
NCT04021069	Not specified	UNKNOWN	Using Clinicopathomic Markers to Predict Neoadjuvant Chemotherapy Response in Breast Cancer
NCT06133647	Not specified	COMPLETED	Demographics, Characteristics and Outcomes of Male Breast Cancer Patients at Methodist Health System

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
FULVESTRANT	4	2
INDOCYANINE GREEN ACID FORM	4	2
ANASTROZOLE	4	1
ENTRECTINIB	4	1
REPOTRECTINIB	4	1
IVONESCIMAB	3	1
CHEMBL5402818	0	1
CHEMBL5173501	0	1
CHEMBL5400169	0	1