Bilateral breast carcinoma

Summary

Bilateral breast carcinoma (MONDO:0003982) is a cancer with 1 cohort gene (1 CIViC-evidence somatic driver; 1 ClinVar predisposition record) and 4 clinical trials. Top therapeutic interventions include ixabepilone and berzosertib.

At a glance

• Classification: Cancer
• Cohort genes: 1
• ClinVar variants: 1
• Clinical trials: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	bilateral breast carcinoma
Mondo ID	MONDO:0003982
DOID	DOID:6741
NCIT	C8287
UMLS	C0281267
MedGen	128977
Is cancer (heuristic)	yes

Also known as: bilateral breast cancer · bilateral breast carcinoma

Data availability: 1 ClinVar variant.

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 › bilateral breast carcinoma

Related subtypes (12): nipple carcinoma, female breast carcinoma, sporadic breast cancer, breast carcinoma in situ, breast adenocarcinoma, male breast carcinoma, breast carcinoma by gene expression profile, invasive breast carcinoma, Ehrlich tumor carcinoma, hereditary breast carcinoma, cribriform carcinoma of breast, hormone-resistant breast carcinoma

Subtypes (2): synchronous bilateral breast carcinoma, lipid-rich breast carcinoma

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 conflicting classifications of pathogenicity

ClinVar	Variant (HGVS)	Gene	Classification	Review
141183	NM_000051.4(ATM):c.2021A>G (p.His674Arg)	ATM	Conflicting classifications of pathogenicity	criteria provided, conflicting classifications

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 0 · Orphanet: 8 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

Somatic driver evidence (intOGen + CIViC, cohort fanout)

Gene	intOGen role	Cancer types	CIViC
ATM	LoF	BLCA,BRCA,CCRCC,CHOL,CLLSLL,COAD,COADREAD,ESCA,HCC,LUAD,LUSC,MEL,NSCLC,PAAD,PANCREAS,PANET,PCM,PLMESO,PRAD,PROSTATE,STAD,UCEC,UTUC,WDTC	CIViC #69

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
ATM	Orphanet:100	Ataxia-telangiectasia
ATM	Orphanet:1331	Familial prostate cancer
ATM	Orphanet:145	Hereditary breast and/or ovarian cancer syndrome
ATM	Orphanet:227535	Hereditary breast cancer
ATM	Orphanet:370109	Ataxia-telangiectasia variant
ATM	Orphanet:440437	Familial colorectal cancer Type X
ATM	Orphanet:52416	Mantle cell lymphoma
ATM	Orphanet:67038	B-cell chronic lymphocytic leukemia

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
ATM	HGNC:795	ENSG00000149311	Q13315	Serine-protein kinase ATM	clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
ATM	Serine-protein kinase ATM	Serine/threonine protein kinase which activates checkpoint signaling upon double strand breaks (DSBs), apoptosis and genotoxic stresses such as ionizing ultraviolet A light (UVA), thereby acting as a DNA damage sensor.

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)
ATM	Kinase	yes	2.7.11.1	PI3/4_kinase_cat_dom, PIK-rel_kinase_FAT, FATC_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
calcaneal tendon	1
colonic epithelium	1
corpus callosum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
ATM	286	ubiquitous	marker	calcaneal tendon, colonic epithelium, corpus callosum

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
ATM	7,383

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
ATM	Q13315	14

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 61. 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
Sensing of DNA Double Strand Breaks	1	1903.3×	0.007	ATM
TP53 Regulates Transcription of Caspase Activators and Caspases	1	951.7×	0.007	ATM
Pexophagy	1	951.7×	0.007	ATM
Defective homologous recombination repair (HRR) due to PALB2 loss of function	1	951.7×	0.007	ATM
Diseases of DNA Double-Strand Break Repair	1	815.7×	0.007	ATM
Defective homologous recombination repair (HRR) due to BRCA2 loss of function	1	815.7×	0.007	ATM
Stabilization of p53	1	761.3×	0.007	ATM
p53-Dependent G1 DNA Damage Response	1	713.8×	0.007	ATM
p53-Dependent G1/S DNA damage checkpoint	1	713.8×	0.007	ATM
G1/S DNA Damage Checkpoints	1	671.8×	0.007	ATM
Resolution of D-Loop Structures	1	634.4×	0.007	ATM
Diseases of DNA repair	1	571.0×	0.007	ATM
TP53 Regulates Transcription of Cell Death Genes	1	543.8×	0.007	ATM
TP53 Regulates Transcription of Genes Involved in Cytochrome C Release	1	543.8×	0.007	ATM
Regulation of TP53 Activity through Methylation	1	543.8×	0.007	ATM
Regulation of TP53 Expression and Degradation	1	519.1×	0.007	ATM
DNA Double Strand Break Response	1	475.8×	0.007	ATM
Impaired BRCA2 binding to PALB2	1	456.8×	0.007	ATM
Defective homologous recombination repair (HRR) due to BRCA1 loss of function	1	423.0×	0.007	ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function	1	423.0×	0.007	ATM
Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function	1	423.0×	0.007	ATM
Cellular response to heat stress	1	393.8×	0.007	ATM
Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA)	1	393.8×	0.007	ATM
Homologous DNA Pairing and Strand Exchange	1	380.7×	0.007	ATM
Homology Directed Repair	1	308.6×	0.007	ATM
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)	1	308.6×	0.007	ATM
Impaired BRCA2 binding to RAD51	1	308.6×	0.007	ATM
Resolution of D-loop Structures through Holliday Junction Intermediates	1	300.5×	0.007	ATM
HDR through Single Strand Annealing (SSA)	1	292.8×	0.007	ATM
Regulation of TP53 Degradation	1	292.8×	0.007	ATM

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
establishment of RNA localization to telomere	1	8426.0×	0.002	ATM
establishment of protein-containing complex localization to telomere	1	8426.0×	0.002	ATM
positive regulation of telomerase catalytic core complex assembly	1	8426.0×	0.002	ATM
pre-B cell allelic exclusion	1	5617.3×	0.002	ATM
cellular response to nitrosative stress	1	5617.3×	0.002	ATM
peptidyl-serine autophosphorylation	1	3370.4×	0.003	ATM
negative regulation of telomere capping	1	3370.4×	0.003	ATM
regulation of telomere maintenance via telomerase	1	2808.7×	0.003	ATM
positive regulation of telomere maintenance via telomere lengthening	1	2808.7×	0.003	ATM
lipoprotein catabolic process	1	2407.4×	0.003	ATM
V(D)J recombination	1	2106.5×	0.003	ATM
meiotic telomere clustering	1	1872.4×	0.003	ATM
female meiotic nuclear division	1	1685.2×	0.003	ATM
histone mRNA catabolic process	1	1685.2×	0.003	ATM
cellular response to X-ray	1	1685.2×	0.003	ATM
DNA double-strand break processing	1	1532.0×	0.003	ATM
regulation of autophagosome assembly	1	1123.5×	0.003	ATM
pexophagy	1	1053.2×	0.003	ATM
regulation of cellular response to heat	1	1053.2×	0.003	ATM
positive regulation of DNA damage response, signal transduction by p53 class mediator	1	991.3×	0.003	ATM
replicative senescence	1	991.3×	0.003	ATM
negative regulation of B cell proliferation	1	936.2×	0.003	ATM
oocyte development	1	936.2×	0.003	ATM
cellular response to stress	1	842.6×	0.003	ATM
signal transduction in response to DNA damage	1	802.5×	0.003	ATM
positive regulation of telomere maintenance via telomerase	1	732.7×	0.004	ATM
cellular response to gamma radiation	1	601.9×	0.004	ATM
mitotic spindle assembly checkpoint signaling	1	561.7×	0.004	ATM
reciprocal meiotic recombination	1	561.7×	0.004	ATM
male meiotic nuclear division	1	543.6×	0.004	ATM

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
ATM	AMIODARONE HYDROCHLORIDE

Top cohort targets by molecule count

Symbol	Molecules	Max phase
ATM	35	4

Drugs targeting cohort genes (top 30)

Molecule	Max phase	Targets in cohort
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
DACTOLISIB	3	ATM
STREPTONIGRIN	2	ATM
CALCIMYCIN	2	ATM
ENPIROLINE	2	ATM
OXACEPROL	2	ATM
TOLONIUM CHLORIDE	2	ATM
ESTRADIOL BENZOATE	2	ATM
BERZOSERTIB	2	ATM
LARTESERTIB	2	ATM
ALTHIAZIDE	2	ATM

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
ATM	240	Binding:233, Functional:5, ADMET:2

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
ATM	2.7.11.1	non-specific serine/threonine protein kinase

Cohort genes with high screening signal

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

Symbol	ChEMBL assays
ATM	240

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

29 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)
AMIODARONE HYDROCHLORIDE	4	ATM
FURAZOLIDONE	4	ATM
ESTRADIOL ACETATE	4	ATM
NAFTIFINE HYDROCHLORIDE	4	ATM
METHYSERGIDE MALEATE	4	ATM
AMITRIPTYLINE HYDROCHLORIDE	4	ATM
XYLOMETAZOLINE HYDROCHLORIDE	4	ATM
FLUVOXAMINE MALEATE	4	ATM
ESTRADIOL VALERATE	4	ATM
PERMETHRIN	4	ATM
MITOTANE	4	ATM
TICLOPIDINE HYDROCHLORIDE	4	ATM
ENOXIMONE	4	ATM
METHYLENE BLUE ANHYDROUS	4	ATM
DITHIAZANINE IODIDE	4	ATM
ETHACRYNIC ACID	4	ATM
SECNIDAZOLE	4	ATM
MENADIONE	4	ATM
FENOFIBRATE	4	ATM
DIPYRIDAMOLE	4	ATM
DACTOLISIB	3	ATM
STREPTONIGRIN	2	ATM
CALCIMYCIN	2	ATM
ENPIROLINE	2	ATM
OXACEPROL	2	ATM
TOLONIUM CHLORIDE	2	ATM
ESTRADIOL BENZOATE	2	ATM
LARTESERTIB	2	ATM
ALTHIAZIDE	2	ATM

Druggability pyramid

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

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	1	ATM
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: 4.

Phase distribution (across all retrieved trials)

Phase	Trials
PHASE2	3
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT00877500	PHASE2	ACTIVE_NOT_RECRUITING	Ixabepilone in Treating Participants With Significant Residual Disease of HER2/Neu Negative Invasive Breast Cancer After Systemic Therapy
NCT03012100	PHASE2	ACTIVE_NOT_RECRUITING	Multi-epitope Folate Receptor Alpha Peptide Vaccine, GM-CSF, and Cyclophosphamide in Treating Patients With Triple Negative Breast Cancer
NCT05545150	PHASE2	ACTIVE_NOT_RECRUITING	Volumetric Specimen Imager Device for the Intraoperative Imaging of Patients With Breast Carcinoma and Breast Ductal Carcinoma In Situ, The VIVID Study
NCT04052555	PHASE1	ACTIVE_NOT_RECRUITING	Testing the Addition of an Anti-cancer Drug, Berzosertib, to the Usual Treatment (Radiation Therapy) for Chemotherapy-Resistant Triple-Negative and Estrogen and/or Progesterone Receptor Positive, HER2 Negative Breast Cancer

Drugs tested across these trials (top 30)

Molecule	Max phase	Trials referencing
IXABEPILONE	4	1
BERZOSERTIB	2	1