Breast Cancer: Recurrent Genomic Alterations: Difference between revisions

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'''Table 2 - Major clinically significant genes associated with somatic sequence alterations in breast cancer.''' Table derived from Geiersbach et al., 2018 [[https://pubmed.ncbi.nlm.nih.gov/32087595/ PMID 32087595]] with permission from Cancer Genetics.
'''Table 2 - Major clinically significant genes associated with somatic sequence alterations in breast cancer.'''  
{| class="wikitable"
{| class="wikitable"
|'''Gene(s)'''
|+
|'''CGC Evidence Level'''†
!
|'''Clinical Significance and Subgroup Association(s)'''
!
|'''Therapy Implication(s)'''
!
!
!
!
!
!
!
!
!
|-
|-
|''[[AKT1]]''
|
|2
|
|Metastatic BC
|
|AKT inhibitors
|
|
|
|
|
|
|
|
|-
|-
|''[[ATM]]''
|1
|Possible hereditary risk; TNBC
|PARP inhibitors (germline)
|-
|''[[BRCA1]], [[BRCA2]]''
|1
|Often hereditary risk; TNBC
|Platinum based therapy; PARP inhibitors (germline)
|-
|''[[CBFB]]''
|2
|ER-positive, Metastatic BC
|
|
|-
|
|''[[CCND1]], [[CCNE1]]''*
|
|2
|
|HER2-enriched
|
|CDK4/6 inhibitors
|
|-
|
|''[[CDK4]], [[CDK6]]''*
|
|2
|
|ER-positive, Metastatic BC
|
|CDK4/6 inhibitors
|-
|''[[CDH1]]''
|1
|Lobular histology; Possible hereditary risk
|
|
|-
|-
|''[[CDKN2A]]''
|2
|Metastatic BC
|
|
|-
|''[[CHEK2]]''
|1
|Often hereditary risk
|PARP inhibitors (germline)
|-
|''[[ERBB2]]''*
|1
|Rare activating sequence alterations; kinase domain  resistance mutations; HER2-enriched
|HER2-targeted therapy
|-
|''[[ESR1]]''
|1
|Metastatic ER-positive
|Hormone therapy resistance
|-
|''[[FGFR1]], [[FGFR2]], [[FGFR3]], [[FGFR4]]''
|2
|ER-positive
|FGFR inhibitors
|-
|''[[FOXA1]]''
|2
|ER-positive, Luminal subtype, lobular histology
|
|
|-
|''[[GATA3]]''
|2
|ER-positive, Luminal subtype
|
|
|-
|''[[JAK2]]''*
|2
|TNBC
|JAK2 inhibitors, immunotherapy
|-
|''[[MAP2K4]]''
|2
|Metastatic BC
|
|
|-
|''[[MAP3K1]]''
|2
|ER-positive, Metastatic BC
|
|
|-
|''[[MYC]]''*
|2
|
|
|
|
|-
|''[[NBN]]''
|1
|Possible hereditary risk
|PARP inhibitors (germline)
|-
|''[[NF1]]''
|1
|Possible hereditary risk
|mTOR/PI3K/AKT inhibitors (germline)
|-
|''[[NTRK1]], [[NTRK2]], [[NTRK3]]''
|1
|
|
|NTRK inhibitors
|-
|''[[PALB2]]''
|1
|Often hereditary risk
|PARP inhibitors (germline)
|-
|''[[PIK3CA]]''
|1
|ER-Positive, Luminal subtype
|PI3K inhibitors for selected hotspot mutations; acquired hormone resistance
|-
|''[[PTEN]]''
|2
|Loss in lobular BC
Possible hereditary risk
|mTOR/PI3K/AKT inhibitors; radiation contraindicated
|-
|''[[RB1]]''
|2
|Metastatic BC
|Acquired hormone resistance
|-
|''[[STK11]]''
|1
|Possible hereditary risk
|
|
|-
|''[[TBX3]]''
|2
|Lobular BC
|
|
|-
|''[[TOP2A]]''*
|2
|
|
|Anthracycline inhibitors
|-
|''[[TP53]]''
|1
|TNBC, HER2-enriched, Metastatic BC
Possible hereditary risk
|Radiation contraindicated
|}
|}
<nowiki>*</nowiki> Indicates genes more commonly activated by amplification than by sequence variation
Abbreviations: BC, breast cancer. TNBC, triple negative breast cancer.
Abbreviations: BC, breast cancer. TNBC, triple negative breast cancer.


Revision as of 15:00, 18 July 2025

Table 1 - Clinically significant copy number alterations and regions of loss of heterozygosity in breast cancer. Table derived from Geiersbach et al., 2018 [PMID 32087595] with permission from Cancer Genetics.[1]

Alteration Relevant Gene(s) CGC Evidence Level† Subgroup Association(s)
1q gain unknown 2 Most common copy number alteration, often with 16q loss; all subtypes
8p11.2 amplification FGFR1, ZNF703 2 METABRIC IntClust6, ER positive
8q24 amplification MYC 2 METABRIC IntClust9, ER positive
9p24 amplification JAK2, CD274, PDCD1LG2 2 Enriched in TNBC
10q23.3 loss or LOH PTEN 2 Enriched in TNBC and in lobular carcinoma
11q13-q14 gain / amplification CCND1, EMS1, and others 2 METABRIC IntClust2
16q loss / LOH CDH1 2 METABRIC IntClust2, ER positive
17p loss / LOH TP53 2 TNBC, basal-like intrinsic subtype
17q12 amplification ERBB2 (HER2) 1 METABRIC IntClust5, HER2-enriched
17q21 amplification TOP2A 2 METABRIC IntClust5, HER2-enriched
17q23 amplification (“17q distal amplicon”) RPS6KB, others 2 METABRIC IntClust1
19q12 CCNE1 2 METABRIC IntClust5; HER2-enriched
20q gain; 20q13 amp AURKA, GNAS, ZNF217 2 METABRIC IntClust1, ER Positive

† See table below Table 2 for CGC Evidence levels

Abbreviations: TNBC, triple negative breast cancer; LOH, loss of heterozygosity.


Table 2 - Major clinically significant genes associated with somatic sequence alterations in breast cancer.

Abbreviations: BC, breast cancer. TNBC, triple negative breast cancer.

†Cancer Genomics Consortium Levels of Evidence

Tier Data Source(s) Interpretation
1 FDA approved therapies, professional guidelines, multiple large clinical studies Strong evidence supporting clinical utility of variant(s) for diagnosis, selection of therapies, or predicting disease outcome
2 One large study or multiple case reports Emerging evidence supporting clinical utility of variant(s)
3 Case reports or expert opinion Unknown clinical significance
4 Published evidence indicating lack of pathogenicity of variant(s) Benign or likely benign


Table 3 - Genes with known hereditary risk associations in breast cancer. Table derived from Geiersbach et al., 2018 [PMID 32087595] with permission from Cancer Genetics.

Gene Associated Syndrome; Breast Cancer Subtype
ATM Ataxia telangiectasia syndrome
BARD1 TNBC
BRCA1 BRCA-Related Breast/ Ovarian Cancer Syndrome; TNBC
BRCA2 BRCA-Related Breast/ Ovarian Cancer Syndrome; TNBC
CDH1 Hereditary Diffuse Gastric Cancer and Lobular Breast Cancer
CHEK2 Inherited breast cancer
NBN Nijmegen Breakage Syndrome
NF1 Neurofibromatosis type 1
PALB2 Fanconi anemia
PTEN Cowden syndrome
RAD51C TNBC
RAD51D TNBC
STK11 Peutz-Jeghers syndrome
TP53 Li-Fraumeni syndrome

Abbreviations: TNBC, triple negative breast cancer.

Reference

  1. ↑ Geiersbach, Katherine B.; et al. (2020-06). "Current concepts in breast cancer genomics: An evidence based review by the CGC breast cancer working group". Cancer Genetics. 244: 11–20. doi:10.1016/j.cancergen.2020.02.002. ISSN 2210-7762. PMID 32087595 Check |pmid= value (help). Check date values in: |date= (help)
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