Breast Cancer Table: Recurrent Genomic Alterations Detected by Chromosomal Microarray

From Compendium of Cancer Genome Aberrations
This is the approved revision of this page, as well as being the most recent.
Jump to navigation Jump to search

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. Table derived from Geiersbach et al., 2018 [PMID 32087595] with permission from Cancer Genetics.

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

* Indicates genes more commonly activated by amplification than by sequence variation

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)