Breast Cancer Table: Recurrent Genomic Alterations Detected by Chromosomal Microarray

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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
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
STK11 Peutz-Jeghers syndrome
TP53 Li-Fraumeni syndrome

Abbreviations: TNBC, triple negative breast cancer.


  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)