Breast Cancer: Recurrent Genomic Alterations

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.

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.