Breast Cancer Table: Recurrent Genomic Alterations Detected by Chromosomal Microarray
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 |
Abbreviations: TNBC, triple negative breast cancer.
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.