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| + | '''Table 1 - Clinically significant copy number alterations in breast cancer''' |
| {| class="wikitable" | | {| class="wikitable" |
| |'''Alteration''' | | |'''Alteration''' |
Line 6: |
Line 7: |
| |- | | |- |
| |1q gain | | |1q gain |
− | | unknown | + | |unknown |
| |2 | | |2 |
| |Most common copy number alteration, often with 16q loss; all subtypes | | |Most common copy number alteration, often with 16q loss; all subtypes |
Line 69: |
Line 70: |
| |2 | | |2 |
| |METABRIC IntClust1, ER Positive | | |METABRIC IntClust1, ER Positive |
| + | |} |
| + | '''Table 2 - Major clinically significant genes associated with somatic sequence alterations in breast cancer''' |
| + | {| 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 |
| + | |- |
| + | |''FGFR1-4'' |
| + | |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) |
| + | |- |
| + | |''NTRK1-3'' |
| + | |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. |
| + | |
| + | '''Cancer Genomics Consortium Levels of Evidence''' |
| + | {| class="wikitable" |
| + | |'''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''' |
| + | {| class="wikitable" |
| + | |'''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 |
| |} | | |} |