Table I.
Molecular subtype signatures of breast cancer.
| Classification | Signature genes | Signaling pathways | Clinical grade | Therapeutic options | 5-year survival rate | p53-mutation | Refs. |
|---|---|---|---|---|---|---|---|
| Luminal A | Marker genes: ER+ and/or PR+, HER2−, CK8/18+; GATA-3, XBP-1, FOXA1 and ADH1B gene overexpression | Estradiol response | I | Tamoxifen; anastrozole (Arimidex) | 95% | 13% | (11,14,23,24,26) |
| Luminal B | Marker genes: ER+ and/or PR+, HER2+, CK8/18+, FGFR1, HER1, Ki-67 and/or cyclin E1, CCNB1 and MYBL2 gene overexpression | IGF-1 FGF PI3K |
I (III also observed) | Bevacizumab combined with paclitaxel, tamoxifen combined with small-molecule inhibitors or antibodies against IGF-1R/IR, FGF, FGFR, PI3K and EGFR/HER2 | 50% | 40% | (11,12,14,17,70, 84,110,111) |
| ErbB2/HER2+ | Marker genes: ER− and/or PR−, HER2+ and GRB7 overexpression | IGF-1 HER2 |
More likely III | Trastuzumab (Herceptin), lapatinib (Tykerb). For patients with resistance to trastuzumab, combine with a PI3K/mTOR inhibitor |
30% | 71% | (11,14,112,113) |
| Basal-like | Marker genes: ER− and/or PR−, HER2−, CK5/6+, CK14+, CK17+, EGFR+ HER1 and/or c-Kit, FOXC1, p63, P-cadherin, vimentin and laminin overexpression | IGF-1 Wnt/β-catenin |
More likely III | Chemotherapy; antiangiogenic agents; platinum salts; PARP inhibitors | 30% | 83% | (11,12,14,23, 112,114–117) |
| Normal | Marker genes: ER− and/or PR−, breast-like HER2−, CK5/6−, CK14−, CK17−, EGFR and ADH1B overexpression | 50% | 33% | (11,14,26) |
ER, estrogen receptor; PR, progesterone receptor; HER2, human epidermal growth factor receptor 2; GATA-3, GATA binding protein 3; XBP-1, X-box binding protein 1; FOXA1, forkhead box A1; FGFR1, fibroblast growth factor receptor 1; MYBL2, myeloblastosis oncogene-like 2; CK, cytokeratin; ADH, alcohol dehydrogenase; GRB, growth factor receptor-bound protein; IGF, insulin-like growth factor; PI3K, phosphatidylinositol-3-kinase; mTOR, mammalian target of rapamycin; PARP, poly ADP ribose polymerase.