Table 2. Common Genomic Alterations in Breast Cancer and Existing Therapeutic Options.
Commonly mutated genes in breast cancer are grouped by pathway and listed with estimated mutation frequency. Agents currently in clinical trials targeting each pathway are listed. Adapted from Metzger-Filho & Polyak.42
| PI3-Kinase Pathway | ERBB2/ HER2 |
Fibroblast Growth Factor |
Insulin-Like Growth Factor |
Estrogen Receptor |
BRCA Mutation |
c-MET | ||||
|---|---|---|---|---|---|---|---|---|---|---|
|
| ||||||||||
| PIK3CA (34%), PIK3R1 (2%), AKT1 (2%) | ERBB2 (14%) | FGFR1 (13%), FGFR2 (3%), FGFR3 (2%) |
IGF1R (6%), IGF2R (3%), IGF1 (1%) |
ESR1 (4%) | BRCA1 (4%), BRCA2 (4%) |
MET (2%) | ||||
|
| ||||||||||
| Inhibitors | PI3K Inhibitors | mTOR inhibitors | AKT inhibitors | PI3K/mTOR Inhibitors | PARP Inhibitors | |||||
| Buparlisib (BKM120) | Everolimus | GDC-0068 | BGT226 | Trastuzumab | AZD4547 | BMS-754807 | Tamoxifen | Olaparib | SGX523 | |
| Pictilisib (GDC-0941) | Temsirolimus | MK2206 | GDC-0980 | T-DM1 | BGJ398 | Cixutumumab | Toremifene | Veliparib | INC280 | |
| BYL120 | AZD8055 | GSK2141795 | PKI-587 | Pertuzumab | Dovitinib | Dalotuzumab | Anastrazole | Rucaparib | Tivantinib | |
| GDC-0032 | INK128 | XL765 | Lapatinib | Lucitinib (E-3810)** | Figitumumab | Letrozole | BMN-673 | PF-02341066* | ||
| INK1117 | Afatinib | HGS1036 | Ganitumab | Exemestane | CEP-9722 | Cabozantinib** | ||||
| PF-04691502 | Canertinib | BAY1163877 | Linsitinib | Fulvestrant | E7016 | GSK1363089 | ||||
| PX-866 | Dacomitinib | GSK3052230 | MEDI-573 | INO-1001 | ARQ197 | |||||
| XL147 | Neratinib | MK4827 | ||||||||
| MM-121 | ||||||||||
*
Also inhibits ALK
**
Also inhibits VEGFR