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Table 1 Phosphatidylinositol 3-kinase pathway alterations in human breast cancers by molecular subtype
| Frequency | ||||||
|---|---|---|---|---|---|---|
| Gene (protein) | Alteration | Effect on signaling | Luminal (ER+) | HER2+ | Basal (TN) | Reference |
| ErbB2 (HER2) | Amplification or overexpression | Hyperactivation of ErbB2 signaling (PI3K, MEK) | 10% | ~100% | 0% | [30–32] |
| PTEN | Loss-of-function mutation or reduced expression | Hyperactivation of PI3K signaling | 29-44% | 22% | 67% | [6, 8, 104, 105] |
| PIK3CA (p110α/PI3K) | Activating mutation | Hyperactivation of PI3K signaling | 28-47% | 23-33% | 8-25% | [6, 52, 66–68, 105–107] |
| PIK3CB (p110β/PI3K) | Amplification | Unknown | 5% of all cases | [62] | ||
| IGF1R and INSR (IGF-1R, InsR) | Receptor activation, IGF1R amplification | Activates IGF-IR/InsR signaling (PI3K, MEK) | 41-48% | 18-64% | 42% | [108, 109] |
| FGFR1 | Amplification, activating mutation | Hyperactivation of FGFR signaling (PI3K, MEK) | 8.6-11.6% | 5.4% | 5.6% | [63, 110] |
| RPS6K1 (p70S6K) | Amplification | Unknown | 3.8-12.5% of all cases | [111] | ||
| INPP4B | Reduced expression or genomic loss | Hyperactivation of PI3K signaling | 10-33% | 54% | 53% | [64, 112] |
| PIK3R1 (p85α/PI3K) | Inactivating mutation | Derepression of catalytic activity of p110α | 2% of all cases | [113] | ||
| AKT1 | Activating mutation | Hyperactivation of AKT | 2.6-3.8% | 0% | 0% | [65, 66, 106, 114] |
| AKT2 | Amplification | Hyperactivation of AKT | 2.8% of all cases | [115] | ||
| EGFR | Amplification | Hyperactivation of EGFR signaling (PI3K, MEK) | 0.8% of all cases | [116] | ||
| PDK1 | Amplification or overexpression | Hyperactivation of PDK1 (AKT, TORC1) | 22% | 22% | 38% | [117] |
| KRAS | Activating mutation | Hyperactivation of PI3K and MEK | 4-6% of all cases | [118, 119] | ||
