|  |  | 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% | |
PTEN | Loss-of-function mutation or reduced expression | Hyperactivation of PI3K signaling | 29-44% | 22% | 67% | |
PIK3CA (p110α/PI3K) | Activating mutation | Hyperactivation of PI3K signaling | 28-47% | 23-33% | 8-25% | |
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% | |
FGFR1 | Amplification, activating mutation | Hyperactivation of FGFR signaling (PI3K, MEK) | 8.6-11.6% | 5.4% | 5.6% | |
RPS6K1 (p70S6K) | Amplification | Unknown | Â | 3.8-12.5% of all cases | Â | [111] |
INPP4B | Reduced expression or genomic loss | Hyperactivation of PI3K signaling | 10-33% | 54% | 53% | |
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% | |
AKT2 | Amplification | Hyperactivation of AKT | Â | 2.8% of all cases | Â | [115] |
EGFR | Amplification | Hyperactivation of EGFR signaling (PI3K, MEK) | Â | 0.8% of all cases | Â | [116] |
PDK1 | Amplification or overexpression | Hyperactivation of PDK1 (AKT, TORC1) | 22% | 22% | 38% | [117] |
KRAS | Activating mutation | Hyperactivation of PI3K and MEK | Â | 4-6% of all cases | Â |