Table 1.
Frequencies of changes of PAM pathway in different molecular subtypes of breast cancer.
| Gene (Protein) |
Alteration | Effect on Signaling | Correlation with Prognosis | Frequency | Reference | |||
|---|---|---|---|---|---|---|---|---|
| Luminal (ER+) | HER2+ | TNBC (ER−, PR−, HER2−) | ||||||
| A | B | |||||||
| PTEN | Inactivation and mutation/reduced expression | over activation of PI3K signaling | Negative in TNBC | 29–44% | 22% | 67% | [33,34,35] | |
| PIK3CA (p110α/PI3K) |
Activating mutation | Hyperactivation of PI3K signaling | * Positive in luminal, negative in metastatic/HER2+ breast cancer |
47% | 33% | 23–39% | 8–25% | [33,36,37,38] |
| PIK3CB (p110β/PI3K) |
Amplification /Mutation |
PIP3 accumulates and activates AKT | Irrelevant | 5% | [29,39] | |||
| PIK3R1 (p85α/PI3K) |
Inactivating mutation | Derepression of catalytic activity of p110α | - | 2% of Early breast cancer 11% of Metastatic breast cancer |
[40,41] | |||
| AKT1 | Activating mutation | Hyperactivation of AKT | Irrelevant | 2.6–7.4% | [33,42,43,44] | |||
| AKT2 | Amplification | Irrelevant | 2.8–4% | [18] | ||||
| AKT3 | Amplification | Positive in luminal A breast cancer | 15% | [40] | ||||
| PDK1 | Amplification | Hyperactivation of AKT | - | 20–38% | [45] | |||
| (mTOR) | p-mTOR expression | Hyperactivation of mTOR | Negative in TNBC | 39% | 37.5–72.1% | [46] | ||
* Positive: Associated with a better prognosis; Negative: Associated with a worse prognosis; Irrelevant: No significant correlation with prognosis; p-mTOR: phosphorylated mTOR.