EGFR and breast cancer: The PI3K pathway is the most frequently mutated in breast cancer through different mechanisms, including (i) increasing PI3K activity by mutation and/or amplification of PIK3CA, PIK3CB, or PIK3R1, (ii) overexpression of activating signals, such as human epidermal growth factor receptor 2 (HER2), epidermal growth factor receptor (EGFR) or insulin-like growth factor 1 receptor signaling, (iii) overexpression of downstream effectors AKT1, AKT2, or PDK1, or (iv) loss of negative regulators such as PTEN and INPP4B (Miller et al., 2011).