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). The gene discussed is PIK3CB; the disease is breast cancer.