Among gene alterations, ESR1 amplification and other targeted genes involved in signaling pathways (PI3K/AKT/MTOR, ERBB2, FGFR, CDK4/CDK6, MDM2–TP53, histone deacetylases) are known to cross-talk with the ER pathway in breast cancer [40]. The gene discussed is PIK3CA; the disease is breast cancer.