This suggests that acquired resistance to AIs is related to the PI3K/Akt/mTOR signaling pathway, a major regulator of the cell cycle [19, 20], and that a SERD or SERM plus a targeted therapy that inhibits the PI3K/Akt/mTOR pathway may have superior efficacy for breast cancer with secondary resistance to AIs. The gene discussed is AKT1; the disease is breast carcinoma.