AKT1 and breast cancer: Affected individuals develop multiple systemic hamartomas and have a cumulative lifetime risk of breast cancer of 85%.1 Approximately 80% of patients with Cowden syndrome have a germline inactivating mutation in PTEN (10q23.3).2PTEN acts as a tumor suppressor gene via numerous mechanisms,3 one of which is antagonizing the PI3K/AKT/mTOR signaling pathway by dephosphorylating phosphatidylinositol (3,4,5)-trisphosphate (PIP3).