Germline PTEN loss-of-function mutations may result in dominant AKT activation as a driving oncogenic event in Cowden-related breast tumors.5 Preclinical evidence suggests that cancers with AKT activation have increased sensitivity to AKT inhibition.6 Preliminary clinical evidence is derived from phase I and II trials in patients with breast cancers bearing somatic mutations in the PI3K/AKT/mTOR pathway.7-11. The gene discussed is PTEN; the disease is breast cancer.