The phosphatidylinositol 3-kinase (PI3K) pathway is one of the most altered pathways in luminal breast cancer, and large efforts to unravel endocrine resistance have pointed to aberrant signaling of PI3K, e.g., by PIK3CA mutations, loss of PTEN, or downstream protein phosphorylation [19–23]. The gene discussed is PIK3CA; the disease is breast cancer.