In breast cancer, gain-of-function mutations in the PI3K catalytic subunit alpha gene (PIK3CA) and loss of phosphatase and tensin homolog (PTEN) function are common genomic events, either of which can result in an activated PI3K pathway phenotype and induction of oncogenic transformation, as demonstrated in preclinical models [1]–[5]. The gene discussed is PIK3CA; the disease is breast cancer.