Hyper-activation of the pathway is common in human cancers and can be achieved in a number of ways, including mutation of PIK3CA. PIK3CA, the gene encoding the alpha catalytic subunit of the kinase, is mutated in approximately 15% of colorectal tumours and approximately 30% of breast cancers, with most mutations occurring at three hotspots, E542K, E545K and H1047R[4]–[9]. The gene discussed is PIK3CA; the disease is breast cancer.