PIK3CA and neoplasm: A greater level of PIK3CA mutation in normal breast than in breast tumors is consistent with the ideas that PIK3CA mutations are early drivers of multiclonal tumor origin, that multiple mutations are needed to overcome normal tissue homeostatic mechanisms, and that clonal selection and metapopulation dynamics drive the outgrowth of tumor cells, which may be predominantly other than PIK3CA-mutant (yet retaining minor PIK3CA mutant subpopulations), although some percentage of the time predominantly PIK3CA-mutant tumors do arise [23].