By using retroviral- or transposon-based insertional mutagenesis screens in Pik3ca(E545K vs H1047R)-model mice, or deep sequencing of Pik3ca(E545K vs H1047R)-model tumors, the cooperative network associated with each Pik3ca mutant can be defined and new combination therapies developed for patients with analogous PIK3CA mutant breast tumors. Here, PIK3CA is linked to breast neoplasm.