PIK3CA mutations activate the PI3K-PTEN-AKT pathway which is downstream from both the EGFR and the RAS-RAF-MAPK pathways.The somatic mutations found thus far in PIK3CA are oncogenic, and the majority of them are clustered within exon 9 and 20 (helical and kinase domains), with 80% of the identified mutations found within three hotspot: E542K, E545K, and H1047R. PIK3CA mutations are often found in hormone receptor positive breast cancer and have been associated with resistance to anti-EGFR therapy in some studies but not in others.