PIK3CA and breast cancer: Further, studies have noted a high degree of intrapatient cellular heterogeneity and discordant PIK3CA status between CTCs and matched primary tumors [18,28,35,36], of which PIK3CA was one of two genes (among >2200 COSMIC mutations analyzed) frequently mutated in CTCs, cfDNA, and matched primary tumor in HER2- breast cancer [36].