PIK3CA and neoplasm: In general, the high heterogeneity observed for the primary tumor and the matching CTC in both, ESR1 and PIK3CA, suggests two possible conclusions: (1) that the primary tumor is genetically heterogeneous and metastatic lesions do not have missense mutations observed in PT, because they are derived from different subclones and/or (2) that dissemination could have occurred early on, before primary tumor cells acquired these specific mutations.