The activation of both PI3K/AKT and STAT3 signaling has been recognized to shape the tumor immune microenvironment and modulate the anti-tumor immune response, which emphasizes the therapeutic potential of targeting both oncogenic and immune checkpoint pathways (e.g. PD-1 or CTLA4) in drug-resistant HER2-positive breast tumors [34]. This evidence concerns the gene PIK3CA and breast neoplasm.