In addition, in the abovementioned Shorther trial, the observed association between phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) mutations and more favorable prognosis was hypothesized to be linked, at least in part, to immune infiltration, given the fact that PIK3CA-mutated tumors also harbored higher TILs as compared to PIK3CA wild-type tumors [44], thus adding a further layer of complexity on HER2+ BC heterogeneity. This evidence concerns the gene ERBB2 and breast cancer.