Therefore, in light of the fact that PIK3CA mutations are associated with a phenotype of relatively low mTOR signaling and better outcome in ER+/HER2- breast cancer [5],[6], it may be that decreased PTEN level, and perhaps the levels of other phosphatases regulating this pathway such as INPP4B [47], represents an important mechanism resulting in the more aggressive phenotype seen in luminal B breast cancer [48]. This evidence concerns the gene ESR1 and breast cancer.