PTPRD mutation was previously reported in the TCGA cohort,40 both in vitro and in vivo experiments confirmed that PTPRD acted as a negative regulator of breast cancer metastasis, possibly via downstream IL-6/STAT3 cascade and E2F regulation.41,42TSC2 was a putative tumor suppressor gene in the PI3K/AKT/mTOR pathway and its mutation was also observed in HR+/HER2− metastatic breast cancers in a multi-center cohort.43 However, it was also revealed to play a protumorigenic role in breast cancer. This evidence concerns the gene AKT1 and breast cancer.