In recent years, several inhibitors targeting the PI3K/AKT/mTOR pathway have been approved by the FDA to treat ER-positive, HER2-negative, high-risk and metastatic breast cancer, such as alpelisib (a PI3K inhibitor) and everolimus (an mTOR inhibitor), often combined with standard endocrine therapy like fulvestrant or aromatase inhibitors, particularly when a PIK3CA mutation is present in the tumor; AKT inhibitors like capivasertib may also be considered in some cases depending on the specific genetic profile of the tumor. Here, ESR1 is linked to neoplasm.