In phase I clinical trials of metastatic, estrogen receptor (ER)-positive, HER2-negative breast cancers harboring PTEN loss-of-function and AKT1 E17K mutations, capivasertib plus fulvestrant was shown to be more tolerable and clinically effective than treatment with capivasertib alone, especially in fulvestrant pre-treated patients, including those who have a history of progression on fulvestrant, with most of the ≥ grade 3 adverse effects reported being diarrhea (5% vs. 10%), hyperglycemia (5% vs. 30%), and a rash (9% vs. 20%) [307, 344]. Here, ESR1 is linked to breast carcinoma.