Inclusion criteria

Eligible patients ≥18 years old had histological or cytological confirmation of ER+ advanced or MBC refractory to standard therapies and confirmation of an eligible PTEN alteration in tumor tissue by local testing. Eligible PTEN alterations were defined as a deleterious mutation in PTEN or copy loss of the PTEN gene³¹. Further inclusion criteria were measurable disease by RECIST v1.1, WHO performance status 0–1, and minimum life expectancy of 12 weeks. Key exclusion criteria included active central nervous system metastases, prior treatment with catalytic AKT inhibitors (prior exposure to all other agents in the PI3K/AKT/mTOR pathway, including allosteric AKT inhibitors, was allowed), and clinically significant abnormalities of glucose metabolism [defined by any of the following criteria: i. diagnosis of diabetes mellitus type I or II (irrespective of management); ii. baseline fasting glucose value of ≥7 mmol/L (fasting is defined as no calorific intake for at least 8 h); and iii. glycated hemoglobin >8% (>64 mmol/mol)].

All patients provided written informed consent, the institutional review boards or independent ethics committees of all investigational sites approved the protocol, and the study was performed in accordance with the Declaration of Helsinki, Good Clinical Practice, and the AstraZeneca policy on bioethics³².