⁃ Histologically confirmed HR+/HER2- breast cancer (primary or metastatic):

• HR+ defined as ER+ with or without PRg+

• HER2- defined as IHC 0 or 1+, or IHC 2+/ISH-

⁃ Patient with tumours harbouring at least one PIK3CA/AKT1/PTEN qualifying alteration detected by a validated test (including NGS on tissue, cell block, or if tissue/cell block is not available, on ctDNA, as per protocol requirements. If alteration is initially detected by a method other than NGS, NGS on tissue/cell block must be performed within 45 days unless not available, which must be documented.)

⁃ Metastatic or locally advanced disease with radiological or objective evidence of recurrence or progression.

⁃ Patients must have received treatment with an ET in combination with CDK4/6i and have:

• Radiological evidence of breast cancer recurrence or progression while on, or within 12 months of the end of (neo)adjuvant treatment with an ET with CDK4/6i, OR

• Radiological evidence of progression while on prior ET with CDK4/6i administered as a treatment line for locally advanced or metastatic breast cancer.

⁃ Informed consent

⁃ Eastern Cooperative Oncology Group (ECOG)/ World Health Organisation (WHO) performance status ≤ 2 at enrollment (not more than 20% of patients with ECOG PS2 will be allowed).

⁃ Reproduction:

• Women of childbearing potential (WOCBP) patients with ovarian suppression induced by LHRH agonist should agree to use 2 forms of highly effective methods of accepted contraception to prevent pregnancy.

• Male patients should use barrier contraception.