This is a multicenter, open-label, phase Ib study designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CYH33 administered orally in combination with standard-of-care ET ± CDK4/6 inhibitor therapies for the treatment of locally advanced, recurrent or metastatic hormone-receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) breast cancer. Patients will be enrolled in two stages, including dose exploration phase (Stage 1) and dose expansion phase (Stage 2) of each cohort.

Main Inclusion Criteria:

1. Provide informed consent voluntarily.
2. Male and female patients ≥ 18 years of age.
3. Patient must have a histologically or cytologically documented locally advanced, recurrent or metastatic breast cancer.
4. In case of women, both premenopausal and postmenopausal patients can be enrolled in the study.
5. Confirmed diagnosis of HR+, HER2- breast cancer.
6. For Stage 1 dose exploration phase, patients with or without PIK3CA mutation may be enrolled; For Stage 2 dose expansion phase, patients with PIK3CA mutations are required.
7. Patient must have evidence of disease radiological progression after previous endocrine therapy, or other systemic therapy.
8. Patient has measurable disease per RECIST v1.1.
9. ECOG ≤ 1.
10. Patient must have adequate organ and bone marrow function.

Main Exclusion Criteria:

1. Previously received any anticancer therapy within 28 days or 5 times of half-lives prior to the first dose of the study treatment.
2. Previously received treatment with any PI3Kα inhibitor, AKT inhibitor, or mTOR inhibitor.
3. Radical radiation therapy within 4 weeks prior to the first dose of the study treatment.
4. Patient with an established diagnosis of diabetes mellitus.
5. Any other concurrent disease with potential risk of insulin resistance or current use of medication with potential risk of insulin resistance.
6. Patient with clinically significant cardiovascular disease.