Sirolimus for Injection (Albumin-bound) Combined With Fulvestrant for HR+/HER2- Advanced/Metastatic Breast Cancer Patients Previously Treated With CDK4/6 Inhibitors

Inclusion Criteria:

1. Aged 18 or above, regardless of gender; female patients must be postmenopausal,or premenopausal/perimenopausal.

2. Pathologically confirmed HR+, HER2- breast cancer.

3. Locally advanced or metastatic breast cancer, not suitable for curative surgeryor radiotherapy, and no current clinical indication for chemotherapy.

4. Previously received at least one, up to two lines of systemic therapy (including at least one line of endocrine therapy combined with CDK4/6inhibitor therapy).

5. At least one measurable lesion according to RECIST 1.1 criteria.

6. Willing to provide tumor and/or blood samples for biomarker testing; if unableto provide, subject to investigator and sponsor evaluation for eligibility.

7. ECOG performance status score of 0-1.

8. Investigator-assessed life expectancy ≥6 months.

9. Adequate organ and bone marrow function.

10. Premenopausal female patients using LHRH agonists to suppress ovarian functionmust agree to use two acceptable forms of highly effective contraception duringthe study and for 2 years after stopping study treatment; female patients ofchildbearing potential must have a negative pregnancy blood test beforestarting study treatment and must not be breastfeeding.

11. Male patients must agree to use barrier contraception (i.e., condoms) duringthe study and for 2 years after stopping study treatment; for men with futurefertility plans, sperm freezing is recommended before starting study treatment.

12. Participants must provide informed consent before the trial and voluntarilysign the written ICF.

Exclusion Criteria:

1. Previous pathological diagnosis of HER2-positive breast cancer.

2. Patients judged by the investigator to be unsuitable for endocrine therapy.

3. Patients who have previously received PI3K/AKT/mTOR inhibitors, fulvestrant, orother ER-targeted therapies (including oral SERDs, ER protein degraders PROTAC,etc.).

4. Received chemotherapy, radiotherapy, biological therapy, targeted therapy,immunotherapy, or other anti-tumor treatments within 4 weeks beforerandomization.

5. Received other unapproved investigational drugs within 4 weeks beforerandomization.

6. Underwent major surgery within 4 weeks before randomization or has not fullyrecovered from any previous invasive procedures.

7. Received systemic glucocorticoids (prednisone >10 mg/day or equivalent) orother immunosuppressive treatments within 2 weeks before randomization.

8. Had an infection within 2 weeks before randomization requiring systemic (oralor IV) anti-infective treatment (uncomplicated urinary tract infections orupper respiratory tract infections excluded).

9. Received inactivated or live attenuated vaccines or COVID-19 vaccines within 4weeks before randomization.

10. Used strong inhibitors or inducers of CYP3A4 hepatic metabolic enzymes within 2weeks before randomization or still need to continue using such drugs.

11. Diagnosed with other malignancies within 5 years before randomization.

12. Suffering from severe cardiovascular or cerebrovascular diseases.

13. Adverse reactions from previous anti-tumor treatments have not recovered toCTCAE 5.0 grade ≤1.

14. Active leptomeningeal disease or poorly controlled central nervous systemmetastases.

15. Presence of pleural/abdominal effusion or pericardial effusion with clinicalsymptoms or requiring symptomatic treatment.

16. Known bleeding tendency (constitution) or coagulation disorders.

17. History of severe lung diseases such as interstitial lung disease and/orpneumonia, pulmonary hypertension, or radiation pneumonitis requiringglucocorticoid treatment.

18. Known hypersensitivity or intolerance to any component of the study drug or itsexcipients, or LHRH agonists (if applicable).

19. History of autoimmune diseases (except tuberous sclerosis), immunodeficiencydiseases, including HIV-positive, or other acquired or congenitalimmunodeficiency diseases, or organ transplant history.

20. Active HBV, HCV, syphilis, or tuberculosis infection.

21. Other conditions judged by the investigator to be unsuitable for participationin this study.