HRS-8080 versus doctor‑chosen treatments for locally advanced or metastatic breast cancer

Inclusion Criteria:

1. Women aged 18 to 75 years old (including both values).
2. ECOG Physical Strength Status (PS) : 0 to 1 point.
3. Patients with locally advanced or metastatic breast cancer confirmed by histology.
4. Patients previously received 1-2 lines of endocrine therapy.
5. Patients received no more than one line of chemotherapy in the recurrence/metastasis stage.
6. Menstrual status (meeting any of the following conditions) : a) After bilateral ovariectomy; b) Age ≥60 years old; c) Age \< 60 years old, natural menopause ≥12 months, without receiving chemotherapy, tamoxifen (TAM), tolemiphene or ovarian castration in the past year, follicle-stimulating hormone (FSH) and estradiol are within the postmenopausal range; d) For patients under the age of 60 who are taking TAM or tolemiphene, the levels of FSH and estradiol are within the postmenopausal range; e) Premenopausal or perimenopausal patients received luteinizing hormone-releasing hormone (LHRH) agonist treatment during the study period, and the treatment was initiated at least 14 days before the start of the study.
7. Patients comply with any of the following provisions of the RECIST v1.1 standard: a) There is at least one extracranial measurable lesion; b) If there are no measurable lesions as stipulated above, at least one osteolytic or mixed (osteolytic and osteogenic) bone lesion that can be evaluated by computed tomography (CT) or magnetic resonance imaging (MRI) exists.
8. Expected survival \> 6 months.
9. The functional level of the organs must meet the requirements.
10. Female with fertility must agree to use effective contraceptive measures for contraception during the study treatment period and within 7 months after the end of the study treatment period; Femalewith fertility must have a negative serum human chorionic gonadotropin (hCG) test within 7 days before enrollment in the study and must be in the non-lactation period.
11. Voluntarily participate in this clinical trial, be willing and able to abide by the procedures related to clinical visits and research, understand the research procedures and have signed the informed consent.

Exclusion Criteria:

1. Patients previously received other systemic anti-tumor treatments besides chemotherapy、endocrine therapy and CDK4/6i (prior use of PI3K inhibitors or AKT inhibitors is permitted for patients with known PIK3CA mutations or PIK3CA/AKT/PTEN alterations).
2. Nitrosorea or mitomycin was received within 6 weeks before the first study administration in this study; Have undergone major organ surgery, cytotoxic drugs, immunotherapy, , anti-tumor traditional or Chinese medicine medications within 4 weeks before the first study administration and within 4 weeks or 5 half lives (whichever is shorter) prior to the first study drug administration ; Have received endocrine therapy (referring to aromatase inhibitors \[AI\], etc.) and palliative radiotherapy within 2 weeks before the first study administration.
3. the date from the first study administration to the last CYP3A4 strong inducer administration is less than 28 days.
4. Patients with rapid disease progression and investigators determines that endocrine therapy is not suitable or tolerant.
5. Patients with active (uncontrolled by medical treatment or with clinical symptoms) brain metastases, cancerous meningitis, spinal cord compression, or a history of primary central nervous system tumors; Patients with brain metastases who have completed treatment at least 28 days before the first study administration, have stable symptoms and do not require hormone therapy may be enrolled as appropriate, but they must be confirmed to have no cerebral hemorrhage by cranial imaging examinations such as CT, MRI or venography.
6. A history of severe clinical cardiovascular diseases.
7. Patients with uncontrollable tumor-related pain as judged by investigators. Patients who need pain-relieving medication must have a stable pain-relieving medication plan before entering the study.
8. Patients who have received immunosuppressant or systemic hormone therapy for immunosuppression within 2 weeks prior to the first medication (dose \> 10 mg/d prednisone or other corticosteroid hormones of equivalent physiological dose), excluding nasal sprays or inhaled hormones.
9. The damage caused by other treatments previously received by patients did not recover to grade ≤1 in the Common Terminology Criteria for Adverse Events of the National Cancer Institute of the United States, Version 5.0 (NCI CTCAE v5.0) (excluding alopecia and other adverse events judged tolerable by investigators).
10. Severe infection exists within 4 weeks before the first study administration, including but not limited to infectious complications requiring hospitalization, bacteremia, severe pneumonia, etc. There was an active infection of CTCAE grade ≥2 requiring intravenous antibiotic treatment within 2 weeks before the first study administration.
11. Patients with arterial/venous thrombotic events that occurred within 6 months before the first study administration, such as cerebrovascular accidents, deep vein thrombosis and pulmonary embolism, etc.
12. Patients with clinically significant endometrial abnormalities, including but not limited to endometrial hyperplasia and dysfunctional uterine bleeding.
13. Untreated active hepatitis.
14. Patients with other malignant tumors within the past 5 years or is currently suffering from them, except for cancers with an extremely low risk of recurrence, including but not limited to radical cervical carcinoma in situ, cutaneous basal cell carcinoma and squamous cell carcinoma, and surgically treated papillary thyroid carcinoma, etc.
15. Patients with hereditary or acquired bleeding tendency (such as hemophilia, coagulation dysfunction, etc.).
16. Patients with a history of active autoimmune diseases, immunodeficiency, or diseases and syndromes requiring systemic steroid hormone or immunosuppressive drug treatment, or having other acquired (human acquired immunodeficiency virus \[HIV\] infection), congenital immunodeficiency diseases, or a history of organ transplantation (including allogeneic bone marrow transplantation).
17. There is one of the multiple factors that affect oral medication (such as inability to swallow and intestinal obstruction, etc.) or there are active gastrointestinal diseases or other diseases that may lead to factors that significantly affect drug absorption, distribution, metabolism or excretion (active, inflammatory bowel disease or chronic diarrhea, enteral syndrome or upper gastrointestinal surgery, including gastrectomy).
18. Patients in the acute infection stage or active tuberculosis and requiring drug treatment.
19. Patients known to be allergic to the HRS-8080 component.
20. Pregnant and lactating women, or those planning to become pregnant during the study period.
21. Patients with a clear history of neurological or mental disorders, or patients with a history of drug abuse or psychotropic medication abuse.
22. Patients with other serious physical or laboratory examination abnormalities that may increase the risk of participating in the study, or interfere with the research results, as well as those deemed unsuitable for participation in the study by investigators.