Combination Followed by Maintenance Chemotherapy Versus CDK4/6 Inhibitor Combined With Endocrine Therapy for HR Low/HER2-negative Advanced Breast Cancer: a Prospective, Randomized, Open-label Phase Ⅱ Clinical Trial

Inclusion Criteria:

1. age ≥18 years old; Invasive breast cancer with metastatic disease confirmed byhistological or cytological examination; Patients without pathologically orcytologically confirmed metastatic disease should have clear evidence of metastasisby physical examination or radiological studies;

2. The most recent pathological report of biopsy confirmed HR low expression and HER2negative.

3. HR low expression was defined as 1-50% ER expression by immunohistochemistry (IHC); Or ER<1% and PR≥1%; Patients with ER expression of 1-10% or ER-/PR-positive patients were eligible for inclusion after careful evaluation bythe investigator, and those with a small tumor burden and candidates forendocrine therapy were eligible.

4. HER2-negative definition: IHC 0 or 1+; If the IHC was 2+, it was confirmednegative by fluorescence in situ hybridization (FISH).

5. at least one measurable lesion;

6. No previous salvage chemotherapy for metastatic disease was required, and first-lineendocrine therapy was allowed;

7. no previous CDK4/6 inhibitor; For adjuvant CDK4/6i treatment, recurrence andmetastasis were required more than 1 year after drug withdrawal.

8. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, life expectancyis more than 12 weeks;

9. Adequate function of major organs.

10. All adverse events recovered to grade 1 or less before enrollment (NCI CTCAE version 5.0);

11. patients without major organ dysfunction and heart disease;

12. Women and men of childbearing potential must agree to use appropriate contraceptionbefore and during study participation.

Exclusion Criteria:

1. symptomatic, uncontrolled brain or leptomeningeal metastases; Patients who hadreceived previous systemic radical treatment for brain metastases (radiotherapy orsurgery), if stable disease had been maintained for at least 1 month as confirmed byimaging, and if systemic hormone therapy (dose 10mg/ day prednisone or othereffective hormones) for more than 2 weeks without clinical symptoms.

2. patients received radiotherapy, chemotherapy, major surgery, targeted therapy orimmunotherapy within 2 weeks before enrollment; Patients received endocrine therapywithin 1 week before enrollment. Chemotherapy with nitrosourea or mitomycin wasadministered within 6 weeks before enrollment.

3. participated in other clinical trials of new drugs within 4 weeks before enrollment;

4. there can not be controlled by drainage or pneumatic methods third space effusion;

5. patients with other malignant tumors within the past 3 years, excluding radicalcervical carcinoma in situ, skin basal cell carcinoma or skin squamous cellcarcinoma;

6. suffering from serious or uncontrolled diseases, including but not limited to: 1)active viral infection, such as HIV or HBV active (HbsAg positive and HBV-DNA≥103,hepatitis C antibody positive); 2) history of severe cardiovascular disease:uncontrolled hypertension; Myocardial infarction, unstable arrhythmia, congestiveheart failure, pericarditis, myocarditis, etc. Patients with NYHA class ⅲ-ⅳ cardiacdysfunction, or left ventricular ejection fraction (LVEF) 50% by echocardiography;

3. severe infection (e.g., intravenous antibiotic, antifungal, or antiviral therapyaccording to clinical practice) within 4 weeks prior to the first dose orunexplained fever during screening/before the first dose; 38.3°C (fever due tocancer, as judged by the investigator, was eligible);

7. patients with a history of psychotropic drug abuse and unable to abstain or withmental disorders; Or accompanied by swallowing and absorption dysfunction;

8. patients with other concomitant diseases that seriously endanger the safety ofpatients or affect the completion of the study according to the judgment of theinvestigators;

9. patients with known history of allergy to the components of this regimen; A historyof immunodeficiency, including testing positive for HIV, HCV or other acquired orcongenital immunodeficiency disorders, or a history of organ transplantation;

10. pregnant or lactating women;

11. Patients deemed unsuitable for inclusion by the investigators.