Utidelone Plus Bevacizumab for Advanced Breast Cancer With Brain Metastases

Inclusion Criteria: 1. Aged ≥ 18 years; histologically or cytologically confirmed invasive breast cancer with metastatic disease; patients without pathologically or cytologically confirmed metastatic disease must have physical or radiological proof of metastasis; 2. With measurable CNS disease, defined as at least one parenchymal brain lesion that can be accurately measured in at least one dimension by local radiology; 3. Previously treated with at least one anthracycline and one taxane (as neoadjuvant therapy, adjuvant therapy, palliative therapy, or both); 4. Patients in cohort 2 have failed trastuzumab and pyrotinib treatment; 5. Prior unproven treatment progression with utidelone or bevacizumab; 6. ECOG PS of 0-1 and life expectancy exceeding 12 weeks; 7. Normal organ and bone marrow function; normal blood sample within one week before enrollment (as determined by the laboratory's normal values in each center), including WBC ≥ 3.0 x 109/L, ANC ≥ 1.5×109/L, PLT ≥ 100×109/L; normal kidney and liver function within one week before enrollment (as determined by the laboratory's normal values in each center), including TBIL ≤ 1.5 ULN, SGPT/ALT ≤ 2.5 ULN (≤ 5 ULN in patients with liver metastases), SGOT/AST ≤ 2.5 ULN, Ccr ≥ 60 ml/min; 8. Neurological lesions must be \< grade 2 according to NCI CTCAE version 5.0 within four weeks before enrollment; 9. Without major organ dysfunction or heart disease; 10. Those of childbearing potential should use appropriate contraception before and during study period. Exclusion Criteria: 1. Patients with leptomeningeal metastases who are not adequately treated by dehydration, hormone therapy, or urgently need radiotherapy; 2. Presence of effusions that cannot be controlled by drainage or other treatment (e.g., massive pericardial, thoracic, or abdominal effusions); 3. Patients received WBRT, chemotherapy, major surgery, targeted therapy or immunotherapy within two weeks before enrollment, received endocrine therapy within one week before enrollment, or received nitrosourea or mitomycin based chemotherapy within six weeks before enrollment； 4. Participation in another clinical trial within four weeks before enrollment； 5. History of grade 3 or 4 allergic events to bevacizumab or utidelone; 6. Contraindications to MRI gadolinium-based contrast agents, such as pacemakers, shrapnel or intraocular foreign bodies; 7. Other malignancies within three years, except for cured cervical carcinoma in situ, cutaneous basal cell carcinoma, or cutaneous squamous cell carcinoma; 8. More than two seizures within four weeks before enrollment; 9. Insufficiently controlled hypertension, or history of hypertensive crisis or hypertensive encephalopathy; 10. CNS hemorrhage of grade 2 or higher within 12 months before enrollment; 11. NYHA class II or severe congestive heart failure, or history of myocardial infarction or unstable angina within six months; 12. History of hemoptysis within six months before enrollment, or evidence of bleeding tendency or significant coagulation dysfunction within one month; 13. Receiving full dose of warfarin or equivalent currently, or using aspirin (325 mg/day) within ten days; 14. Needs for major surgery, open biopsy or with major trauma within 28 days or during the study period; 15. History of abdominal fistula or gastrointestinal perforation within six months； 16. Presence of unhealed wound, active ulcer or untreated fracture; 17. Any other condition inappropriate for this study deemed by the investigator.