Bevacizumab added or not to T-DXd for HER2-low breast cancer with brain metastases

Inclusion Criteria:

1. ECOG score of 0 to 1.
2. Expected survival period greater than 12 weeks.
3. Histologically confirmed invasive HER2-low expressing breast cancer (specific definition: breast cancer patients with low expression of human epidermal growth factor receptor 2 (HER-2) as determined by pathological testing. Specifically: HER2 IHC 1+ or HER2 IHC++ with FISH/CISH negative. All specimens must be verified by the pathology department of the research participating center.
4. Tumor stage: recurrent or metastatic breast cancer; local recurrence must be confirmed by the researcher to be unable to undergo radical surgical resection.
5. Patients must have at least one lesion that has not previously received radiation therapy (measurable and/or non-measurable).
6. MRI or CT shows brain metastasis and meets one of the following conditions:

   i) Untreated brain parenchymal metastasis found by imaging screening; ii) Previously locally treated stable or progressive brain parenchymal metastasis and meets one of the following conditions:a) Imaging stability ≥4 weeks; b) New brain parenchymal metastasis found by MR or CT.
7. Received no more than 2 lines of chemotherapy after metastasis.
8. HR-positive patients must have previously received CDK4/6 inhibitor treatment, whether in the adjuvant treatment phase or in the recurrent metastatic phase.
9. Never used T-DXd or bevacizumab before.
10. The main organ functions are basically normal, meeting the following conditions:
11. Blood routine examination standards must comply with: HB≥90g/L (not transfused within 14 days); ANC≥1.5×10\^9/L; PLT≥75×10\^9/L;
12. Biochemical examination must comply with the following standards: TBIL≤1.5×ULN (upper limit of normal); ALT and AST≤3×ULN; if there is liver metastasis, ALT and AST≤5×ULN; serum Cr ≤1.5×ULN, endogenous creatinine clearance rate ≥30mL/min.
13. Allowed to use mannitol, hormone therapy before enrollment, but the drug treatment dose can be stable for at least one week without the need for an increase.
14. Female subjects with reproductive capacity need to use one medically recognized contraceptive method during the study treatment period and for at least 3 months after the last use of the study drug.
15. Subjects voluntarily join this study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion Criteria:

1. Received more than 2 lines of chemotherapy.
2. Used T-DXd or bevacizumab.
3. Meningeal metastasis.
4. Brain metastasis requiring emergency intervention treatment, or brain metastasis requiring treatment with more than 3mg/d of dexamethasone or equivalent medication.
5. Clinical significant or uncontrolled cardiac disease history, including congestive heart failure, angina, myocardial infarction within the past 6 months, or ventricular arrhythmia.
6. Ongoing adverse reactions of grade \>1 due to previous treatment. The exception is alopecia or those that the researcher believes should not be excluded. Such cases should be clearly documented in the investigator's notes.
7. Pregnant patients.
8. History of other malignancies within the past 5 years, excluding cured cervical carcinoma in situ, skin basal cell carcinoma, or skin squamous cell carcinoma.
9. Inability to swallow, chronic diarrhea, and intestinal obstruction, with multiple factors affecting drug intake and absorption.
10. Third space fluid accumulation (such as massive pleural effusion and ascites) that cannot be controlled by drainage or other methods.
11. Participated in another antitumor drug clinical trial within 4 weeks before the first administration of the study drug.
12. Long-term non-healing wounds or incompletely healed fractures.
13. Known HBV or HCV infection during the active phase or HBV DNA ≥500, or chronic phase with abnormal liver function.
14. Active primary immunodeficiency, known HIV test positive.
15. Uncontrolled infection requiring intravenous antibiotics, antiviral drugs, or antifungal drugs.
16. History of (non-infectious) ILD/pneumonia requiring steroids, currently having ILD/pneumonia, or unable to exclude suspected ILD/pneumonia on imaging during screening.
17. Pulmonary criteria:
18. Clinically significant pulmonary comorbidities, including but not limited to any underlying pulmonary disease (e.g., pulmonary embolism, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc.) within 3 months of study recruitment.
19. Any autoimmune disease, connective tissue disease, or inflammatory disease (e.g., rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc.) with recorded or suspected pulmonary involvement during screening. All detailed information about the disease should be recorded in the CRF for participants in the study.
20. Previous total pneumonectomy.
21. Allergic constitution, or known history of allergy to any component of the study regimen, or allergic to other monoclonal antibodies.
22. History of gastrointestinal bleeding within the past 6 months or a clear tendency for gastrointestinal bleeding, such as: esophageal varices at risk of bleeding, local active ulcer lesions, fecal occult blood ≥ (++) not eligible for enrollment; if fecal occult blood (+), gastroscopy is required;
23. Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days before participating in this study;
24. Urinalysis shows urine protein ≥++ or confirmed 24-hour urine protein quantitative \>1.0g;
25. Hypertension, and blood pressure cannot be lowered to the normal range with antihypertensive drugs (systolic blood pressure \>140mmHg, diastolic blood pressure \>90mmHg).
26. Substance abuse or medical conditions that the researcher believes may interfere with the subject's participation in the clinical study or the assessment of the clinical study results.