A Phase II Study of SHR-A1811 Combined With Radiotherapy in HER2-positive and HER2-low Breast Cancer Brain Metastases

Inclusion Criteria: 1. Pathologically confirmed HER2 positive (IHC 3+ or IHC 2+/FISH+)or HER2-low(IHC1+ or 2+/FISH-) advanced breast cancer 2. Age\>18 years. 3. newly diagnosed Brain metastases confirmed by enhanced brain MRI. Metastases number less than 6. 4. No more than four lines of previous advanced therapy 5. Life expectancy of more than 3 months 6. There were no known or suspected leptomeningeal brain metastases 7. The interval from previous therapy was more than 2 weeks, and acute toxicity from previous therapy had to resolve to grade 1 or less 8. The use of mannitol, bevacizumab, or hormone therapy was allowed before enrollment, but the dose was stable for at least a week without the need for an increment 9. Screening laboratory values must meet the following criteria( and should be obtained within 28 days prior to registration): Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets≥ 90 x 109/L, Hemoglobin ≥ 90 g/L Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 x ULN without liver metastasis,≤ 5 x ULN with liver metastases Serum BUN and creatinine ≤ 1.5 x Upper Limit of Normal (ULN) LVEF ≥ 50% QTcF \< 480 ms INR≤1.5×ULN，APTT≤1.5×ULN 10.Signed the informed consent form prior to patient entry Exclusion Criteria: 1. Leptomeningeal or hemorrhagic metastases 2. previously used T-dxd 3. Uncontrolled epilepsy 4. Severe or uncontrolled disease: severe cardiovascular disease, end-stage renal disease, severe hepatic disease, history of immunodeficiency, including HIV positive, active HBV/HCV or other acquired congenital immunodeficiency disease, or organ transplantation history, active infection, etc. 5. History of allergy to treatment regimens 6. Pregnancy or lactation period， women of child-bearing age who are unwilling to accept contraceptive measures. 7. Inability to complete enhanced MRI 8. Not suitable for inclusion for specific reasons judged by sponsor -