This research study will evaluate the efficacy and safety of stereotactic radiotherapy (SRT) combined with Trastuzumab-Deruxtecan (T-DXd; DS-8201a) in HER2-positive Breast Cancer Patients with newly diagnosed or progressing Brain Metastases.

Inclusion Criteria:

• Pathologically confirmed HER2 positive advanced breast cancer

• Age>18 years.

• Brain metastases confirmed by enhanced brain MRI. Metastases number less than 15.

• KPS≥70 or KPS ≥60 with neurologic symptoms caused by BM

• Life expectancy of more than 6 months

• Prior therapy of oral dexamethasone not exceeding 16mg/d

• Time interval from prior therapy was more than 2 weeks, and evaluation of adverse events is no more than grade 1.

• Screening laboratory values must meet the following criteria( and should be obtained within 28 days prior to registration):

  1. Absolute Neutrophil Count (ANC) ≥ 1.5 x 109/L, Platelets≥ 90 x 109/L, Hemoglobin ≥ 90 g/L
  2. Aspartate aminotransferase/alanine aminotransferase (AST/ALT) ≤2.5 x ULN without liver metastasis,≤ 5 x ULN with liver metastases
  3. Serum BUN and creatinine ≤ 1.5 x Upper Limit of Normal (ULN)
  4. LVEF ≥ 50%
  5. QTcF < 480 ms
  6. INR≤1.5×ULN，APTT≤1.5×ULN

• Signed the informed consent form prior to patient entry

Exclusion Criteria:

• Leptomeningeal or hemorrhagic metastases
• Uncontrolled epilepsy
• 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.
• History of allergy to treatment regimens
• Pregnancy or lactation period， women of child-bearing age who are unwilling to accept contraceptive measures.
• Inability to complete enhanced MRI
• Not suitable for inclusion for specific reasons judged by sponsor