This is a single-center, randomized, open-label, phase II interventional study. Eligible patients will be randomized 1:1 to receive either Trastuzumab-rezetecan (4.8 mg/kg Q3W) or T-DXd (5.4 mg/kg Q3W) for 8 neoadjuvant cycles. After completing neoadjuvant treatment, patients will undergo definitive surgery, and tpCR will be assessed from resected specimens. Patients will then be followed up to monitor long-term efficacy (e.g., EFS) and late-onset adverse events. A total of 68 patients (34 per arm) will be enrolled to achieve the study's statistical objectives.
Female, 18-75 years old, treatment-naive
ECOG PS 0-1
Histologically confirmed HER2+ (IHC 3+ or IHC 2+/ISH+) early/locally advanced breast cancer (AJCC 8th: cT2-cT4 any N cM0) or cT1c N+ cM0; known ER/PR status
Adequate organ function (hematology/biochemistry/coagulation/urine/cardiac)
Bbilateral/inflammatory/occult breast cancer.
Prior anti-tumor therapy (chemotherapy/radiotherapy/targeted therapy, etc.); radical radiotherapy (4 weeks prior) or palliative radiotherapy (2 weeks prior) to first dose.
Concurrent anti-tumor therapy; other malignancies (within past 5 years, except cured basal cell carcinoma/cervical CIS).
Prior trial participation (past 4 weeks); systemic immunosuppressants/hormones (>10 mg/day prednisone equivalent, 2 weeks prior; nasal/inhaled steroids excluded).