Trastuzumab Rezetecan vs Trastuzumab Deruxtecan in the Neoadjuvant Treatment of HER2 Positive Breast Cancer

Inclusion criteria

• 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)
• Negative pregnancy test (childbearing women); agree to effective contraception
• Sign an informed consent form.

Exclusion criteria

• 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).
• Live/attenuated vaccine (past 4 weeks); major non-breast surgery (4 weeks prior, incomplete recovery).
• Active/relapsing autoimmune disease (except controlled hypothyroidism/well-managed skin diseases/type 1 diabetes); immunodeficiency (HIV+/organ transplant).
• Uncontrolled cardiovascular/cerebrovascular disease (e.g., MI/stroke in 6 months, NYHA III-IV heart failure, QTcF >470 msec [female]).
• Active ILD/severe lung disease; active hepatitis B (HBsAg+ & HBV DNA ≥500 IU/mL)/hepatitis C (HCV RNA+); severe infection requiring anti-infective therapy.
• Bleeding/thrombotic tendency; hypersensitivity to study drugs/excipients.
• Pregnant/lactating women; women of childbearing potential with positive pregnancy test or refusing contraception.
• Other conditions (e.g., uncontrolled hypertension/diabetes, neuropsychiatric disorders) deemed unsuitable by the investigator.