Neoadjuvant Therapy With Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab or Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab Sequenced With Paclitaxel-based Regimens + Trastuzumab + Pyrotinib in HER2+ Breast Cancer
Patients with Stage II-III HER2-positive breast cancer will receive three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by imaging assessment. If clinical complete response (cCR) or radiological complete response/near radiological complete response (rCR/near rCR) is achieved, they will continue to receive an additional three cycles of treatment with Trastuzumab Deruxtecan (SHR-A1811) + Pertuzumab, followed by surgery. If cCR/rCR or near rCR is not achieved, the treatment will be switched to the THPy regimen (paclitaxel-based regimen + Trastuzumab + Pyrotinib) for three cycles.
• Age and Gender: Female patients aged ≥18 years and ≤70 years. Histological Confirmation: Patients must have histologically confirmed invasive breast cancer and must not have received any prior systemic anti-tumor therapy for breast cancer.
• HER2 Positivity: Histologically confirmed HER2 receptor positivity, following the 2018 ASCO-CAP HER2 positivity judgment guidelines.
∙ Confirmed by pathology laboratory with immunohistochemistry (IHC) score of 3+, or 2+ with positive in situ hybridization (ISH) test (ISH amplification rate ≥2.0).
• Tumor Stage: Patients must have tumor staging conforming to the Stage II-III breast cancer criteria according to the eighth edition of the AJCC breast cancer TNM staging system (T1\
∙ T4, N1\
∙ N3, M0).
• Measurable Target Lesion: At least one measurable target lesion according to RECIST V1.1.
• ECOG Performance Status: ECOG functional status score of 0\
• Organ Function: Adequate organ function levels, with the following requirements (no blood transfusion or use of leukocyte or platelet elevation drugs within 2 weeks prior to screening):
‣ Hematology: Absolute neutrophil count (ANC) \> 1.5 × 109/L; Platelet count (PLT) \> 75 × 109/L; Hemoglobin (Hb) \> 90 g/L.
⁃ Blood Chemistry: Total bilirubin (TBIL) \< 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 1.5 × ULN; Alkaline phosphatase \< 2.5 × ULN; Blood urea nitrogen/urea (BUN/UREA) and creatinine (Cr) \< 1.5 × ULN.
⁃ Cardiac Ultrasound: Left ventricular ejection fraction (LVEF) ≥ 55%.
⁃ 12-Lead ECG: Fridericia's method corrected QT interval (QTcF) \< 470 msec.
• Reproductive Status: For premenopausal women with potential fertility, a pregnancy test must be performed within 7 days before treatment initiation, with negative serum/urine pregnancy results.
• Patients must not be lactating and must use adequate barrier contraception throughout the treatment cycle and for 6 months after treatment completion.
∙ Voluntary Participation: Voluntary participation in the study with signed informed consent, good compliance, and willingness to cooperate with visit schedules and research-related procedures.