Trastuzumab Rezetecan Neoadjuvant Therapy in THP-Insensitive HER2-Positive Early Breast Cancer

Inclusion criteria

• 1.Age ≥18 years. For premenopausal and perimenopausal patients, a negative pregnancy test is required, and the patient must agree to use effective contraception during treatment.
• 2.Pathologically confirmed invasive breast cancer, stage II-III according to the 8th edition of the American Joint Committee on Cancer (AJCC) TNM staging system, with HER2-positive disease defined as: immunohistochemistry (IHC) 3+; or IHC 2+ with confirmed HER2 gene amplification by fluorescence in situ hybridization (FISH).
• 3.At least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1.
• 4.No prior chemotherapy, immunotherapy, endocrine therapy, radical surgery, or radiotherapy for breast cancer.
• 5.Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• 6.Ability to understand and provide written informed consent.
• 7.Adequate organ function as evidenced by the following laboratory values:
• Hemoglobin ≥90 g/L
• White blood cell count ≥3.5×10⁹/L
• Platelet count ≥100×10⁹/L
• Neutrophil count ≥1.5×10⁹/L
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤3× upper limit of normal (ULN)
• Total bilirubin ≤1.5×ULN
• Serum creatinine ≤1.5×ULN
• 8.No evidence of myocardial ischemia on electrocardiogram (ECG); New York Heart Association (NYHA) functional class I; left ventricular ejection fraction (LVEF) ≥55% on echocardiogram; cardiac biomarkers (cardiac troponin I [cTnI] and B-type natriuretic peptide [BNP]) within normal limits.
• 9.All required baseline laboratory and radiologic examinations completed prior to neoadjuvant therapy.
• 10.No dysphagia.
• 11.Availability of complete clinical data.

Exclusion criteria

• 1.Male breast cancer or inflammatory breast cancer.
• 2.Metastatic breast cancer (Stage IV).
• 3.Presence of other concurrent malignancies or history of malignancy other than breast cancer within the past 5 years, except for adequately treated basal cell carcinoma, squamous cell carcinoma of the skin, or carcinoma in situ of the cervix.
• 4.Receipt of any other concurrent anti-cancer therapy or participation in another clinical trial.
• 5.Presence of severe non-malignant disease that would compromise patient compliance or place the patient at unacceptable risk.
• 6.Major surgical procedure within 4 weeks prior to initiation of study treatment, or anticipated need for major surgery during the study period.
• 7.Receipt of radiotherapy, chemotherapy, molecular targeted therapy, endocrine therapy, or major breast surgery for breast cancer within 4 weeks prior to study treatment; current or prior use of HER2-targeted monoclonal antibodies, HER2-targeted antibody-drug conjugates (ADCs), or tyrosine kinase inhibitors (TKIs).
• 8.History of hypersensitivity or contraindication to any component of the study drugs.
• 9.Poorly controlled cardiac symptoms or diseases, including: New York Heart Association (NYHA) Class II or higher heart failure; unstable angina; myocardial infarction within 1 year; clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention.

Dementia, intellectual disability, or any psychiatric disorder that impairs the ability to understand the informed consent form.