Neoadjuvant Trastuzumab-rezetecan Plus Pertuzumab or Nab-Paclitaxel, Carboplatin, Trastuzumab, and Pyrotinib After Suboptimal Response to Neoadjuvant Dual HER2-Targeted Therapy Combined With Chemotherapy in HER2-Positive Early Breast Cancer

Inclusion criteria

• Age ≥18 and ≤75 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• Primary tumor size \>1 cm.
• Histologically confirmed invasive breast cancer, clinically staged as:
• Stage I (T1cN0M0)
• Stage II (T1cN1M0, T2N0-1M0 or T3N0M0)
• Stage III (T2N2-3M0, T3N1-3M0, or T4N0-3M0)
• HER2-positive status: IHC 3+ or IHC 2+ with positive ISH.
• Adequate major organ function:
• Hematology (no transfusion or hematopoietic growth factors, e.g., G-CSF, within 14 days):
• Hemoglobin ≥100 g/L
• Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L
• Platelet count ≥100 × 10⁹/L
• Biochemistry:
• Total bilirubin ≤1.5 × ULN
• ALT and AST ≤1.5 × ULN; ALP ≤2.5 × ULN
• BUN and creatinine ≤1.5 × ULN
• Cardiac function: LVEF ≥55% by echocardiography
• Women of childbearing potential must have a negative pregnancy test within 7 days prior to enrollment and agree to use effective contraception during the study and for 8 weeks after the last dose.
• Voluntary written informed consent and willingness to comply with study procedures and follow-up.

Exclusion criteria

• Prior anti-tumor therapy for breast cancer, including chemotherapy, radiotherapy, targeted therapy, or endocrine therapy.
• Concurrent administration of any other anti-tumor treatment.
• Bilateral breast cancer, inflammatory breast cancer, or occult breast cancer.
• Breast cancer not confirmed histologically.
• History of other malignancy within the past 5 years, except successfully treated cervical carcinoma in situ.
• Severe dysfunction of major organs (heart, liver, kidney).
• Conditions affecting oral drug administration or absorption, e.g., inability to swallow, chronic diarrhea, or intestinal obstruction.
• Participation in another investigational drug trial within 4 weeks prior to enrollment.
• Known hypersensitivity to study drug components; history of immunodeficiency (HIV positive, active HCV, active hepatitis B, other congenital/acquired immunodeficiency) or prior organ transplantation.
• History of clinically significant cardiac disease, including:
• Arrhythmia requiring medication
• Myocardial infarction
• Heart failure
• Other cardiac conditions deemed unsuitable for study participation by the investigator
• Pregnant or breastfeeding women, or women of childbearing potential who test positive at baseline or are unwilling to use effective contraception throughout the study.
• Any condition that, in the investigator's judgment, poses serious risk to patient safety or may interfere with study completion (e.g., uncontrolled severe hypertension, uncontrolled diabetes, active infection).
• History of neurological or psychiatric disorders (e.g., epilepsy or dementia) or any other condition the investigator considers incompatible with study participation.