Pyrotinib Plus Capecitabine for Adjuvant Treatment of HER2 Positive Early-stage Breast Cancer

1. Female patients ≥ 18 years and ≤ 75 years old;
2. Primary invasive breast cancer confirmed by histology;
3. HER2 positive breast cancer (IHC 3+, or IHC 2+ and FISH positive); lymph node positive, except for T0; lymph node negative and tumor >1cm, or tumor > 0.5 cm and ≤ 1cm, and accompanied by any of the following high-risk factors: pathological grade 3, ER/PR negative, or \< 35 years old;
4. Having received mastectomy or breast conserving surgery, and received sentinel lymph node biopsy or axillary lymph node dissection, and within 90 days from the breast surgery;
5. With known ER/PR status of breast cancer;
6. ECOG score 0-1;

7. The patient's major organ functions meet all of the following requirements for blood tests:

   1. Neutrophil count (ANC) ≥ 1,500/mm3 (1.5×109/L);
   2. Platelet count (PLT) ≥ 75,000/mm3 (75×109/L);
   3. Hemoglobin (Hb) ≥ 8 g/dL (80 g/L);
   4. Serum creatinine (SCr) ≤ 1.5 times the upper limit of normal (ULN) or creatinine clearance ≥ 60 mL/min;
   5. Total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN);
   6. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) level ≤ 2.5 times the upper limit of normal (ULN), patients with liver metastases should be ≤ 5×ULN.

9. The participant voluntarily joins the study, signs the informed consent form, has good compliance, and cooperates with follow-ups.

Exclusion criteria:

1. Breast cancer recurs before enrollment, or local recurrence/ metastasis confirmed by radiology;
2. The subject has participated in other clinical trials within 4 weeks or 5 half-lives (whichever is longer) before enrollment;
3. The patient has previously received treatment including tyrosine kinase inhibitors targeting HER2 (e.g., lapatinib, neratinib, and pyrotinib);
4. The patient has been diagnosed with other malignancies within 5 years of enrollment, except for cervical carcinoma in situ, basal cell carcinoma of the skin, or squamous cell carcinoma of the skin which has been cured;
5. The patient is receiving anti-tumor therapies from other clinical trials;
6. Inability to swallow, chronic diarrhea, or intestinal obstruction, with multiple factors affecting drug administration and absorption;
7. The patient has undergone major surgical procedures unrelated to breast cancer within 4 weeks of enrollment, or has not fully recovered from such surgical procedures;
8. With known allergies to any components of the agents to be administered in this study; history of acquired or congenital immunodeficiency diseases, including HIV; history of HCV, active hepatitis B, or history of organ transplantation;
9. Pregnant and lactating patients, patients of fertility unwilling to take effective contraceptive measures throughout the trial;
10. With any heart disease including: (1) arrhythmia requiring medication or clinical attention; (2) myocardial infarction; (3) heart failure; (4) any other heart diseases that are considered unsuitable to the trial;
11. With any comorbidities that are considered to potentially endanger the patient's safety or interfere with the study, including but not restricted to resistant hypertension, severe diabetes, active infection, etc.;
12. With a history of neurological or mental disorders, including but not restricted to epilepsy or dementia;
13. The patient is using CYP3A4 inhibitors or inducers, or any other drugs that potentially prolong the QT interval;
14. Any other circumstances in which the researcher believes that the patient is not suitable to participate in this study.