Trastuzumab Combined With Pertuzumab for Adjuvant Treatment of Breast Cancer After Neoadjuvant Therapy

Inclusion Criteria:

• Female patients aged ≥ 18 but ≤ 75 years (The maximal age of the subjects enrolled inthe Phase 3 study of pyrotinib is 75 years old, and there is no safety data for theuse of the drug in older people);
• ECOG level 0-1;
• Primary infiltrating breast lesions and lymph nodes should follow these conditions atthe same time: histologically confirmed invasive breast cancer; receiving neoadjuvanttreatment and completing the operation, with postoperative pathological examinationindicating residual invasive cancer in the breast or axillary lymph nodes;HER2-positive breast cancer is confirmed in the pathology test, with 3+ inimmunohistochemistry (IHC) test and HER2 gene amplification (HER2/CEP17 ≥ 2.0 oraverage HER2 copy number/cell number ≥ 6); no recurrent and metastatic disease aftersurgery;
• HER-2 positive breast cancer patients who have non-pCR after trastuzumab+pertuzumab asneoadjuvant therapy, and have completed trastuzumab combined with pertuzumab asadjuvant treatment. During the neoadjuvant and/or adjuvant therapy phase, at least ≥24weeks (8 drug delivery cycles) of trastuzumab + pertuzumab. And the time interval fromthe end of the last trastuzumab treatment to entering the trial must be ≤ 1 year;
• Hormone receptor status (ER and PR) that is known;
• The functional level of major organs must conform to the following requirements (noblood transfusion, no use of white blood cell- and platelet-increasing drugs within 2weeks before screening): Neutrophils (ANC) ≥ 1.5×109/L; Platelet count (PLT) ≥ 90×109/L; Hemoglobin (Hb) ≥ 90 g/L; Total bilirubin (TBIL)≤ 1.5×upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5×ULN;
• Female patients who are not menopausal or not surgically sterilized agree to abstainfrom sex or use effective non-hormonal drugs for contraception during the treatmentperiod and within 8 weeks after the last administration;
• Patients who participate in the trial voluntarily, sign an informed consent, have goodcompliance and are willing to comply with the follow-up visit.

Exclusion Criteria:

• With a history of recurrent local or regional breast disease;
• Stage IV (metastatic) breast cancer;
• Bilateral breast cancer;
• With a history of any malignancies other than breast cancer in the past 5 years,excluding cured cervical carcinoma in situ, skin basal cell carcinoma or squamous cellcarcinoma;
• Patients who have received pyrotinib, lapatinib, neratinib or other tyrosine kinaseinhibitors, enmetrastuzumab (T-DM1), and other anti-tumor biological therapies ortumor immunotherapy;
• Patients who are receiving anti-tumor therapy in other clinical trials, includingendocrine therapy, bisphosphonate therapy or immunotherapy;
• Severe heart disease or discomfort, including but not limited to the followingdiseases: a confirmed history of heart failure or systolic dysfunction (LVEF < 50%);high-risk uncontrolled arrhythmia, such as atrial tachycardia, remarkable ventriculararrhythmia (such as ventricular tachycardia) or higher-grade atrioventricular block;angina pectoris requiring anti-angina medication; clinically significant valvulardisease; transmural myocardial infarction shown by ECG; uncontrolled blood pressure inpatients with hypertension who have been given antihypertensive drugs (systolic bloodpressure > 180 mmHg and/or diastolic blood pressure > 100 mmHg);
• Inability to swallow, intestinal obstruction or other factors that affect drug takingand absorption;
• With a history of diagnosed neurological or mental disorders, including involuntarybehavior or mental illness;
• With a history of gastrointestinal diseases with diarrhea as the main symptom;
• Patients who are known to have a history of allergies to the drug components in thistrial; have a history of immunodeficiency, including HIV positive results, or otheracquired or congenital immunodeficiency diseases; or have a history of organtransplantation;
• Female patients during pregnancy and lactation, or those who are fertile and positivefor baseline pregnancy test;
• Serious concomitant diseases or other comorbid diseases that will interfere with theplanned treatment, including infectious diseases with active infections (including butnot limited to hepatitis B, active hepatitis C, active tuberculosis, active syphilis,etc.); or any other cases in which the investigator believes that the patient cannotparticipate in the trial.