Pyrotinib as a novel irreversible tyrosine kinase inhibitor for locally advanced human epidermal growth factor receptor 2-positive breast cancer

INTERVENTION: It will be performed in the First Hospital of China Medical University, Shengjing Hospital of China Medical University, The Fourth Affiliated Hospital of China Medical University, Liaoning Cancer Hospital/Institute, Affiliated Zhongshan Hospital of Dalian University, The Second Hospital of Dalian Medical University, China. A total of 532 HER2‐positive breast cancer will be included in this study. Eligible subjects will be allocated to a trial group and a control group at a 1:1 ratio using the stratified block randomization. In the trial and control group group, treatment with pyrotinib, trastuzumab, docetaxel, and carboplatin in combination and treatment with trastuzumab, docetaxel, and carboplatin in combination will be performed separately in each 21‐day session of treatment. After six treatment sessions, subjects with surgical indications may undergo breast‐conserving surgery or mastectomy according to applicable routine clinical practice. The primary outcome measure of this study is total pathologic complete response (tpCR). Secondary outcome measures are objective response rate (ORR), Eastern Cooperative Oncology Group (ECOG) performance status score, routine blood test, blood biochemical indicators, and routine urine test. Both study and control groups will receive treatment with trastuzumab, docetaxel, and carboplatin in combination. (1)Trastuzumab (Herceptin®, imported drug registration certificate No. S20110007, Shanghai Roche Pharmaceutical Co., Ltd.) will be intravenously administered on the 1st day of each treatment session. There will be four 21‐day sessions of treatment (1‐4 sessions of treatment). The subjects will receive 8 mg/kg trastuzumab in the first session and 6 mg/kg trastuzumab in the second to fourth sessions. (2)Docetaxel (Aventis Pharma, license No. H20140944) will be intravenously administered once every 3 weeks at a dose of 75 mg/m2. There will be six 21‐da CONDITION: Breast cancer ; Cancer ; Breast cancer PRIMARY OUTCOME: ; Total pathologic complete response (tpCR) rate. Hematoxylin‐eosin staining will be performed to observe the presence of residual invasive carcinoma in the surgical sections. If there is no residual invasive carcinoma (ypT0/isypN0), it will be regarded as total pathologic complete response.; tpCR rate is the percentage of total number of patients having total pathologic complete response among total number of patients.; SECONDARY OUTCOME: ; 1. Objective response rate (ORR): It is defined as the proportion of subjects who achieve a complete response (CR) or partial response (PR) during receiving neoadjuvant therapy. ORR will be assessed according to RECIST v1.1 guideline.; 2. Eastern Cooperative Oncology Group (ECOG) performance status score: It is a 5‐point measure indicating a subject’s general health status and treatment tolerance. Higher points indicate poor performance status. ECOG performance status will be evaluated on the 1st day of each treatment session and before surgery.; 3. Routine blood test: Hemoglobin level, red blood cell, platelet count, white blood cell, and neutrophil counts will be determined before administration on the 1st day of each treatment session (or within 3 days before administration) and before surgery.; 4. Biochemical indicators: blood levels of sodium, potassium, chlorine, calcium, magnesium, cholesterol, triglyceride, glucose, urea nitrogen or urea, creatinine, total protein, albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma‐glutamyltransferase, total bilirubin, and direct bilirubin will be measured before administration on the 1st day of each treatment session (or within 3 days before administration) and before surgery.; 5. Routine urine test: Protein, glucose, and blood in urine will be measured before surgery. If the urine protein is tested positive (two or more ++), a 24‐hour urine protein test will be performed.; INCLUSION CRITERIA: 1. Female breast cancer patients at the age of = 18 years and = 65 years who received first treatment 2. ECOG (Eastern Cooperative Oncology Group) score of 0 or 1 3. Histologically confirmed invasive breast cancer with a primary tumor diameter of more than 2 cm; TNM staging T2‐3, N2 or N3, M0 4. Pathologically confirmed HER2‐positive breast cancer, which is defined as the immunohistochemistry score of > 10% immunoreactive cells being 3+ or in situ hybridization results showing HER2 gene amplification 5. Known state of hormone receptors and progesterone receptor is known 6. The functional level of the main organs must meet the following requirements (no blood transfusion and no use of leukocytes‐ and platelets‐raising drugs in 2 weeks before screening): absolute neutrophil count (ANC) = 1.5 × 109/L, platelet (PLT) count = 90 × 109/L, hemoglobin (Hb) =