Neoadjuvant Oral Paclitaxel Plus Subcutaneous Pertuzumab/Trastuzumab in Patients With HER2-positive Breast Cancer

Inclusion criteria

• Aged 18-75 years old. Histologically confirmed HER2-positive invasive breast cancer with clinical stages T1c-4, N0-3, and M0 (excluding T1cN0M0), according to the 8th American Joint Committee on Cancer (AJCC) edition BC staging system HER2 overexpression was defined as immunohistochemistry (IHC) 3+ or 2+ with HER2 gene amplification, determined by fluorescence in situ hybridization (FISH).
• Baseline left ventricular ejection fraction (LVEF) of ≥50%. Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1.
• The functional level of major organs must meet the following requirements (no blood transfusion and no use of white blood cell, red blood cell and platelet-raising drugs within 2 weeks before the first dose):
• Absolute neutrophil count ≥ 1,500/mcL
• Platelets ≥ 100,000/mcL
• Hemoglobin ≥ 9.0 g/dL
• Total bilirubin ≤ 1.5 x upper limit of normal (ULN)
• Alanine aminotransferase and aspartate aminotransferase (ALT/AST) ≤1.5×ULN
• Blood urea nitrogen and serum creatinine ≤1.5×ULN
• Creatinine clearance (Ccr) ≥50 ml/min (Cockcroft-Gault formula) Signature of informed consent

Exclusion criteria

• History of invasive breast cancer. Bilateral breast cancer or inflammatory breast cancer . Prior excisional and/or incisional biopsy of the primary tumor and/or axillary lymph nodes.
• Prior systemic therapy for breast cancer. History of life-threatening hypersensitivity reactions or known hypersensitivity to any component of the investigational drug.
• Participation in another clinical trial of a drug or medical device within 4 weeks prior to the first dose and/or receipt of investigational drug/device during the trial.
• Major surgery within 28 days prior to the first dose or planned major surgery during the study period.
• History of other malignancies within the past 5 years, except for carcinoma in situ of the cervix, non-melanoma skin cancer, localized prostate cancer, or ductal carcinoma in situ.
• Active tuberculosis or other severe infectious diseases requiring systemic treatment, including but not limited to bacteremia, severe pneumonia, and other serious infections.
• History of immunodeficiency or autoimmune diseases, including but not limited to HIV infection (HIV antibody positive), systemic lupus erythematosus, rheumatoid arthritis, or history of organ transplantation.
• History of cardiovascular or cerebrovascular diseases, including:
• Unstable angina;
• Clinically significant arrhythmias requiring medication;
• Myocardial infarction within the past 6 months;
• Heart failure or second-degree or higher atrioventricular block;
• Cerebral infarction (excluding lacunar infarction) or cerebral hemorrhage within the past 6 months.
• Poorly controlled hypertension (systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg despite regular medication), or history of hypertensive crisis or hypertensive encephalopathy.
• Unsuitability for oral administration of the investigational drug, as judged by the investigator, including:
• Clinically significant or uncontrolled congenital or acquired gastrointestinal diseases;
• Diseases that may affect drug administration, gastric entry, or absorption (e.g., intestinal obstruction, Crohn's disease, ulcerative colitis).
• Pregnant or breastfeeding women; women of childbearing potential with a positive pregnancy test at screening; or those unwilling to use effective contraception during the study and for 6 months after the last dose.