The purpose of this study is to evaluate the safety, effectiveness and cost-effectiveness of metronomic chemotherapy combined with trastuzumab as neoadjuvant therapy for locally advanced HER2-positive breast cancer.

Inclusion Criteria:

• Diagnosis of locally advanced breast cancer
• T > 2 cm (any N), or any T and positive node(needle biopsy is required if tumor size is less than 2cm)
• Non-metastatic disease confirmed by computerized tomography and bone scan
• HER2 positive by IHC (+++) and/or Fish (+) according to international definitions (ASCO 2007)
• Normal left ventricular ejection fraction (LVEF)
• Indication of preoperative chemotherapy
• multifocal tumors acceptable provided that the largest tumor is Her2-positive
• ECOG 0-1

Exclusion Criteria:

• Another malignancy within the last 5 years (except curatively treated skin carcinoma, in situ cervix carcinoma, in situ ductal carcinoma of the breast, or in situ lobular carcinoma of the breast)
• Clinically significant comorbidities such as cardiovascular diseases, COPD, renal or liver impairment, psychiatric disorders
• LVEF value below institutional limits of normal range
• Detected or suspected distant metastasis
• Neutrophils lower than 1,500/µL, platelets lower than 100,000/µL, hemoglobin lower than 10 g/dL, AST higher than 2.5x upper limit of normal (ULN), total bilirubin higher than ULN, alkaline phosphatase more than 1.5x ULN