NeoMET Study in Neoadjuvant Treatment of Breast Cancer

• women aged ≥18 years and \< 70 years with life expectancy > 12 months
• Measurable disease in breast or axillary lymph node, histologically confirmed invasive breast cancer by core needle biopsy, T≥2cm or stage IIb or stage III according AJCC classification, fine-needle aspiration is encouraged to every patient with metastasis suspicious nodes;
• Biopsy specimens are available for ER, PgR, Her2 and proliferation biomarker detection;
• Adequate bone marrow function: Neutrophil ≥ 1.5*109/L; Hb ≥ 100g/L; PLT ≥ 80*109/L;
• Adequate liver and renal function:
• Serum AST ≤ 90U/L
• Bilirubin ≤ upper limit of normal (UNL) range
• Serum creatinine ≤110 umol/L，calculated creatinine clearance should be ≥ 60 mL/min;
• BUN ≤ 7.1mmol/L;
• Has ECOG Performance Score 0-1;
• BMI ≥ 25kg/m2 or hyperglycemia or hyperlipemia or hypertension;
• Willing to take biopsy before neoadjuvant chemotherapy and patients must be accessible for treatment and follow-up;
• Women with potential child-bearing must have a negative pregnancy test (urine or serum) within 7 days of drug administration and agree to use an acceptable method of birth control to avoid pregnancy for the duration of the study;
• Written informed consent according to the local ethics committee requirements.

Exclusion Criteria:

• Prior systemic or loco-regional treatment of breast cancer, including chemotherapy;
• Metastatic breast cancer;
• With a history of malignant tumor except uterine cervix cancer in situ or skin basal cell carcinoma;
• Patients with medical conditions that indicate intolerant to neoadjuvant therapy and related treatment, including uncontrolled pulmonary disease, severe infection, active peptic ulcer, coagulation disorder, connective tissue disease or myelo-suppressive disease;
• Has active hepatitis B or hepatitis C with abnormal liver function tests (LFTs) or is known to be HIV positive;
• Contraindication for using dexamethasone, chemotherapy agents or metformin;
• History of congestive heart failure, uncontrolled or symptomatic angina pectoris, arrhythmia or myocardial infarction; poorly controlled hypertension (systolic BP >180mmHg or diastolic BP >100mmHg);
• Has peripheral neuropathy ≥ grade 1;
• Patient is pregnant or breast feeding (not willing to stop breast feeding);
• Not willing to take core needle biopsy or patients with psychiatric disorder or other diseases leading to incompliance to the therapy
• Known severe hypersensitivity to any drugs in this study;
• Treatment with any investigational drugs within 30 days before the beginning of study treatment.
• History of lactic or other metabolic acidosis
• Consumption of > 3 alcoholic beverages per day (on average)