Preoperative letrozole versus letrozole with metformin in postmenopausal Estrogen receptor positive breast cancer patients

Phase II multicenter 1:1 randomized clinical trial Total 208 patients

Primary endpoint Clinical response rate

Secondary endpoint Pathologic complete response rate Breast conserving surgery rate Percent mammographic density change Ki67(%) change after 4week medication of 2nd core needle biopsy Toxicity profile of neoadjuvant letrozole, metformin

To identify the anti-tumor effect of metformin with preoperatively given letrozole in postmenopausal estrogen receptor positive breast cancer patients

Inclusion Criteria:

• Estrogen receptor positive breast cancer
• Clinically measurable tumor size(stage II/III)
• No evidence of distant metastasis
• Postmenopause women 'Age≥60yr' OR 'previous bilateral oophorectomy' OR 'FSH>30 with no bleeding history within 1yr'
• ECOG 0-2
• Adequate hepatorenal, bone marrow function 'serum Cr<1.4mg/dL' AND 'Bilirubin< upper limit of normal x 1.5 AND 'AST/ALT < upper limit of normal x 1.8 AND 'ALP < upper limit of normal x 1.8 AND 'Hemoglobin >10 g/dL' AND 'ANC >1,500/mm3' AND 'Platelet >100,000/mm3'
• Spontaneous signed into the written informed consent

Exclusion Criteria:

• Who does not meet the above inclusion criteria
• History of other carcinoma
• Uncontrolled infection
• History of psychiatric, epileptic disease
• Male breast cancer
• Diabetes 'HbA1c≥6.5' OR 'FBS≥126mg/dL'
• Hypersensitivity or intolerance to metformin
• Risk of metformin associated lactic acidosis 'Congestive heart disease of NYHA Class llll/IV' OR 'History of other acidosis' OR 'Alcohol intake more than either 3 bottles beer OR 1 bottle Soju'
• During medication of metformin, sulfonylureas, thiazolidinediones, insulin
• Diffuse microcalcification in mammogram
• Multiple OR bilateral OR inflammatory breast cancer
• Chemotherapy or endocrine therapy within 2yr due to history of breast cancer