This study evaluates the addition melatonin and metformin to conventional chemotherapy FDC (Fluoruracil, Doxorubicin, cyclophosphamide) in the treatment of locally advanced breast cancer. Third of patients will receive FDCх6 cycles, other third will receive combination of melatonin and FDCх6 cycles and other patients will receive combination of metformin and FDCх6 cycles.

The treatment of locally advanced breast cancer is a complicated issue. For neoadjuvant treatment is often needed to downstage locally advanced BC tumors prior to surgery, however many patients do not achieved objective response during treatment. The ability of melatonin and metformin to decrease side effects of chemotherapy had been investigated, moreover several studies confirm, that this drugs in combination with conventional treatment may increase objective response. But, this data is still controversial. We hypothesized that combinations of melatonin and conventional chemotherapy regimen such as FDC could be more effective than FDC alone in terms of response rate.

Inclusion Criteria:

• Age >18. Obtained Inform Consent Morphologically confirmed breast cancer stage IIB, IIIA,IIIB,IIIC. ( triple negative, luminal B) Eastern Collaborative Oncology Group Performance Status Scale 0 - 2. Expected survival >6 month Adequate liver and bone marrow function

Exclusion Criteria:

• Systemic treatment for breast cancer IV stage disease Evidence of liver and bone marrow clinically meaningful disfunction Severe uncontrolled concomitant conditions and diseases Pregnancy or lactation Second malignancy Diabetes mellitus requiring drug therapy Any condition preventing study participation by investigator opinion