Myocet + Cyclophosphamide + Metformin Vs Myocet + Cyclophosphamide in 1st Line Treatment of HER2 Neg. Metastatic Breast Cancer Patients

Inclusion Criteria: 1. Patients must have histologically or cytologically confirmed breast cancer 2. Metastatic disease 3. HER2 negative disease, as measured by IHC or FISH 4. Non endocrine responsive disease (negative hormonal status or failure of endocrine therapy for MBC) 5. Patients with measurable and/or non-measurable disease according to RECIST Criteria (Version 1.1) 6. Homa Index calculated according to Matthews' formula 7. Prior endocrine therapy is allowed, in the adjuvant and/or metastatic setting 8. Prior chemotherapy is allowed, only in adjuvant setting, provided it is terminated at least 12 months before study entry. Adjuvant anthracyclines are allowed if prior cumulative dose does not exceed 360 mg/m2 in case of epirubicin and 280 mg/m2 in case of doxorubicin. Adjuvant taxanes are allowed. 9. Age 18-75 years 10. Life expectancy of greater than 3 months 11. ECOG performance status \<2 12. Patients must have normal organ and marrow function: * leukocytes \>=3,000/μL * absolute neutrophil count \>=1,500/μL * platelets \>=100,000/μL * total bilirubin within normal institutional limits * AST(SGOT)/ALT(SGPT) \<=1.5 X institutional upper limit of normal * creatinine within normal institutional limits 13. Adequate cardiac function, i.e. left ventricular ejection fraction (LVEF)\>= 50% 14. The effects of liposomal doxorubicin on the developing human fetus at the recommended therapeutic dose are unknown. For this reason and because anthracyclines as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. All women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to the start of study medication. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately. 15. Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: 1. Known diabetes (type 1 or 2) 2. Currently on metformin, sulfonylureas, thiazolidenediones or insulin for any reason (these drugs alter insulin levels) 3. Current or previous congestive heart failure, renal failure or liver failure; history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day 4. Creatinine above upper limit of normal for institution, AST above 1.5 times upper limit or normal for institution (to reduce risk of lactic acidosis) 5. Hypersensitivity or allergy to metformin 6. Participation in another clinical trial with any investigational agents within 30 days prior to study screening 7. Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events 8. History of allergic reactions attributed to compounds of similar chemical or biologic composition to Myocet or other agents used in the study 9. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.