Calorie Restriction With or Without Metformin in Triple Negative Breast Cancer

Exclusion Criteria

• •Patients eligible for this study must not meet any of the following criteria:
• •1. Prior systemic treatment for breast cancer or other malignancies within 5 years of treatment enrollment.
• •2. Prior treatment with anthracyclines
• •3. Diagnosis of other malignancies in advanced stages (unresectable, locally advanced or metastatic), or that required systemic (neo)adjuvant chemotherapy in the previous 5 years. Other malignancies diagnosed more than 5 years before the diagnosis of breast cancer must have been radically treated without evidence of relapse at the moment of patient enrollment in the trial.
• •4. Body mass index (BMI) \< 20 kg/m2.
• •5. History of alcohol abuse.
• •6. Non-intentional weight loss ≥ 5% in the previous 3 months, unless the patient has a BMI \> 22 kg/m2 and weight loss has been lower than 10% at the time of enrollment in the study; or non-intentional weight loss of ≥ 10% in the previous 3 months, unless the patients has a BMI \> 25 kg/m2 and weight loss has been lower than 15% at the time of the enrollment in the study. In both cases, weight must have been stable for at least one month before study enrollment.
• •7. Active pregnancy or breast feeding.
• •8. Known active B or C hepatitis or human immunodeficiency virus (HIV) infection, or occasional finding of active hepatitis B/C infection during screening tests before chemotherapy initiation, as defined as positive polymerase chain reaction (PCR) testing for HBV-DNA and HCV-RNA and qualitative PCR for HIV-RNA, or requiring active treatment at study enrollment.
• •9. Serious infections in the previous 4 weeks before the FMD initiation, including, but not limited to, potential hospitalizations for complications of infections, bacteriemia or serious pneumonitis.
• •10. Active autoimmune diseases requiring systemic treatments (e.g. systemic steroids or immune suppressants).
• •11. Active chronic therapy with systemic steroids at a dose ≥ 10 mg per day of prednisone or equivalent at study enrollment.
• •12. Known recent diagnosis of hypothyroidism requiring systemic replacement hormonal therapy and without stabilization of hormonal profile (fT3, fT4 and TSH within the normal range).
• •13. Diagnosis of type 1 or 2 diabetes mellitus requiring pharmacologic therapy (including, but not limited to, insulin, secretagogues and metformin). A diagnosis of type 2 diabetes mellitus not requiring pharmacological treatments based on the judgment of a diabetologist, is compatible with patient enrollment in the trial.
• •14. Active gastric or intestinal ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small intestine resection.
• •15. Anamnesis of clinically significant heart disease including:
• •1. angina pectoris, coronary bypass, symptomatic pericarditis, myocardial infarction in the previous 12 months from the beginning of experimental therapy;
• •2. congestive heart failure (NYHA III-IV).
• •16. Anamnesis of clinically meaningful cardiac arrhythmias, such as ventricular tachycardia, chronic atrial fibrillation, complete bundle branch block, high grade atrio-ventricular block like bi-fascicular block, type II Mobitz and third grade atrio-ventricular block, nodal arrhythmias, supra-ventricular arrhythmia.
• •17. Left ventricular ejection fraction lower than 50% at the cardiac scan with radionuclides or at echocardiography.
• •18. Previous episodes of symptomatic hypotension leading to loss of consciousness.
• •19. Baseline plasma fasting glucose ≤ 60 mg/dL.
• •20. Medical or psychiatric comorbidities rendering the patient not candidate to the clinical trial, according to the investigator's judgement.