Effect of Metformin on Breast Cancer Metabolism

Metformin is a safe and well tolerated drug that has been widely used in the treatment of diabetes for over 50 years. There is now growing evidence from in vitro laboratory and animal work that metformin has anticancer properties. In addition a retrospective clinical study in a diabetic population has demonstrated evidence of markedly increased pathological response rates (a typically robust surrogate clinical endpoint of efficacy) to pre-surgical chemotherapy in early breast cancer for patients that were also taking metformin as part of their diabetes treatment.

There are several studies of metformin in cancer patients ongoing or being developed worldwide These are predominantly in relatively unselected cancer populations and with clinical outcomes as endpoints. However this study is the only study currently planned which will carry out a substantial assessment of pharmacodynamic endpoints. It is important that this study is carried out at an early stage in the development of metformin as a potential cancer therapy in order to ensure that future large scale studies are properly informed.

Inclusion criteria

• Women with histology proven locally advanced breast cancer (LABC) or tumours >3 cm in diameter.
• ECOG performance status 0-1.
• Age ≥18 years.
• No prior treatment for breast cancer and scheduled to commence neoadjuvant chemotherapy in <3 weeks time.
• Have given written informed consent and are capable of cooperating with protocol.
• Adequate bone marrow, renal and liver function.

Exclusion criteria

• Radiotherapy, major surgery, significant traumatic injury, endocrine therapy, immunotherapy, chemotherapy or experimental therapy during four weeks prior to starting or during trial.
• Pregnancy or breast feeding
• History of type 1 or type 2 diabetes.
• Serum glucose greater than 7.0 mMol/L.
• Treatment with metformin in the past year.
• Estimated glomerular filtration rate (eGFR) <45ml/min.
• Acute or chronic metabolic acidosis
• Known hypersensitivity to metformin
• Other psychological, social or medical condition, physical examination finding or a laboratory abnormality that the Investigator considers would make the patient a poor trial candidate or could interfere with protocol compliance or the interpretation of trial results.