Metformin, a drug that has been used since the 1950's in the treatment of diabetes, has
recently generated great interest in its anticancer effects based on in vitro, in vivo and
clinical studies. This study assesses the pharmacodynamic effects of metformin on breast
cancer metabolism.
The trial design is based on a 2 centre study 'Early Antiangiogenic Response to Bevacizumab
in Primary Breast Cancer' that is about to successfully complete recruitment in Oxford and
Mount Vernon hospitals. The study takes advantage of the 2 week window between the first
clinic visit and commencement of neoadjuvant chemotherapy. Metformin will be given to
patients for at least 2 weeks prior to neoadjuvant chemotherapy with a set of 3 breast core
biopsies, a PET-CT scan and blood tests carried out before and after this 2 week period of
treatment. Patients will also receive a drink of heavy (deuterated) water, a safe and stable
isotope commonly used in clinical lipid metabolism studies, the evening prior to both sets of
core biopsies. Having completed the first 2 weeks of metformin patients will have the option
of continuing metformin until completion of chemotherapy, at the discretion of the trial
physician.
The core biopsies will then be used to assess for changes in:
- immunohistochemical staining;
- gene profiles;
- uptake of heavy water into tumour fatty acids using mass spectrometry techniques.
The aim is to identify potential biomarkers of response to metformin (and other future cancer
metabolism drugs).