Elias Sundelin, May 2016
Breast cancer is the most common cancer in women worldwide with nearly 1.7 million new cases diagnosed in 2012 (second most common cancer overall). This represents about 12% of all new cancer cases and 25% of all cancers in women. Epidemiological studies have shown that treatment with the antidiabetic drug metformin has a positive outcome on survival in patients with breast cancer. These studies have been followed up by cell and animal studies, which have shown that metformin has antiproliferative effects on breast cancer. The question still remains, whether the effect of metformin on cancer is mediated through an indirect pathway involving inhibition of hepatic glucose production, lowering blood glucose and thereby lowering circulating insulin levels, which act as a tumour growth factor, or the effects are directly on the tumour, involving activation of the energy sensor AMP activated protein kinase (AMPK), which downstream inhibits cell proliferation and cell growth. A direct effect on the tumour requires uptake of metformin in the tumour.
At the PET-centre at Aarhus University Hospital we have developed a unique method to evaluate tissue-specific uptake of metformin in humans with the use of 11C-labelled metformin and PET/CT. With this technique we can investigate the distribution of metformin pre-surgically in a cohort of patients diagnosed with breast cancer. In continuation of surgery, cancer tissue and healthy breast tissue will be collected from the patients and analyzed for the expression of organic cation transporters that are essential for metformin uptake.
Metformin has been on the market since the 50ies and is a well investigated, well tolerated and cheap drug. Positive effects of the metformin on breast cancer can save lives and prevent suffering for a large group of patients both In Denmark and Internationally. This study will bring new and important aspects on metformin pharmacokinetics, which are a prerequisite for implementation of metformin in the treatment of breast cancer.