Metformin is a widely-used anti-diabetic drug taken by people with type 2 diabetes. Evidence is accumulating that it also prevents the growth of cancers. Obese and diabetic people with high levels of insulin are at greater risk than the general population for developing cancer and dying from it. However, diabetics taking metformin are less likely to develop cancer or die from it. Diabetic women with breast cancer, taking metformin, have a better treatment response than diabetic women not taking metformin. A recent study shows that metformin represses the self-renewal of breast cancer stem cells (Jung, J.-W. et al.).
Cancer cells need glucose and insulin
When you grow breast cancer cells in the laboratory, you need to add a lot of glucose, insulin and other growth factors to the cell media, otherwise the cells will die. Normal breast cells can grow without or with very little insulin and glucose. This finding may explain why obese women, who are insulin -resistant (having high blood levels of insulin, but are not diabetic) and type 2 diabetics are at higher risk of breast cancer and breast cancer progression.
How metformin works
Metformin works by reducing glucose production in the liver and by increasing the uptake of glucose by muscles. This lowers glucose levels and tells the pancreas not to secrete insulin, thereby lowering blood insulin levels. When metformin was added to breast cancer cells, which had been stimulated with estrogen or endocrine-disrupting chemicals, the growth of cancer cells that depend on estrogen was suppressed.
A recent study suggests that metformin may also reduce cancer risk by reducing reactive oxygen molecules that can damage DNA. Accumulated DNA damage causes mutations and mutations can cause cancer.
Metformin breast cancer trial
The National Cancer Institute is starting a clinical trial with metformin to treat early-stage breast cancer. The trial, called Phase III Trial of Metformin versus Placebo in Early Stage Breast Cancer (CAN-NCIC-MA32), was recruiting non-diabetic women or men under the age of 75, diagnosed with early stage breast cancer. Participants will be treated with metformin or a placebo after undergoing surgery, such as lumpectomy or mastectomy. All patients will receive standard follow-up treatment in conjunction with metformin. The trial will last five years. This trial should tell if metformin combats breast cancer even in non-diabetic patients.
Sources
Jung, J.-W. et al. Metformin Represses Self-Renewal of the Human Breast Carcinoma Stem Cells via Inhibition of Estrogen Receptor-Mediated OCT4 Expression. PLoS ONE (2011) 6,e28068, doi: 10.1371/journal.pone.0028068
Taubes, G. Unraveling the Obesity-Cancer Connection. Science (2012) 335, 28
http://www.sciencedaily.com/releases/2011/11/111123190358.htm
http://www.sciencedaily.com/releases/2012/01/120118132334.htm
http://www.cancer.gov/ncicancerbulletin/053111/page6