The study, published in the journal Diabetes Care, adds to evidence that metformin, a generically available drug commonly used for type 2 diabetes, may have anti-cancer effects.
A number of epidemiological studies have found that among people with type 2 diabetes, metformin users may have lower risks of certain cancers. And a recent study in mice found that adding metformin to a chemotherapy drug called doxorubicin was more effective than the cancer drug alone in treating breast tumors.
Researchers at Harvard University are currently developing a large clinical trial to test whether using metformin after standard treatment for early breast cancer helps prevent cancer recurrence.
In the current study, researchers found that among more than 1,400 UK women using medication for type 2 diabetes, those who had been taking metformin for more than five years were 56 percent less likely to have breast cancer than women with no history of metformin use.
The association remained when the researchers accounted for factors such as the duration of a woman’s diabetes, use of additional diabetes medication or insulin, body weight and smoking habits.
Other oral diabetes drugs, as well as insulin, showed no clear relationship with breast cancer risk.
The possible beneficial effect of metformin was, however, based on a small number of women. Only 17 women had used metformin for more than five years and had a diagnosis of breast cancer.
Moreover, the design of the study precludes any conclusions about cause-and-effect, note the researchers, led by Dr. Christoph R. Meier of the University Hospital Basel in Switzerland.
The findings are based on the medical records of UK women between the ages of 30 and 79 who were being treated for type 2 diabetes. The researchers identified 305 women who had been diagnosed with breast cancer, and matched each with three or four cancer-free women the same age. They then looked at the women’s diabetes medication history to look for links to breast cancer risk.
Such studies can point to an association between two factors — in this case, metformin use and breast cancer risk — but cannot prove cause-and-effect.
Still, Meier’s team writes, the findings are in line with past research on the diabetes drug and breast cancer risk.
Type 2 diabetes arises when the body can no longer properly use insulin, a hormone that regulates blood glucose (sugar); this results in both high blood sugar and blood insulin levels. Insulin also promotes cell growth, and studies have linked elevated insulin levels to an increased risk of certain cancers, including breast, prostate and colon cancers.
Metformin helps lower insulin levels by inhibiting the liver’s production of glucose and boosting the body’s glucose absorption from the blood. This insulin reduction may help explain the drug’s link to a lower breast cancer risk, Meier’s team notes.
But research also suggests that metformin may more directly inhibit tumor growth, through its actions on an enzyme called AMPK.
The current findings, Meier and his colleagues write, add to the “increasing body of evidence” that metformin may have anti-cancer effects, and lend support to clinical trials testing the drug in women with both breast cancer and high insulin levels.
The study was funded by Merck Serono, maker of the metformin brand Glucophage.
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Diabetes Care, online March 18, 2010.