Friday, September 7, 2012

Diabetes, metformin, and breast cancer

A number of interesting connections between obesity, diabetes,  the diabetes drug metformin, and breast cancer have been discovered in recent years. It has been known for some time that obesity is an adverse prognostic factor for breast cancer. For example, obese women have a higher risk of developing breast cancer compared to normal-weight woman, and women who have been treated for breast cancer who gain a lot of weight after treatment have a higher risk of recurrence than those that do not. The exact mechanism is not known, but it is thought that naturally-occurring insulin may play a role, since obese women tend to have higher levels of insulin and have relative insulin resistance. Additionally, women with diabetes who take metformin, a widely used agent to control blood sugar, may have a lower risk of cancer. This was shown in a recently published study in the Journal of Clinical Oncology. A large population-based clinical study called the Women's Health Initiative (WHI) looked at 68,019 women between 50-79 who did not have breast cancer at baseline. Of these 3,401 had diabetes at study entry. Women with diabetes treated with medications other than metformin had a slightly higher chance of developing breast cancer. By contrast women with diabetes treated with metformin had about a 25% lower breast cancer incidence. It is possible that metformin produced this finding by diminishing some of the effects that insulin-related cellular pathways had on cancer cells.

So does this mean that we are ready to prescribe metformin in women without diabetes as a treatment to lower the risk of breast cancer? No. However, this question is being studied in a large international clinical trial called MA.32 in which women without diabetes who have been curatively treated for breast cancer with surgery, with or without radiation, chemo, or hormonal therapy, are randomly assigned either to the drug metformin orally twice a day for 5 years or a placebo for 5 years. Interestingly, in non-diabetic women, metformin does not seem to cause much hypoglycemia (low blood sugar) as you might expect, and thankfully there are not a lot of other side effects. We won't know the results of this important study for a number of years, but if it does show a benefit to metformin in reducing breast cancer recurrence risk further, this old, widely-used, and inexpensive medication may be added to standard cancer therapies. This trial is available at Johns Hopkins for eligible patients.

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