Population and laboratory studies have demonstrated that the anti-diabetic drug metformin has anti-breast cancer effects. Metformin has been shown to reduce risk of breast cancer and increase the efficacy of certain breast cancer treatments. This has led some observers to call for studying metformin as a treatment in non-diabetic patients. However, metformin has complex interactions with breast cancer and a new study has suggested that it might be unhelpful in women without insulin resistance.

Metformin prevents breasts cancer and improves survival in women with diabetes

Metformin treats type 2 diabetes by decreasing the production of glucose in the liver, enhancing the uptake of glucose in muscles, and reducing the level of blood glucose. Metformin also acts by increasing insulin sensitivity and reducing excess circulating insulin caused by insulin resistance. High circulating insulin has been shown to be associated with increased risk of breast cancer. Diabetic women taking metformin have a lower rate of breast cancer than those not treated with metformin.

Extensive studies have reported anticancer effects of metformin in all breast cancer subtypes in the laboratory, including in chemotherapy-resistant cells. Metformin has been shown to improve survival of diabetic women with HER2/neu overexpressing (HER2+) breast cancer and suppress metastasis of triple negative breast cancer cells.

Latest research finds metformin influences proliferation

The study referenced at the beginning of this news article was designed to investigate the effect of metformin on proliferation in breast cancer patients without diabetes. The change in proliferation (as measured by Ki-67) before and after breast cancer treatment has prognostic value and might predict antitumor activity. The change in proliferation can be determined by measuring Ki-67 in both the initial biopsy and post-treatment surgical specimens from the same woman.

The study included 200 non-diabetic women with operable breast cancer who were divided into two equal groups. One group received 850 mg of metformin twice per day whereas the other group received a placebo. The primary outcome was the difference in change in Ki-67 after four weeks between the two groups.

Metformin appeared to have no effect on the change in Ki-67 when the two groups of women were compared overall. On the other hand, metformin was found to decrease proliferation in women with insulin resistance and increase it in women without insulin resistance. The implication is that metformin might actually be harmful in breast cancer patients without insulin resistance. However, these differences reached statistical significance only in luminal B tumors (estrogen or progesterone receptor positive, often with low tumor grade, but with higher proliferation than other estrogen receptor positive tumors).

Insulin resistance also influenced the effect of metformin according to body mass index (BMI), waist/hip girth-ratio, moderate alcohol consumption, and C-reactive protein (a measure of inflammation). The authors conclude that metformin before surgery did not significantly affect proliferation overall, but had different effects according to insulin resistance, particularly in luminal B tumors. The findings warrant further studies of metformin's effects in breast cancer, according to the authors, with careful consideration of the metabolic characteristics of the study participants.

Please see our article on breast cancer and type 2 diabetes for more information.