A new study has reported that women with type 2 diabetes and human epidermal growth factor receptor overexpressing (HER2+) breast cancer who use metformin have a much better prognosis than similar women who do not use metformin. The study was designed to investigate the influence of metformin and thiazolidinediones (all of which are used to treat type 2 diabetes) on the prognosis of women with HER2+ breast cancer. Note that safety issues have been raised with respect to the thiazolidinediones (Avandia, Actos, Rezulin) and they have either been withdrawn from the U.S. market or are not used for most patients.
Insulin and insulin-like growth factor I (IGF-I) signaling is thought to be one mechanism by which type 2 diabetes promotes cancer. Human epidermal growth factor receptors, insulin receptors, and IGF-I receptors are all involved with the same PI3K/AKT/mTOR signaling pathway. Various antidiabetic drugs may affect this signaling pathway differently, with varying influences on the prognosis of HER2+ patients.
To conduct the study, the authors reviewed the records of 1,983 consecutive patients with HER2+ breast cancer diagnosed between January 1, 1998 and September 30, 2010. Data was collected and analyzed with respect to age, body mass index (BMI), race, menopausal status, nuclear grade, tumor stage, estrogen (ER) and progesterone receptor (PR) status, as well as overall survival, breast cancer-specific survival, and types of antidiabetic drugs used.
Type 2 diabetes was found to be associated with poor survival of women with stage 2 or higher HER2+ breast cancer. The use of metformin and the use of thiazolidinediones were both associated with lengthened survival. When the analysis was restricted to those with diabetes, metformin was found to be associated with approximately double the likelihood of survival compared to no metformin or thiazolidinedione use. Metformin use was also associated with a similar decrease in risk of breast cancer-specific death. The authors conclude that thiazolidinediones and metformin users have better clinical outcomes than nonusers in diabetics with stage 2 or higher HER2+ breast cancer. The choice of antidiabetic medications may influence the prognosis of this group.
Comments regarding the study
This is the first study that has reported a survival benefit for diabetic HER2+ breast cancer patients who are taking metformin. Previous studies have found that metformin inhibits proliferation of Herceptin-resistant breast cancer stem cells and extends the life span of HER-2/neu transgenic mice (which spontaneously develop HER2+ mammary tumors). Metformin is currently being investigated as a treatment for women with HER2+ breast cancer who do not have type 2 diabetes.