Impact of Diabetes, Insulin, and Metformin Use on the Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Primary Breast Cancer: Analysis From the ALTTO Phase III Randomized Trial

Authors: Sonnenblick, A et. al.

Source: J Clin Oncol 35:1421-4129

ascopubs.org/doi/abs/10.1200/JCO.2016.69.7722

High levels of insulin, and insulin resistance, appear to play roles in the poorer prognosis of breast cancer among diabetic patients. Metformin, a drug used to treat many cases of diabetes, has anti-breast cancer effects. More information is needed to determine if metformin truly improves survival after breast cancer among diabetics.

The ALTTO Trial evaluated the effects of HER2-targeted therapies on outcomes of HER2-positive breast cancer. More than 8,000 women were included in the study, and over 400 of them had diabetes. The investigators looked more closely at this subgroup and evaluated their outcomes.

The women with diabetes were more likely to be older, postmenopausal, have higher body mass indices (BMI) and to have larger tumors. The diabetic women had overall worse outcomes compared to the women who did not have diabetes.

However, within the group of diabetic women, those who took metformin had significantly improved outcomes compared to those who did not. Metformin use was associated with improved disease-free, distant disease-free and overall survival. Of note, these differences applied only to hormone (estrogen and progesterone) receptor-positive breast cancer cases.

These promising results pave the way to consider prescribing metformin for some diabetic women with HER2-positive, hormone receptor-positive breast cancer. The observed improved outcomes should be evaluated on a larger scale.