170-OR: Tamoxifen Treatment Causes Insulin Resistance in Obese Mice

Breast cancer survivors treated with the selective estrogen receptor modulator tamoxifen have an elevated risk for developing type 2 diabetes (T2D) compared with cancer-free individuals, especially in the context of obesity. Half of T2D diagnoses in breast cancer survivors are attributable to the cancer therapy itself. The underlying mechanisms of tamoxifen-induced T2D are unknown. We hypothesized that the detrimental impact of tamoxifen on insulin sensitivity was mediated by changes in the liver and skeletal muscle, and was exacerbated by high fat diet (HFD). Ovariectomized female mice supplemented with estradiol were randomized to low fat diet (LFD), LFD + tamoxifen, HFD, or HFD + tamoxifen. In general, our preclinical model recapitulated the observations from epidemiological studies on breast cancer survivors. HFD + tamoxifen mice had greater body fat percentage and fasting glucose (P Disclosure R.L. Scalzo: None. S.E. Hull: None. J.E.B. Reusch: Board Member; Self; American Diabetes Association. Other Relationship; Self; Merck & Co., Inc. P. MacLean: Advisory Panel; Self; Habit LLC. E. Wellberg: None. Funding Susan G. Komen Foundation; National Institutes of Health