Resveratrol, a phytochemical produced by a restricted number of plant species in response to stress, has exerted compelling breast cancer preventive activities in preclinical studies. Resveratrol not only acted as an estrogen receptor agonist/antagonist and inhibited aromatase but also affected multiple carcinogenesis pathways and multiple targets within a pathway. Resveratrol also demonstrated beneficial effects on metabolic disturbances in rodent models for obesity. We conducted an open label, single arm pilot study of resveratrol in postmenopausal women with high body mass index (BMI ≥ 25 kg/m2), a risk factor for breast cancer. The primary objective was to determine the effect of resveratrol on serum estradiol levels with secondary endpoints being measurement of modulation of multiple systemic markers associated with breast cancer risk. Forty eligible subjects were recruited to initiate the resveratrol intervention (1 gm resveratrol daily for 12 weeks) with six withdrawn early due to adverse events. Thirty-four subjects completed 12 weeks of resveratrol intervention. We found that resveratrol intervention did not result in significant changes in serum concentrations of estradiol, estrone, and testosterone in the study cohort but significantly increased serum levels of sex steroid hormone binding globulin (10% increase from baseline, p < 0.01). Resveratrol intervention resulted in a significant increase in urinary 2-hydroxyestrone (2-OHE1) levels (73% increase from baseline, p < 0.01) leading to a favorable change in urinary 2-OHE1/16α-OHE1 ratio (85% increase from baseline, p < 0.01). Serum leptin levels were suppressed significantly (10% decrease from baseline, p < 0.01) following resveratrol intervention whereas serum adiponectin levels were not changed. The most common possibly or probably related adverse events were diarrhea, constipation, and abdominal discomfort. One participant had a possibly related serious grade 4 elevation in hepatic ALT and AST enzymes at the post-intervention visit which resolved after less than 3 months of follow-up. Aside from this event, resveratrol intervention did not result in clinically significant changes in hematology and blood chemistry. We conclude that daily 1 gm dose of resveratrol did not affect the levels of circulating sex steroid hormones in postmenopausal women with high BMI but resulted in favorable changes in serum sex steroid binding globulin and leptin levels and urinary 2-OHE1/16α-OHE1 ratio that may be associated with reduced breast cancer risk. However, the observed adverse effects advocate for the consideration of lower doses for further clinical development of resveratrol for cancer prevention. (supported by a contract, N01-CN-35158, from the National Cancer Institute, Division of Cancer Prevention)

Citation Format: H-H. Sherry Chow, Linda L. Garland, Brandy M. Heckman-Stoddard, Chiu-Hsieh Hsu, Valerie D. Butler, Catherine A. Cordova, Wade M. Chew, Terri L. Cornelison. Modulating effects of resveratrol on systemic markers associated with breast cancer risk: a pilot clinical study in postmenopausal women with high adiposity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 159. doi:10.1158/1538-7445.AM2013-159