Abstract 3030: Effect of 6 months of bazedoxifene and conjugated estrogen on measures of insulin resistance in postmenopausal women at increased risk for breast cancer
Authors: Fabian Carol J. , Giles Erin D. , Cook Katherine L. , Powers Kandy , Altman Christy , Kreutzjans Amy , Phillips Teresa , Zelenchuk Adrian , Pittman Krystal , Hursting Stephen D. , Kimler Bruce 
Published: April 2023

Abstract
Background: Bazedoxifene 20 mg (BZA) + Conjugated estrogen 0.45 mg (CE) as Duavee™ is FDA approved for treatment of hot-flashes and prevention of osteoporosis. We are investigating 6 months of BZA + CE vs wait list control in a multisite Phase IIB trial for primary prevention of breast cancer in high-risk peri-and postmenopausal women with vasomotor symptoms. Primary endpoints are change in mammographic fibroglandular volume and normal breast epithelial proliferation as assessed by Ki-67. Menopause transition is marked by an increase in insulin resistance and incidence of metabolic syndrome which in turn are implicated in the development of breast cancer. Tamoxifen can induce insulin resistance due to effects on small adipocytes, pancreatic beta cells, and hepatic lipid accumulation. In contrast, preclinical studies suggest that BZA + CE may have favorable effects on insulin resistance, particularly in obese animals. Consequently, we are exploring effects of BZA + CE on measures of insulin resistance in our clinical trial.
Methods: Fasting plasma was assessed for insulin and glucose in a CLIA laboratory the same day as drawn. HOMA-IR (insulin resistance) was computed as insulin (µU/ml) × glucose (mg/dl)]/405) and HOMA-%S (measure of insulin sensitivity) as 100/HOMA-IR. HOMA-IR ≥ 1.9 is considered an indication of early insulin resistance and HOMA-IR &gt;2.8 significant insulin resistance. HOMA-%S values of ≥100% are considered an indication of insulin sensitivity.
Results: 21 women have been randomized in the initial 10 months of accrual at the University of Kansas Cancer Center with 8 women completing the 6 -month randomized period to date. Median age was 53 (48-56), and median BMI was 25 kg/m2 (22-35 kg/m2). All women were normoglycemic. However, 2 women (1 each BZA + CE and wait list) had baseline evidence of insulin resistance by HOMA IR (≥1.9). In the woman randomized to BZA + CE, HOMA-IR improved from 2.29 at baseline to 1.0 at 6 months and HOMA-%S improved from 44 to 100%. There was little change in insulin resistance measures in the woman with baseline insulin resistance randomized to wait list. HOMA-IR was 2.83 at baseline and 2.76 at 6 months and HOMA-%S 35% at baseline and 36% at 6 months. Another waitlist participant with normal baseline HOMA-%S of 141% dropped to 71% at 6 months. Results will be available for 20 study participants at the meeting.
Summary: In our initial accrual group there is no indication that 6 months of BZA +CE is associated with development of insulin resistance. Funded in part by NIH grant CA249437 and Breast Cancer Research Foundation grants BCRF-21-049 and BCRF-22-049.
Citation Format: Carol J. Fabian, Erin D. Giles, Katherine L. Cook, Kandy Powers, Christy Altman, Amy Kreutzjans, Teresa Phillips, Adrian Zelenchuk, Krystal Pittman, Stephen D. Hursting, Bruce Kimler. Effect of 6 months of bazedoxifene and conjugated estrogen on measures of insulin resistance in postmenopausal women at increased risk for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3030.