Background: In postmenopausal women, use of hormone therapy is associated with a lower incidence of diabetes (DM). The association of adjuvant endocrine therapy (AET) with DM has not been well studied among women treated for early stage breast cancer. The objective of this study was to examine the association of AET with risk of developing DM among postmenopausal women who developed breast cancer. Methods: 5,013 postmenopausal women from the Women’s Health Initiative diagnosed with non-metastatic breast cancer who were diabetes-free at cancer diagnosis and who had information on use of AET were included. AET use was gathered using 2 methods: 1) review of medication inventories for use of tamoxifen or aromatase inhibitors (AI) and 2) review of the Life and Longevity after Cancer (LILAC), a supplemental questionnaire used from 2009-2010 to gather treatment information from women who developed cancer. Results from these 2 collection methods were analyzed separately due to the timing of the surveys as well as data granularity (i.e. LILAC queried use of AET, not type). The primary outcome of interest for this study was diabetes-free survival, which was calculated from the date of breast cancer diagnosis to first diagnosis of DM. Participants who did not develop DM after breast cancer were censored at their last follow-up visit or date of death. Cox proportional hazards models were used to compute hazard ratios (HR) and 95% confidence intervals (CI). Results: After 10.4 median year’s follow-up post breast cancer diagnosis, 13% (632/5,013) of participants developed DM. Of the 2,646 who had medication inventory data, 1,352 (51%) reported AI use and 1,449 (55%) reported tamoxifen use. Participants who reported use of AIs were 13% more likely to develop DM than participants who did not use AIs (HR=1.13, CI=0.91-1.39). Participants who reported use of tamoxifen were 11% less likely to develop DM than those who did not use tamoxifen (HR=0.89, CI=0.72-1.11). Of the 3,769 participants with LILAC data from the supplemental questionnaire, 2,543 (67%) reported use of AET; these participants were 25% more likely to develop DM than those who did not use AET (HR=1.25, CI=1.02-1.53). When plotted over time, the risk of diabetes in AET users versus non-users was identical at 5 years (5% v 5%, respectively), was 35% higher at 10 years (12% v 9%, respectively), and 30% higher at 15 years (18% v 14%, respectively) (log-rank p=0.029). Conclusion: DM has not been reported as an adverse event in women on AET. Our data suggest an association of AET with DM among postmenopausal women with early stage breast cancer. When looking at specific types of AETs, the risk was marginally increased for AIs but marginally decreased for tamoxifen, with risk more apparent in subsequent years. These data have significance for survivorship care.

Citation Format: Joanne E Mortimer, Rebecca A Nelson, Laura Kruper, Kathy Pan, Christina M Dieli Conwright, Aladdin H Shadyab, Lewis Kuller, Barbara Howard, Rowan T Chlebowski. Association of adjuvant endocrine therapy with diabetes among women with postmenopausal breast cancer in the Women’s Health Initiative (WHI) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-12-04.