Abstract A12: Urinary levels of PGE-M and estrogens are independently associated with postmenopausal breast cancer risk

Prostaglandin E 2 (PGE 2 ) induces aromatase expression in adipose tissue leading to increased estrogen production that may promote the development and progression of breast cancer. However, few studies have simultaneously investigated systemic levels of PGE 2 and estrogen in relation to postmenopausal breast cancer risk. In a case-cohort study of postmenopausal women (295 cases and 294 subcohort) we previously reported that high levels of PGE-M, a major metabolite of PGE 2 , were associated with an increased risk of breast cancer among postmenopausal women who did not regularly use nonsteroidal anti-inflammatory drugs (NSAIDs). Here we determined urinary estrogen metabolites (EMs) using mass spectrometry in the same case-cohort set and using linear regression estimated the effect of PGE-M on EMs. Hazard ratios (HRs) for the risk of developing breast cancer in relation to PGE-M and EMs were evaluated in Cox regression models with and without mutual adjustment. PGE-M was a significant predictor of estrone (E1), but not estradiol (E2) levels in multivariable analysis. Elevated E2 levels were associated with an increased risk of developing breast cancer (HR Q5vs.Q1 =1.54, 95% CI: 1.01-2.35), and this association remained unchanged after adjustment for PGE-M (HR Q5vs.Q1 =1.52, 95% CI: 0.99-2.33). Similarly, elevated levels of PGE-M were associated with increased risk of developing breast cancer (HR Q4vs.Q1 =2.01, 95% CI: 1.01-4.29), and this association was only nominally changed after consideration of E1 or E2 levels. Urinary levels of PGE-M and parent estrogens were independently associated with future risk of developing breast cancer among these postmenopausal women. Increased breast cancer risk associated with PGE-M might be attributable both to PGE 2 -mediated increases in estrogens, and to additional effects related to inflammation. Note: This abstract was not presented at the conference. Citation Format: Sangmi Kim, Jeff Campbell, Wonsuk Yoo, Jack A. Taylor, Dale P. Sandler. Urinary levels of PGE-M and estrogens are independently associated with postmenopausal breast cancer risk. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr A12.