Levels of the cyclooxygenase 2 (COX2) enzyme are elevated in breast cancer tissue, and most COX2 effects are believed to be mediated through overproduction of prostaglandin E2 (PGE2). We evaluated associations between the primary urinary metabolite of PGE2 (PGE-M) and breast cancer risk. A nested case-control study of 504 cases and 1,082 controls was conducted using data from the Shanghai Women's Health Study, a large population-based prospective cohort study of 74,941 Chinese women. Urinary PGE-M was measured using a liquid chromatography/tandem mass spectrometric method. Logistic regression estimated odds ratios (OR) and 95% confidence intervals (95% CI) with adjustment for potential confounders. Overall, no association between urinary PGE-M and breast cancer was detected. However, a suggestive positive association was found among postmenopausal women. In particular, a clear dose-response relationship between urinary PGE-M and breast cancer was observed among postmenopausal women with a body mass index (BMI) < 25 kg/m(2) (Plinear trend = 0.005). Among these women, risk of breast cancer increased from 1.00 (reference) to 1.06 (95% CI, 0.56-1.99), 1.50 (95% CI, 0.79-2.83), and 2.32 (95% CI, 1.24-4.41) for the lowest to highest quartiles of PGE-M, and such associations were stronger among those who were diagnosed with cancer within the first four years of sample collection. No apparent association was observed among overweight postmenopausal women (BMI ≥ 25 kg/m(2)). High urinary PGE-M level was associated with elevated risk of breast cancer among normal weight, postmenopausal women. Urinary PGE-M level may be useful for breast cancer risk assessment among normal weight, postmenopausal women. Cancer Epidemiol Biomarkers Prev; 23(12); 2866-73. ©2014 AACR.