Abstract P3-08-03: Urinary levels of prostaglandin E2 metabolite and postmenopausal breast cancer

Abstract

Abstract Estrogens are considered a key player in the mammary carcinogenesis. In postmenopausal women, peripheral aromatization of androgens is the predominant source of estrogens. Given that prostaglandin E2 (PGE2) is a potent activator of aromatase expression, we hypothesized that endogenous level of PGE2 would influence estrogen bioavailability and subsequent breast cancer risk in postmenopausal women. In addition, because PGE2 synthesis is suppressed by treatment of non-steroidal anti-inflammatory drugs (NSAIDs) via inhibition of cyclooxygenase enzyme activity, we further hypothesized that regular use of NSAIDs may modify the association between PGE2 and postmenopausal breast cancer risk. We carried out a case-cohort analysis within the NIEHS Sister Study, a prospective cohort study of 50,884 women. Postmenopausal women who were aged 50 or older and did not report current use of hormones were eligible for the present analysis (N = 11,338). Urinary levels of a major PGE2 metabolite (PGE-M), which is generally accepted as the most accurate index of endogenous PGE2 formation, were quantified using liquid chromatography/tandem mass spectrometry in 302 incident breast cancer cases and 305 subcohort members who were randomly selected by frequency matching for age among cases. Hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated using Prentice's pseudo-likelihood approach with Barlow's weighting scheme. Several factors were associated with higher levels of urinary PGE-M in the multivariable analysis, including current smoking, obesity, high caloric intake from saturated fat and surgical menopause. No associations were observed for dietary intake of omega 3 fatty acids, use of vitamin supplements and physical activity. Overall, there was no association between urinary PGE-M and postmenopausal breast cancer risk. After including the interaction terms between NSAID use and urinary levels of PGE-M in the model, however, high levels of urinary PGE-M were associated with an increased risk of breast cancer in postmenopausal women who did not regularly use NSAIDs (likelihood ratio test p <0.01). Taking into account use of NSAIDs 1 day prior to urine collection did not change results. NSAID use may modify the conversion of androgens to estrogen and thereby lower breast cancer risk. Expected data on estrogen and estrogen metabolites will help us better understand these findings. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P3-08-03.