Abstract 115: Enterolactone levels and prognosis after invasive postmenopausal breast cancer: Potential effect modifiers.
Authors: Seibold Petra , Buck Katharina , Vrieling Alina , Johnson Theron , Kaaks Rudolf , Linseisen Jakob , Heinz Judith , Obi Nadia , Flesch-Janys Dieter , Chang-Claude Jenny 
Published: August 2014

Abstract
Background: We previously reported that high levels of serum enterolactone, a metabolite of the phytoestrogen group of lignans, are associated with lower mortality in postmenopausal breast cancer patients (Buck et al. JCO 2011). Two subsequent studies confirmed this finding. In order to provide more insight into this association, we investigated whether enterolactone concentrations are affected by other lifestyle factors and tumor characteristics and whether the association might be restricted to subgroups defined by these factors.
Methods: To increase study power, we additionally measured enterolactone concentration in patients of the second study center of the two-center MARIEplus study. The 1,990 postmenopausal breast cancer patients, aged 50-74 years and diagnosed between 2001 and 2005 in Germany, were prospectively followed up until end of 2009. Vital status was assessed via local population registries, deaths were verified by death certificates. Information on the clinical course and treatment was collected and verified by clinical records. Hazard ratios (HR) and 95% confidence intervals (CI) for post-diagnostic enterolactone levels in relation to overall survival (OS) were estimated using delayed entry Cox proportional hazards models stratified by age at diagnosis and study center and adjusted for prognostic factors. Potential differential effects by hormone receptor status, HER2 status, tumor characteristics, and lifestyle factors such as BMI, physical activity and smoking, were assessed.
Results: Overall 257 patients had died. Median follow-up time from recruitment to death or censoring was 5.4 years. Median enterolactone levels for deceased and non-deceased patients were 17.3 and 20.8 nmol/L, respectively. Patients with high enterolactone levels were more likely to have tumors of smaller size, lower grade, hormone receptor expression positive and screen-detected, and to be HRT users, of normal weight and non-/former smokers and had not received chemotherapy. High enterolactone levels were associated with better OS (highest, Q4, vs. lowest quartile, Q1, HR 0.60, 95% CI 0.41-0.90). Per 10 nmol/L increment, HR was 0.94 (95% CI 0.90-0.98).
In subgroup analysis, we found a stronger inverse association with estrogen receptor (ER) negative tumors (Q4 vs. Q1, HR 0.39, 95% CI 0.16-0.93) than with ER positive tumors (HR 0.76, 0.46-1.25). Stronger associations were also observed in normal weight women (Q4 vs. Q1: HR 0.56, 0.35-0.90) than overweight women (HR 0.80, 0.36-1.75), in more active (HR 0.54, 0.33-0.90) than less active women (HR 0.78, 0.39-1.58) and in current smokers (HR 0.35, 0.14-0.89) than non-smokers/former smokers (HR 0.72, 0.46-1.13). However, subgroup differences were not statistically significant.
Conclusions: The inverse association of high enterolactone levels with overall mortality may be modified by hormone receptor status and lifestyle factors.
Citation Format: Petra Seibold, Katharina Buck, Alina Vrieling, Theron Johnson, Rudolf Kaaks, Jakob Linseisen, Judith Heinz, Nadia Obi, Dieter Flesch-Janys, Jenny Chang-Claude. Enterolactone levels and prognosis after invasive postmenopausal breast cancer: Potential effect modifiers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 115. doi:10.1158/1538-7445.AM2013-115