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Seibold, P.* ; Vrieling, A.* ; Johnson, T.S.* ; Buck, K.* ; Behrens, S.* ; Kaaks, R.* ; Linseisen, J. ; Obi, N.* ; Heinz, J.* ; Flesch-Janys, D.* ; Chang-Claude, J.*

Enterolactone concentrations and prognosis after postmenopausal breast cancer: Assessment of effect modification and meta-analysis.

Int. J. Cancer 135, 923-933 (2014)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
We previously reported that high concentrations of enterolactone, a lignan metabolite, are associated with lower mortality in 1,140 breast cancer patients from Germany. Using an extended set of 2,182 patients aged 50-74 years at diagnosis (2001-2005) and prospectively followed up until 2009, we investigated whether the association with mortality differs by lifestyle factors and tumor characteristics. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using multivariable Cox regression. Potential differential effects by tumor characteristics and lifestyle factors were assessed and a meta-analysis of five studies addressing lignan exposure and breast cancer prognosis was performed to summarize evidence. Median enterolactone concentrations were 17.4 (± 30.5 standard deviation) and 22.9 nmol/L (± 44.8), respectively, for 269 deceased and 1,913 patients still alive. High enterolactone concentrations were significantly associated with lower all-cause mortality (per 10 nmol/L: HR 0.94, 95% CI 0.90-0.98), breast cancer-specific mortality (HR 0.94, 0.89-0.99), and distant disease-free survival (HR 0.94, 0.90-0.98). Associations were found for stage I-IIIA but not for stage IIIB-IV disease (phet =0.01) and were stronger in patients with BMI<25 kg/m² than those with BMI≥25 (phet =0.04). In patients with healthy lifestyle (BMI<25, non-smoker, physically active), the inverse association with all-cause mortality was still apparent (HR 0.92, 0.85-0.99). The meta-analysis yielded significant associations both for all-cause (HR 0.57, 0.42-0.78) and breast cancer-specific mortality (HR 0.54, 0.39-0.75). Our findings show that high lignan exposure is associated with reduced mortality in breast cancer patients. The inverse association observed in this study cannot be entirely explained by a healthy lifestyle.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords breast cancer mortality; enterolactone; lignans; phytoestrogens; Serum Enterolactone; Food Sources; Phytoestrogens; Survival; Lignan; Flaxseed; Cohort; Enterolignans; Consumption; Women
ISSN (print) / ISBN 0020-7136
e-ISSN 1097-0215
Quellenangaben Volume: 135, Issue: 4, Pages: 923-933 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)