title: Enterolactone concentrations and prognosis after postmenopausal breast cancer: assessment of effect modification and meta-analysis.
abstract: 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(-1) (± 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(-1) : 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 0-IIIA but not for stage IIIB-IV disease (p(het) = 0.01) and were stronger in patients with BMI <25 kg m(-2) than those with BMI ≥ 25 (p(het) = 0.04). In patients with healthy lifestyle (BMI <25, nonsmoker, 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.
authors.affiliation: Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Seibold
authors.forename: Alina
authors.initials: A
authors.lastname: Vrieling
authors.forename: Theron S
authors.initials: TS
authors.lastname: Johnson
authors.forename: Katharina
authors.initials: K
authors.lastname: Buck
authors.forename: Sabine
authors.initials: S
authors.lastname: Behrens
authors.forename: Rudolf
authors.initials: R
authors.lastname: Kaaks
authors.forename: Jakob
authors.initials: J
authors.lastname: Linseisen
authors.forename: Nadia
authors.initials: N
authors.lastname: Obi
authors.forename: Judith
authors.initials: J
authors.lastname: Heinz
authors.forename: Dieter
authors.initials: D
authors.lastname: Flesch-Janys
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000097:blood; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D015992:Body Mass Index; D001943:Breast Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D004032:Diet; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005858:Germany; D006801:Humans; D008019:Life Style; D017705:Lignans / Q000097:blood*; D008875:Middle Aged; D017698:Postmenopause; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors
chemical_list: D014408:Biomarkers, Tumor; D017705:Lignans; D015107:4-Butyrolactone; C029497:2,3-bis(3'-hydroxybenzyl)butyrolactone
keywords: breast cancer mortality; enterolactone; lignans; phytoestrogens