Gesundheitswesen 2017; 79(08/09): 656-804
DOI: 10.1055/s-0037-1605861
Vorträge
Georg Thieme Verlag KG Stuttgart · New York

Enterolactone levels and postmenopausal breast cancer survival: Assessment of mediation by inflammatory markers

S Jaskulski
1   German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg
,
AY Jung
1   German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg
,
T Johnson
1   German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg
,
K Thöne
2   University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Department of Cancer Epidemiology/Clinical Cancer Registry, Hamburg
,
D Sookthai
1   German Cancer Research Center (DKFZ), Division of Cancer Epidemiology, Heidelberg
,
J Chang-Claude
3   University Medical Center Hamburg-Eppendorf, University Cancer Center Hamburg, Genetic Tumour Epidemiology Group, Hamburg
› Author Affiliations
Further Information

Publication History

Publication Date:
01 September 2017 (online)

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Introduction:

In a meta-analysis we previously found evidence for protective effects of higher lignan exposure (dietary estimates or biomarkers) on both all-cause mortality (ACM) and breast cancer (BC)-specific mortality (BCSM) for postmenopausal BC patients. To identify hormone-independent mechanisms relating lignans to BC prognosis, we investigated for the first time whether and to what extent the association between enterolactone (ENL), the major lignan metabolite, and postmenopausal BC prognosis is mediated by inflammatory biomarkers.

Methods:

Data from a German patient cohort study of 2,115 BC patients (MARIE study) aged 50 – 74 years at diagnosis (2002 – 2005) and followed up until 2009 were used. Hazard ratios (HR) and 95%CIs were estimated using multivariable Cox regression. Examination of 18 measured inflammatory biomarkers yielded C-reactive protein (CRP) as the strongest hypothesized mediator. Mediation analysis was performed to estimate the percent of the association between ENL (log2) and both ACM and BCSM, which is mediated by CRP (log2), adjusting for age at diagnosis, prognostic factors and BMI.

Results:

Median serum/plasma ENL and CRP levels for all patients, including 221 deceased patients, were 22.2 and 16.7 nmol/L, and 4.5 and 8.4 mg/l, respectively. ENL levels were significantly inversely associated with both ACM and BCSM (per doubling of ENL levels: HR 0.93 (95%CI 0.88 – 0.99), p = 0.03 and HR 0.93 (0.86 – 1.00), p = 0.04, respectively). Including CRP into the models attenuated the associations for ACM (HR 0.94 (0.88 – 1.00), p = 0.05), and BCSM (HR 0.93 (0.86 – 1.00), p = 0.07). Preliminary analyses show that about 52.9%, and 52.1% of the effects of ENL on ACM and BCSM, respectively, were mediated through CRP.

Conclusions:

First findings indicate an intermediate effect of CRP on the association of ENL on postmenopausal BC survival. Further analyses will include evaluation of possible interactions between ENL and mediators, as well as sensitivity analyses.