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

TY - JOUR

T1 - Enterolactone concentrations and prognosis after postmenopausal breast cancer: assessment of effect modification and meta-analysis

AU - Seibold, Petra

AU - Vrieling, Alina

AU - Johnson, Theron S

AU - Buck, Katharina

AU - Behrens, Sabine

AU - Kaaks, Rudolf

AU - Linseisen, Jakob

AU - Obi-Osius, Nadia

AU - Heinz, Judith

AU - Flesch-Janys, Dieter

AU - Chang-Claude, Jenny

N1 - © 2014 UICC.

PY - 2014/8/15

Y1 - 2014/8/15

N2 - 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.

AB - 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.

KW - 4-Butyrolactone

KW - Aged

KW - Body Mass Index

KW - Breast Neoplasms

KW - Diet

KW - Disease Progression

KW - Disease-Free Survival

KW - Female

KW - Germany

KW - Humans

KW - Life Style

KW - Lignans

KW - Middle Aged

KW - Postmenopause

KW - Prognosis

KW - Proportional Hazards Models

KW - Prospective Studies

KW - Risk Factors

KW - Tumor Markers, Biological

U2 - 10.1002/ijc.28729

DO - 10.1002/ijc.28729

M3 - SCORING: Journal article

C2 - 24436155

VL - 135

SP - 923

EP - 933

JO - INT J CANCER

JF - INT J CANCER

SN - 0020-7136

IS - 4

ER -