Lignans are a group of
estrogenic compounds present in plants. Several epidemiological studies proposed that
lignans may protect against
breast cancer by exerting anticarcinogenic activity. Levels of
enterolactone were determined in serum samples of 1,250 cases and 2,164 controls from a large population-based case-control study. We assessed the association between serum
enterolactone and postmenopausal
breast cancer risk using conditional logistic regression accounting for potential risk and confounding factors. Fractional polynomials were used to determine the function that best fitted the data. Moreover, we assessed heterogeneity by
estrogen/
progesterone/
herceptin (ER/PR/HER2) status of the
tumor. Additionally, a meta-analysis with seven further studies addressing
enterolactone concentrations and
breast cancer risk was performed. Postmenopausal
breast cancer risk decreased with increasing serum
enterolactone levels [highest compared to lowest quintile: [odds ratio = 0.65; 95% confidence interval (CI) 0.52-0.83, p(trend) = < 0.0001]. A significant inverse association for ER+/PR+ as well as ER-/PR-
tumors was observed, with a significantly stronger association for ER-/PR-
tumors (p(heterogeneity) = 0.03). The association for ER-/PR-
tumors did not differ by expression of HER2 (p(heterogeneity) = 0.3). The meta-analysis yielded a significant reduced pooled risk estimate of: 0.66; 95% CI: 0.55-0.77) comparing the highest to the lowest quantiles of
enterolactone levels. We found strong evidence for a significant inverse association between serum
enterolactone and postmenopausal
breast cancer risk, which was stronger for ER-PR- than for ER+PR+
tumors but not differential by further expression of HER2. The overall evidence together with other studies supports an inverse association between higher serum
enterolactone levels and postmenopausal
breast cancer risk.