Enterolactone Is Differently Associated with Estrogen Receptor B–Negative and –Positive Breast Cancer in a Swedish Nested Case-Control Study

Background: Differences in the estrogen receptor (ER) status of tumors may explain ambiguities in epidemiologic studies between the blood concentrations of enterolactone and breast cancer. To our knowledge, the association between enterolactone and ERB-defined breast cancer has previously not been examined. Methods: A nested case-control study within the Malmö Diet and Cancer cohort used 366 cases and 733 matched controls to identify the major determinants of plasma enterolactone and to examine the association between enterolactone concentration and breast cancer risk and if this association differs depending on the ERA and ERB status of tumors. A modified diet history method assessed dietary habits. Time-resolved fluoroimmunoassay determined enterolactone concentrations and immunohistochemistry using tissue microarray determined ER status. Results: Dietary fiber, as well as fruits and berries, and high-fiber bread showed statistically significant correlations with enterolactone (r , 0.13-0.22). Smoking and obesity were associated with lower enterolactone concentrations. Enterolactone concentrations above the median (16 nmol/L) were associated with reduced breast cancer risk when compared with those below [odds ratio, 0.75; 95% confidence interval (95% CI), 0.58-0.98]. The reduced risk was only observed for ERA [positive (+); odds ratio, 0.73; 95% CI, 0.55-0.97] and ERB [negative ( )] tumors (odds ratio, 0.60; 95% CI, 0.42-0.84), with significantly different risks for ERB ( ) and ERB (+) tumors (P for heterogeneity = 0.04). Conclusions: This study supports the suggestion that enterolactone is a biomarker of a healthy lifestyle. The protective association between enterolactone and breast cancer was significantly different between ERB ( ) and ERB (+) tumors and most evident in tumors that express ERA but not ERB. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3241–51)