Plasma phytoestrogens and subsequent breast cancer risk

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Introduction: Phytoestrogens are plant compounds that are structurally and functionally similar to mammalian estrogens. By competing for estrogen receptors, phytoestrogens possibly inhibit binding of the more potent endogenous estrogens and decrease their potential carcinogenic effects. We investigated the association between plasma phytoestrogen levels and breast cancer risk in a prospective manner. Methods: We performed a nested case-control study within the Prospect-EPIC cohort, one of the two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition. At the time of recruitment into the cohort, participants filled out medical, dietary and lifestyle questionnaires and blood samples were collected. A total of 388 women who developed breast cancer were selected as cases. From the same cohort 388 controls were selected, matched to the cases for date of blood sampling. Plasma levels of isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin (O-DMA) and equol) and lignans (enterodiol and enterolactone) were measured. For all analyses the isotope dilution liquid chromatography/ tandem mass spectrometry method incorporating triply C-labeled standards was used. Breast cancer odds ratios (OR) were calculated for tertiles of phytoestrogen plasma levels using conditional logistic regression analysis. Results were adjusted for established breast cancer risk factors. Results: For genistein, the risk estimate for the highest versus the lowest tertile was 0.68 (95% confidence interval; 0.47 –0.98). Similar protective effects, although not statistically significant, were seen for the other isoflavones. Lignan levels did not appear to be related to breast cancer risk. Conclusion: High circulating levels of isoflavones, especially genistein, may prevent against breast cancer. Effects of lignans on breast cancer risk are unclear.