Originally published as JCO Early Release 10.1200/JCO.2006.06.0244 on January 2 2007

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Plasma Phytoestrogens and Subsequent Breast Cancer Risk

Martijn Verheus, Carla H. van Gils, Lital Keinan-Boker, Philip B. Grace, Sheila A. Bingham, Petra H.M. Peeters

From the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands; Israel Center for Disease Control, Ministry of Health, and School of Public Health, University of Haifa, Haifa, Israel; Horseracing Forensic Laboratory Ltd, Fordham; and the Medical Research Council Dunn Human Nutrition Unit, Cambridge, United Kingdom

Address reprint requests to Petra H.M. Peeters, MD, PhD, Julius Center for Health Sciences and Primary Care, Room Str 6.131, PO Box 85500, University Medical Center, Utrecht 3508 GA, Utrecht, the Netherlands; e-mail: P.H.M.Peeters{at}umcutrecht.nl

PURPOSE: 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 effects on breast cancer risk. We investigated the association between plasma phytoestrogen levels and breast cancer risk in a prospective manner.

PATIENTS AND METHODS: We performed a nested case-control study within the Prospect cohort, one of the two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition. A total of 383 women (87 pre- or perimenopausal women [mean age, 52 years] and 296 postmenopausal women [mean age, 59 years]) who developed breast cancer were selected as case subjects and were matched to 383 controls, on date of blood sampling. Plasma levels of isoflavones (daidzein, genistein, glycitein, O-desmethylangolensin, and equol) and lignans (enterodiol and enterolactone) were measured. The isotope dilution liquid chromatography/tandem mass-spectrometry method incorporating triply ¹³C-labeled standards was used for all analyses. Breast cancer odds ratios were calculated for tertiles of phytoestrogen plasma levels using conditional logistic regression analysis.

RESULTS: For genistein, the risk estimate for the highest versus the lowest tertile was 0.68 (95% CI, 0.47 to 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. Results were the same in pre- or perimenopausal women, and in postmenopausal women.

CONCLUSION: High genistein circulation levels are associated with reduced breast cancer risk in the Dutch population. No effects of lignans on breast cancer risk were observed.

published online ahead of print at www.jco.org on January 2, 2007.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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