Serum enterolactone and postmenopausal breast cancer risk by estrogen, progesterone and herceptin 2 receptor status

Abstract

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 5 0.65; 95% confidence interval (CI) 0.52-0.83, p trend 5 <0.0001]. A significant inverse association for ER1/PR1 as well as ER2/PR2 tumors was observed, with a significantly stronger association for ER2/PR2 tumors (p heterogeneity 5 0.03). The association for ER2/PR2 tumors did not differ by expression of HER2 (p heterogeneity 5 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 ER2PR2 than for ER1PR1 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.Phytoestrogens are a group of biologically active compounds that have been shown to protect against hormone-dependent cancers, in particular, breast cancer. 1-4 Their protective inverse association with breast cancer may be due to either estrogenic or antiestrogenic properties. [5][6][7][8] Because of their chemical structure, phytoestrogens can compete with endogenous estrogen for binding to the estrogen receptor (ER) of the tumor, thereby plausibly reducing the hormonal effect of the endogenous estrogens. 9 In addition to this, phytoestrogens also have antioxidative and antiproliferative properties and thereby may also reduce cancer risk. 10 The two main groups of phytoestrogens are the isoflavones and the lignans. Isoflavones, in particular, genistein, are mostly found in soy products. Only a few nonsoy plants contain isoflavones (e.g., legumes, grapefruit and raisins); but, at lower concentration, isoflavones do not importantly contribute to phytoestrogen intake in Western diets. 11,12 Plant lignans are widely present in whole grain, berries, vegetables, fruits, flaxseeds and other types of seeds and are the main source of phytoestrogens in Western populations....

Plasma enterolactone and breast cancer risk in the Nurses’ Health Study II

“…The median enterolactone level measured in our study is in accordance with the range of previously published circulating enterolactone concentrations in the US and Europe [49,29,50,36,37,30,51,52,28,53,54,33,55], but lower than that in Asia [56]. We did not observe an association between plasma enterolactone, a biomarker of lignan intake, and breast cancer risk either overall or by hormone receptor status.…”

“…Inconsistent results regarding the enterolactone-breast cancer association have been observed between retrospective studies and prospective studies, with case-control studies generally observing inverse association [26–28,31–34,41,35–38,29,30,39,40]. It is possible that breast cancer or its treatment could result in altered circulating enterolactone levels (e.g.…”

“…Retrospective studies have reported a decreased breast cancer risk with higher circulating enterolactone concentrations [26–30], but results from prospective studies have been conflicting [31–41]. However, previous studies suggested an inverse association between high enterolactone levels and postmenopausal breast cancer risk [29,37,38]. Thus, we prospectively examined the association of plasma enterolactone concentrations and breast cancer risk in a large study (802 cases and 802 matched controls) of predominantly premenopausal women nested within the Nurses’ Health Study II (NHSII) cohort for whom we have detailed information on case characteristics (e.g., estrogen and progesterone receptor (ER/PR) status) as well as dietary intake and circulating estradiol concentrations in the follicular and luteal phases.…”

Plant and mammalian lignans: A review of source, intake, metabolism, intestinal bacteria and health

“…Epidemiological and pharmacological studies reveal that END and its oxidation product ENL, in particular, afford protection against osteoporosis, cardiovascular diseases, hyperlipidemia, breast cancer, colon cancer, prostate cancer and menopausal syndrome (Adlercreutz, 2007;Feng, Shi, & Ye, 2008;Adolphe, Whiting, Juurlink, Thorpe & Alcom, 2010;Ayella et al, 2010;Zaineddin et al (2011).…”

Measuring exposure to the polyphenol metabolome in observational epidemiologic studies: current tools and applications and their limits

“…Similarly, lignan exposure has been inconsistently associated with postmenopausal breast cancer risk, both in studies based on lignan intake assessment (125, 132) and in studies based on lignan biomarkers (125, 137). The limited knowledge of the dietary precursors of mammalian lignans (114) makes the comparison between both types of studies difficult and suggests that current food-composition tables for the few lignans often present in trace amounts in foods are insufficient to assess exposure to mammalian lignans.…”