Plasma Phytoestrogens and Subsequent Breast Cancer Risk

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

doi:10.1200/jco.2006.06.0244

Cited by 146 publications

(104 citation statements)

References 35 publications

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“…The combined OR (summary OR ¼ 1.02, 95% CI ¼ 0.84 -1.23) from these three nested case -control studies is consistent with the finding of no association based on dietary soy isoflavones and breast cancer risk in Western populations. There were no differences in results by menopausal status (Horn-Ross et al, 2001;dos Santos Silva et al, 2004;Keinan-Boker et al, 2004;Bosetti et al, 2005;Fink et al, 2007;Verheus et al, 2007). One study examined the soy -breast cancer association by body size and reported no differences in results (Bosetti et al, 2005).…”

Section: Risk Association Studies In Low-soy-consuming Western Populamentioning

confidence: 97%

“…To overcome the difficulties and imprecision associated with estimating low dietary soy intake from questionnaires, baseline, prediagnostic blood/urine isoflavone levels collected from participants of three cohorts were examined in relation to breast cancer risk (den Tonkelaar et al, 2001;Grace et al, 2004;Verheus et al, 2007); two of these studies also had information on dietary soy isoflavone intake (Grace et al, 2004;Keinan-Boker et al, 2004). The combined OR (summary OR ¼ 1.02, 95% CI ¼ 0.84 -1.23) from these three nested case -control studies is consistent with the finding of no association based on dietary soy isoflavones and breast cancer risk in Western populations.…”

Section: Risk Association Studies In Low-soy-consuming Western Populamentioning

confidence: 99%

“…Fourteen studies were included in the meta-analysis by Trock et al (2006). Of the remaining 14 studies, 6 were conducted in Asia (Hirose et al, 2005;Lee et al, 2005;Shannon et al, 2005;Ho et al, 2006;Do et al, 2007;Nishio et al, 2007) while the rest were conducted in various Western populations (Peterson et al, 2003;dos Santos Silva et al, 2004;Keinan-Boker et al, 2004;Bosetti et al, 2005;Thanos et al, 2006;Touillaud et al, 2006;Fink et al, 2007;Verheus et al, 2007). Given that Asians differ from Western populations in terms of types and amounts of soy consumed, and possess distinct characteristics linked to breast cancer risk, we conducted separate meta-analysis on epidemiologic data derived from Asians and Western populations, respectively.…”

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Epidemiology of soy exposures and breast cancer risk

et al. 2008

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Most of the early studies published on soy and breast cancer were not designed to test the effect of soy; the assessment of soy intake was usually crude and few potential confounders were considered in the analysis. In this review, we focused on studies with relatively complete assessment of dietary soy exposure in the targeted populations and appropriate consideration for potential confounders in the statistical analysis of study data. Meta-analysis of the 8 (1 cohort, 7 case -control) studies conducted in high-soy-consuming Asians show a significant trend of decreasing risk with increasing soy food intake. Compared to the lowest level of soy food intake (p5 mg isoflavones per day), risk was intermediate (OR ¼ 0.88, 95% confidence interval (CI) ¼ 0.78 -0.98) among those with modest (B10 mg isoflavones per day) intake and lowest (OR ¼ 0.71, 95% CI ¼ 0.60 -0.85) among those with high intake (X20 mg isoflavones per day). In contrast, soy intake was unrelated to breast cancer risk in studies conducted in the 11 low-soy-consuming Western populations whose average highest and lowest soy isoflavone intake levels were around 0.8 and 0.15 mg per day, respectively. Thus, the evidence to date, based largely on case -control studies, suggest that soy food intake in the amount consumed in Asian populations may have protective effects against breast cancer.

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Section: Risk Association Studies In Low-soy-consuming Western Populamentioning

confidence: 97%

Section: Risk Association Studies In Low-soy-consuming Western Populamentioning

confidence: 99%

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confidence: 99%

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Epidemiology of soy exposures and breast cancer risk

et al. 2008

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“…[14][15][16][17][18][19][20][21] Two recently published metaanalyses (including our own) showed that high serum or urinary enterolactone levels were associated with a nonsignificant reduced postmenopausal breast cancer risk, whereas high consumption of dietary lignans was associated with a significant reduced postmenopausal breast cancer risk. 22,23 The objective of our study was to examine the association of the major serum enterolignan (enterolactone) with the risk of postmenopausal breast cancer in a large German study population with Western dietary habits.…”

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confidence: 99%

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

Zaineddin

Vrieling

Buck

et al. 2011

Intl Journal of Cancer

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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....

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“…Evidence that these compounds are biologically active even at low levels in humans comes from interactions between phytoestrogens and gene variants of the estrogen receptor (ESR1 and NR1I2) (11,12), sex-hormone binding globulin (SHBG) (13), and probably aromatase (CYP19) (14). Recent studies have shown either increased or decreased breast cancer risk associated with phytoestrogens at low levels (15)(16)(17). However, these compounds can act as either estrogens or anti-estrogens, leading to concerns surrounding the use of phytoestrogen supplements in breast cancer patients (18,19).…”

Section: Introductionmentioning

confidence: 99%

Phytoestrogen Content of Foods of Animal Origin: Dairy Products, Eggs, Meat, Fish, and Seafood

Kuhnle

Dell'Aquila

Aspinall

et al. 2008

J. Agric. Food Chem.

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126

101

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Dietary phytoestrogens may be involved in the occurrence of chronic diseases. Reliable information on the phytoestrogen content in foods is required to assess dietary exposure and disease risk in epidemiological studies. However, existing analyses have focused on only one class of these compounds in plant-based foods, and there is only little information on foods of animal origin, leading to an underestimation of intake. This is the first comprehensive study of phytoestrogen content in animal food. We have determined the phytoestrogen content (isoflavones: biochanin A, daidzein, formononetin, genistein, and glycitein; lignans: secoisolariciresinol and matairesinol; coumestrol; equol; enterolactone; and enterodiol) in 115 foods of animal origin (including milk and milk-products, eggs, meat, fish, and seafood) and vegetarian substitutes using liquid chromatography-mass spectrometry (LC-MS) with 13 C-labeled internal standards. Phytoestrogens were detected in all foods analyzed; the average content was 20 µg/100 g of wet weight (isoflavones, 6 µg/100 g; lignans, 6 µg/100 g; equol, 3 µg/100 g; and enterolignans, 6 µg/100 g). In infant soy formula, 19 221 µg/100 g phytoestrogens were detected (compared to 59 µg/100 g in non-soy formula). Our study shows that all foods analyzed contained phytoestrogens and most foods (except for fish, seafood, and butter) contained mammalian phytoestrogens (enterolignans and equol). This is the first comprehensive study of phytoestrogen content of foods of animal origin and will allow for a more accurate estimation of exposure to dietary phytoestrogens.

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Plasma Phytoestrogens and Subsequent Breast Cancer Risk

Abstract: 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.

Cited by 146 publications

References 35 publications

Epidemiology of soy exposures and breast cancer risk

Epidemiology of soy exposures and breast cancer risk

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

Phytoestrogen Content of Foods of Animal Origin: Dairy Products, Eggs, Meat, Fish, and Seafood

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