1: Biochem Soc Trans 2001 May;29(Pt 2):209-16
Do dietary phytoestrogens influence susceptibility to hormone-dependent cancer by disrupting the metabolism of endogenous oestrogens?
Kirk CJ, Harris RM, Wood DM, Waring RH, Hughes PJ.
Phytoestrogens are natural constituents of our diets that have been suggested to protect against hormone-dependent breast cancer. Some of the diverse effects of these compounds may be attributed to ligand-dependent differences in their interaction with oestrogen receptor sub-classes. However, phytoestrogens can also inhibit enzymes that are involved in the generation and removal of endogenous steroid hormones. Among the most potent effects of dietary phytoestrogens is their ability to inhibit the sulphotransferases that sulphate both oestrogenic steroids and a variety of environmental chemicals, including dietary pro-carcinogens. Circulating steroid sulphates are thought to be the major source of oestradiol in post-menopausal breast tumours and sulphation is a key step in the activation of some dietary pro-carcinogens. Hence the inhibition of sulphotransferases by dietary phytoestrogens may have complex effects upon human susceptibility to breast cancer.
PMID: 11356156 [PubMed - indexed for MEDLINE]
1: Endocr Relat Cancer 2001 Jun;8(2):129-34
Phytoestrogens after breast cancer.
This P, De La Rochefordiere A, Clough K, Fourquet A, Magdelenat H; The Breast Cancer Group of the Institut Curie.
The current extension of the indications for adjuvant chemotherapy, which predisposes to early menopause, and the media coverage of the benefits of hormone replacement therapy (HRT) have led patients with a history of breast cancer to seek treatments for estrogen deprivation. In breast cancer survivors, most physicians avoid HRT because of concern regarding the potential promotion of growth of occult malignant cells by estrogens, due to the estrogen dependence of breast cancer. Soy phytoestrogens are being promoted as the 'natural alternative' to HRT and have been available without restrictions for several years as nutritional supplements. In this paper, data on the complex mammary effects of phytoestrogens in epidemiological studies, in in vitro studies, as well as in in vivo studies on animal carcinogenesis are reviewed. The potential benefits and risks of phytoestrogens are analyzed, and the prescription of phytoestrogens to postmenopausal women after breast cancer and the coprescription with the anti-estrogen tamoxifen are discussed. The absence of controlled trials and technical checking of extraction and titration in these preparations on 'free sale' raise a new problem in terms of public health and justify close reasoning and a cautious attitude of physicians, as well as straight information given to women, especially after breast cancer.
Publication Types: Review Review, Tutorial
PMID: 11397668 [PubMed - indexed for MEDLINE]
1: Cancer Res 2001 Jul 1;61(13):5045-50
Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner.
Allred CD, Allred KF, Ju YH, Virant SM, Helferich WG.
Department of Food Science and Human Nutrition, University of Illinois, Urbana, Illinois 61801, USA.
We have demonstrated that the isoflavone, genistein, stimulates growth of estrogen-dependent human breast cancer (MCF-7) cells in vivo (C. Y. Hsieh et al., Cancer Res., 58: 3833-3838, 1998). The isoflavones are a group of phytoestrogens that are present in high concentrations in soy. Whether consumption of genistein from soy protein will have similar effects on estrogen-dependent tumor growth as pure genistein has not been investigated in the athymic mouse tumor implant model. Depending on processing, soy protein isolates vary widely in concentrations of genistein. We hypothesize that soy isolates containing different concentrations of genistein will stimulate the growth of estrogen-dependent cells in vivo in a dose-dependent manner. To test this hypothesis we conducted experiments in which these soy protein isolates were fed to athymic mice implanted s.c. with estrogen-dependent tumors. Genistein content (aglycone equivalent) of the soy isolate diets were 15, 150, or 300 ppm. Positive (with 17beta-estradiol pellet implant) and negative (no 17beta-estradiol) control groups received casein-based (isoflavone-free) diets. Tumor size was measured weekly. At completion of the study animals were killed and tumors collected for evaluation of cellular proliferation and estrogen-dependent gene expression. Incorporation of bromodeoxyuridine into cellular DNA was used as an indicator of cell proliferation, and pS2 mRNA was used as an estrogen-responsive gene. Soy protein diets containing varying amounts of genistein increased estrogen-dependent tumor growth in a dose-dependent manner. Cell proliferation was greatest in tumors of animals given estrogen or dietary genistein (150 and 300 ppm). Expression of pS2 was increased in tumors from animals consuming dietary genistein (150 and 300 ppm). Here we present new information that soy protein isolates containing increasing concentrations of genistein stimulate the growth of estrogen-dependent breast cancer cells in vivo in a dose-dependent manner.
PMID: 11431339 [PubMed - indexed for MEDLINE]
1: Drug Saf 2001;24(9):665-82
Risks and benefits of soy phytoestrogens in cardiovascular diseases, cancer, climacteric symptoms and osteoporosis.
Phytoestrogens, plant chemicals classified as isoflavones, coumestans and lignans, display estrogen-like activity because of their structural similarity to human estrogens and exhibit high affinity binding for the estrogen receptor beta. They are common components of food items such as grains, beans, fruits and nuts. Isoflavones are primarily found in soybeans and foods made from soy. In particular, significant therapeutic properties have been generally attributed to soy isoflavones, but most of the claims have been poorly, or not at all, confirmed by well designed clinical trials. Such is the case of the purported role of soy isoflavones in reducing plasma cholesterol levels. This link is now not supported by many authors or by appropriately designed clinical studies. The role of isoflavones in cancer prevention, particularly of tumours under endocrine control (breast, prostate and others) is again only supported by weak to nonexisting clinical evidence. A similarcase is that of the prevention/treatment of postmenopausal symptoms and osteoporosis. Disturbing data have been reported on potential negative effects of soy isoflavones on cognitive function in the aged, particularly relating to tofu intake. Recent studies have finally indicated a potential role for soy isoflavones in inducing chromosomal changes in cells exposed in vitro and potentiating chemical carcinogens. These findings may not, however, be extrapolated to clinical conditions. Available data do not appear to unequivocally support beneficial effects of soy isoflavones, and warn against their wide use, in the absence of satisfactory clinical findings.
Publication Types: Review Review, Tutorial
PMID: 11522120 [PubMed - indexed for MEDLINE]
1: Am J Epidemiol 2001 Sep 1;154(5):434-41
Phytoestrogen consumption and breast cancer risk in a multiethnic population: the Bay Area Breast Cancer Study.
Horn-Ross PL, John EM, Lee M, Stewart SL, Koo J, Sakoda LC, Shiau AC, Goldstein J, Davis P, Perez-Stable EJ.
Research on the relation between phytoestrogens and breast cancer risk has been limited in scope. Most epidemiologic studies have involved Asian women and have examined the effects of traditional soy foods (e.g., tofu), soy protein, or urinary excretion of phytoestrogens. The present study extends this research by examining the effects of a spectrum of phytoestrogenic compounds on breast cancer risk in non-Asian US women. African-American, Latina, and White women aged 35-79 years, who were diagnosed with breast cancer between 1995 and 1998, were compared with women selected from the general population via random digit dialing. Interviews were conducted with 1,326 cases and 1,657 controls. Usual intake of specific phytoestrogenic compounds was assessed via a food frequency questionnaire and a newly developed nutrient database. Phytoestrogen intake was not associated with breast cancer risk (odds ratio = 1.0, 95% confidence interval: 0.80, 1.3 for the highest vs. lowest quartile). Results were similar for pre- and postmenopausal women, for women in each ethnic group, and for all seven phytoestrogenic compounds studied. Phytoestrogens appear to have little effect on breast cancer risk at the levels commonly consumed by non-Asian US women: an average intake equivalent to less than one serving of tofu per week.
PMID: 11532785 [PubMed - indexed for MEDLINE]
1: Ann Pharmacother 2001 Sep;35(9):1118-21
Effects of soy phytoestrogens genistein and daidzein on breast cancer growth.
de Lemos ML.
OBJECTIVE: To determine whether genistein and daidzein, the major phytoestrogens in soy, can stimulate breast cancer growth. DATA SYNTHESIS: Systematic search through primary English-language literature on MEDLINE (1966-January 2001), EMBASE (1982-January 2001) and Current Contents (1998-January 2001). DATA SOURCES: Genistein and daidzein at low concentrations were found to stimulate breast tumor growth in in vitro and in vivo animal studies, and antagonize the antitumor effect of tamoxifen in vitro. At high concentrations, genistein inhibited tumor growth and enhanced the effect of tamoxifen in vitro. CONCLUSIONS: Genistein and daidzein may stimulate existing breast tumor growth and antagonize the effects of tamoxifen. Women with current or past breast cancer should be aware of the risks of potential tumor growth when taking soy products.
Publication Types: Review Review, Tutorial
PMID: 11573864 [PubMed - indexed for MEDLINE]