Epidemiological and experimental studies suggest that isoflavones may protect against breast cancer by acting as estrogen agonists or antagonists. A case-control study was conducted in southeast China in 2004–2005 to examine the association between dietary isoflavone intake and breast cancer risk by estrogen receptor (ER) and progesterone receptor (PR) status. The incident cases were 756 female patients with histologically confirmed breast cancer. The 1,009 age-matched controls were healthy women randomly recruited from outpatient breast clinics. We assessed isoflavone intake by face-to-face interview using a validated and reliable food-frequency questionnaire and obtained tumor ER and PR status from pathologic reports. Compared with women in the lowest intake quartiles, those in the highest quartile of total isoflavone intake had a reduced risk of all receptor status subtypes of breast cancer with a dose-response relationship. The adjusted ORs (95% CIs) were 0.39 (0.27–0.58) for ER+, 0.32 (0.21–0.49) for ER−, 0.43 (0.29–0.64) for PR+, and 0.30 (0.19–0.45) for PR− (P for trend <0.001). These inverse associations existed in both pre- and post-menopausal women after stratification. Stronger evidence of a protective effect of high isoflavone intake was observed for breast cancer tumors with concordant rather than discordant receptor status; i.e., those with ER+/PR+ (OR 0.39, 0.26–0.59) and ER−/PR− (OR 0.28, 0.17–0.44). The finding that isoflavones protect against all tumor subtypes of breast cancer have biological plausibility, being supported by evidence from experimental studies. Future studies are required to fully understand the complex regulation of isoflavone on breast cancer by tumor hormone status.
Breast cancer Dietary isoflavones Estrogen receptor Progesterone receptor
This is a preview of subscription content, log in to check access.
The authors acknowledge with gratitude the participation of the Chinese women as subjects. We are grateful for the collaboration received from the participating hospitals and their staff. The first author is supported through a postdoctoral fellowship from the National Health and Medical Research Council (Australia, ID 303292).
Shu XO, Jin F, Dai Q et al (2001) Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 10:483–488PubMedGoogle Scholar
Iwasaki M, Inoue M, Otani T et al (2008) Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-based prospective study group. J Clin Oncol 26:1677–1683. doi:10.1200/JCO.2007.13.9964CrossRefPubMedGoogle Scholar
Trock BJ, Hilakivi-Clarke L, Clarke R (2006) Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst 98:459–471PubMedCrossRefGoogle Scholar
Zava DT, Dollbaum CM, Blen M (1998) Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 217:369–378PubMedGoogle Scholar
Tham DM, Gardner CD, Haskell WL (1998) Clinical review 97: potential health benefits of dietary phytoestrogens: a review of the clinical, epidemiological, and mechanistic evidence. J Clin Endocrinol Metab 83:2223–2235. doi:10.1210/jc.83.7.2223CrossRefPubMedGoogle Scholar
Hwang CS, Kwak HS, Lim HJ et al (2006) Isoflavone metabolites and their in vitro dual functions: they can act as an estrogenic agonist or antagonist depending on the estrogen concentration. J Steroid Biochem Mol Biol 101:246–253. doi:10.1016/j.jsbmb.2006.06.020CrossRefPubMedGoogle Scholar
Lu LJ, Anderson KE, Grady JJ et al (2000) Decreased ovarian hormones during a soya diet: implications for breast cancer prevention. Cancer Res 60:4112–4121PubMedGoogle Scholar
Vanden Berghe W, Dijsselbloem N et al (2006) Attenuation of mitogen- and stress-activated protein kinase-1-driven nuclear factor-kappaB gene expression by soy isoflavones does not require estrogenic activity. Cancer Res 66:4852–4862. doi:10.1158/0008-5472.CAN-05-2957CrossRefGoogle Scholar
Lavigne JA, Takahashi Y, Chandramouli GV et al (2008) Concentration-dependent effects of genistein on global gene expression in MCF-7 breast cancer cells: an oligo microarray study. Breast Cancer Res Treat 110:85–98. doi:10.1007/s10549-007-9705-6CrossRefPubMedGoogle Scholar
Hedelin M, Löf M, Olsson M et al (2008) Dietary phytoestrogens are not associated with risk of overall breast cancer but diets rich in coumestrol are inversely associated with risk of estrogen receptor and progesterone receptor negative breast tumors in Swedish women. J Nutr 138:938–945PubMedGoogle Scholar
Institute of Nutrition, Food Hygiene, Chinese Academic of Preventive Medicine (1999) Food composition table (National Representative Values), 1st edn. People’s Health Press, BeijingGoogle Scholar
United States Department of Agriculture (2008) USDA database for the isoflavone content of selected foods. Release 2.0. Nutrient data laboratory home page. http://www.ars.usda.gov/nutrientdata/isoflav. Accessed 15 Jan 2009
Kramer F, Johnson IT, Doleman JF et al (2008) A comparison of the effects of soya isoflavonoids and fish oil on cell proliferation, apoptosis and the expression of oestrogen receptors alpha and beta in the mammary gland and colon of the rat. Br J Nutr 12:1–8. doi:10.1017/S0007114508137862Google Scholar
Low YL, Taylor JI, Grace PB et al (2005) Phytoestrogen exposure correlation with plasma estradiol in postmenopausal women in European prospective investigation of cancer and nutrition-norfolk may involve diet-gene interactions. Cancer Epidemiol Biomarkers Prev 14:213–320PubMedGoogle Scholar
Low YL, Dunning AM, Dowsett M et al (2007) Phytoestrogen exposure is associated with circulating sex hormone levels in postmenopausal women and interact with ESR1 and NR1I2 gene variants. Cancer Epidemiol Biomarkers Prev 16:1009–1016. doi:10.1158/1055-9965.EPI-06-0899CrossRefPubMedGoogle Scholar
Verkasalo PK, Appleby PN, Allen NE et al (2001) Soya intake and plasma concentrations of daidzein and genistein: validity of dietary assessment among eighty British women (Oxford arm of the European prospective investigation into cancer and nutrition). Br J Nutr 86:415–421. doi:10.1079/BJN2001424CrossRefPubMedGoogle Scholar
Maskarinec G, Singh S, Meng L et al (1998) Dietary soy intake and urinary isoflavone excretion among women from a multiethnic population. Cancer Epidemiol Biomarkers Prev 7:613–619PubMedGoogle Scholar