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Phytoestrogens and Breast Cancer Risk

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Abstract

Phytoestrogens are natural plant substances. The three main classes are isoflavones, coumestans, and lignans. Phytoestrogens have anticarcinogenic potential, but they have also significant estrogenic properties. For an evaluation of the effect of phytoestrogens on breast cancer risk we reviewed the analytical epidemiological data. A total of 18 studies were included [1–18]. Up to now, there are 13 studies that have assessed the direct relation between the individual dietary intake of soy products and the risk of breast cancer [1–13]. Overall, results do not show protective effects, with the exception maybe for women who consume phytoestrogens at adolescence or at very high doses [5, 7, 8]. Only four of these 13 studies are prospective, and none of them found statistically significant breast cancer reductions. Four studies assessed urinary isoflavones excretion in relation to breast cancer [14–17]. Three of these are case control studies [14–16], where excretion was measured after breast cancer occurrence and thus seriously limiting causal interpretation of the results. The only prospective study with urinary measurements before breast cancer occurrence was done in a Dutch postmenopausal population and showed a non-significant breast cancer risk reduction for high excretion [17]. Three studies measured enterolactone (lignan): two case control studies reported a preventive effect on breast cancer risk [14, 18], but the only prospective study did not [17]. In conclusion, few prospective studies (n = 5) were done to assess the effects of phytoestrogens on breast cancer risk. None of them found protective effects. However, these prospective studies did not focus on ‘age at consumption’, which seems to be important based on results from dietary case control studies done so far.

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References

  1. Hirohata T, Shigematsu T, Nomura AMY, Nomura Y, Horie A, Hirohata I: Occurrence of breast cancer in relation to diet and reproductive history: a case control study in Fukuoka, Japan. Natl Cancer Institute Monogr 69: 187-190, 1985

    Google Scholar 

  2. Lee HP, Gourley L, Duffy SW, Esteve J, Lee J, Day NE: Dietary effects on breast cancer risk in Singapore. Lancet 331: 1197-1200, 1991

    Google Scholar 

  3. Hirose K, Tajima K, Hamajima N, Inoue M, Takezaki T, Kuroishi T, Yoshida M, Tokudome S: A large-scale, hospitalbased case-control study of risk factors for breast cancer according to menopausal status. Jpn J Cancer Res 86: 146-154, 1995

    Google Scholar 

  4. Yuan JM, Wang QS, Ross RK, Henderson BE, Yu MC: Diet and breast cancer in Shanghai and Tianjin, China. Br J Cancer 71: 1353-1358, 1995

    Google Scholar 

  5. Wu AH, Ziegler RG, Horn-Ross PL, Nomura AMY, West DW, Kolonel LN, Rosenthal JF, Hoover RN, Pike MC: Tofu and risk of breast cancer in Asian-Americans. Cancer Epidemiol Biomarkers Prev 5: 901-906, 1996

    Google Scholar 

  6. Witte JS, Ursin G, Siemiatycki J, Thompson WD, Paganini-Hill A, Haile RW: Diet and premenopausal bilateral breast cancer: a case-control study. Breast Cancer Res Treat 42: 243-251, 1997

    Google Scholar 

  7. Shu XO, Jin F, Dai Q, Wen W, Potter JD, Kushi LH, Ruan Z, Gao YT, Zheng W: Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 10: 483-488, 2001

    Google Scholar 

  8. Dai Q, Shu X-O, Jin F, Potter JD, Kushi LH, Teas J, Gao Y-T, Zheng W: Population based case control study of soyfood intake and breast cancer risk in Shanghai. Br J Cancer 85: 372-378, 2001

    Google Scholar 

  9. Horn-Ross PL, John EM, Lee M, Stewart SL, Koo J, Sakoda LC, Shiau AC, Goldstein J, Davis P, Perez-Stable EJ: Phytoestrogen consumption and breast cancer risk in a multiethnic population: the Bay Area Breast Cancer Study. Am J Epidemiol 154: 434-441, 2001

    Google Scholar 

  10. Nomura A, Henderson BE, Lee J: Breast cancer and diet among the Japanese in Hawaii. Am J Clin Nutr 31: 2020-2025, 1978

    Google Scholar 

  11. Hirayama T: Life-style and mortality: a large scale censusbased cohort study in Japan. In: Wahrendorf J (ed) Contributions to Epidemiology and Biostatistics. Vol 6, Karger, Basel, 1990

    Google Scholar 

  12. Greenstein J, Kushi L, Zheng W, Fee R, Campbell D, Sellers T, Folsom A: Risk of breast cancer associated with intake of specific foods and food groups. Am J Epidemiol 145: S36, 1996

    Google Scholar 

  13. Key TJ, Sharp GB, Appleby PN, Beral V, Goodman MT, Soda M, Mabuchi K: Soya foods and breast cancer risk: a prospective study in Hiroshima and Nagasaki, Japan. Br J Cancer 81: 1248-1256, 1999

    Google Scholar 

  14. Ingram D, Sanders K, Kolybaba M, Lopez D: Case-control study of phyto-oestrogens and breast cancer. Lancet 350: 990-994, 1997

    Google Scholar 

  15. Zheng W, Dai Q, Custer LJ, Shu X-O, Wen W-Q, Jin F, Franke AA: Urinary excretion of isoflavonoids and the risk of breast cancer. Cancer Epidemiol Biomarkers Prev 8: 35-40, 1999

    Google Scholar 

  16. Murkies A, Dalais FS, Briganti EM, Burger HG, Healy DL, Wahlqvist ML, Davis SR: Phytoestrogens and breast cancer in postmenopausal women: a case control study. Menopause 7: 289-296, 2000

    Google Scholar 

  17. Tonkelaar den I, Keinan-Boker L, Veer van't P, Arts CJM, Adlercreutz H, Thijssen JHH, Peeters PHM: Urinary phytooestrogens and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev 10: 223-228, 2001

    Google Scholar 

  18. Pietinen P, Stumpf K, Mannisto S, Kataja V, Uusitupa M, Adlercreutz H: Serum enterolactone and the risk of breast cancer. A case control study in Eastern Finland. Cancer Epidemiol Biomarkers Prev 10: 339-344, 2001

    Google Scholar 

  19. Setchell KDR, Adlercreutz H: Mammelian lignans and phytoestrogens. In: Rowland I (ed) The Role of the Gut Flora in Toxicity and Cancer, Academic Press, London, 1988, pp 315-346

    Google Scholar 

  20. Setchell KDR, Borriello SP, Hulme P, Axelson M: Nonsteroidal estrogens of dietary origin: possible roles in hormonedependent disease. Am J Clin Nutr 40: 569-578, 1984

    Google Scholar 

  21. Thompson LU, Robb P, Serraino M, Cheung F: Mammalian lignan production from various foods. Nutr Cancer 16: 43-52, 1991

    Google Scholar 

  22. Shutt DA: The effects of plant oestrogens in animal reproduction. Endeavour 35: 110-113, 1976

    Google Scholar 

  23. Setchell KDR, Gosselin SJ, Welsh MB, Johnston JO, Balistreri WF, Kramer LW, Dressner BL, Tart MJ: Dietary estrogens-a probable cause of infertility and liver disease in captive cheetah. Gastroenterology 93: 225-233, 1987

    Google Scholar 

  24. Adlercreutz H, Fotsis T, Heikkinen R, Dwyer JT, Woods M, Goldin BR, Gorbach SL: Excretion of the lignans enterolactone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women and in women with breast cancer. Lancet II: 1295-1299, 1982

    Google Scholar 

  25. Adlercreutz H: Western diet and Western diseases: some hormonal and biochemical mechanisms and associations. Scand J Clin Lab Inv 50(S201): 3-23, 1990

    Google Scholar 

  26. Adlercreutz H, Markkanen H, Watanabe S: Plasma concentrations of phyto-estrogens in Japanese men. Lancet 342: 1209-1210, 1993

    Google Scholar 

  27. Messina M, Barnes S: The role of soy products in reducing risk of cancer. JNCI 83: 541-546, 1991

    Google Scholar 

  28. Messina MJ, Persky V, Setchell KDR, Barnes S: Soy intake and cancer risk: a review of in vitro and in vivo data. Nutr Cancer 21: 113-131, 1994

    Google Scholar 

  29. Kuiper GGJM, Carlsson B, Grandien K, Enmark E, Haggblad J, Nilsson S, Gustafsson JA: Comparison of the ligand binding specificity and transcript tissue distribution of estrogen receptors alpha and beta. Endocrinol 138: 863-870, 1997

    Google Scholar 

  30. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. JNCI 90: 1371-1388, 1998

    Google Scholar 

  31. Early Breast Cancer Trialists' Collaborative Group. Tamoxifen for early breast cancer: an overview of randomised trials. Lancet 351: 1451-1467, 1998

    Google Scholar 

  32. Powles T, Eeles R, Ashley S, Easton D, Chang J, Dowsett M, Tidy A, Viggers J, Davey J: Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 352: 98-101, 1998

    Google Scholar 

  33. Peterson G: Evaluation of the chemical targets of genistein in tumour cells. J Nutr 125: 784S-789S, 1995

    Google Scholar 

  34. Fotsis T, Pepper M, Adlercreutz H, Fleischmann G, Hase T, Montesano R, Schweigerer L: Genistein, a dietary derived inhibitor of in vitro angiogenesis. Proc Nat Acad Sci USA 90: 2690-2694, 1993

    Google Scholar 

  35. Barnes S, Grubbs, Setchell KDR, Carlson J: Soybeans inhibit mammary tumors in models of breast cancer. In: Pariza MW, Aeschbacher H-U, Felton JS, Sato S (eds) Mutagens and Carcinogens in the Diet. Wiley Liss, New York, 1990, pp 239-253

    Google Scholar 

  36. Martini MC, Dancisak BB, Haggans CJ, Thomas W, Slavin JL: Effects of soy intake on sex hormone metabolism in premenopausal women. Nutr Cancer 34: 133-139, 1999

    Google Scholar 

  37. Nagata C, Takatsuka N, Inaba S, Kawakami N, Shimizu H: Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women. J Natl Cancer Inst 90: 1830-1835, 1998

    Google Scholar 

  38. Lu L-JW, Anderson KE, Grady JJ, Kohen F, Nagamani M: Decreased ovarian hormones during a soya diet: implications for breast cancer prevention. Cancer Res 60: 4112-4121, 2000

    Google Scholar 

  39. Duncan AM, Merz BE, Xu X, Nagel TC, Phipps WR, Kurzer MS: Soy isoflavones exert modest hormonal effects in premenopausal women. J Clin Endocrinol Metab 84: 192-197, 1999

    Google Scholar 

  40. Xu X, Duncan AM, Merz BE, Kurzer MS: Effects of soy isoflavones on estrogen and phytoestrogen metabolism in premenopausal women. Cancer Epidemiol Biomarkers Prev 7: 1101-1108, 1998

    Google Scholar 

  41. Lu L-JW, Cree M, Josyula S, Nagamani M, Grady JJ, Anderson KE: Increased urinary excretion of 2-hydroxyestrone but not 16 alfa-hydroxyestrone in premenopausal women during soya diet containing isoflavones. Cancer Res 60: 1299-1305, 2000

    Google Scholar 

  42. Xu X, Duncan AM, Wangen KE, Kurzer MS: Soy consumption alters endogenous estrogen metabolism in postmenopausal women. Cancer Epidemiol Biomarkers Prev 9: 781-786, 2000

    Google Scholar 

  43. Haggans CJ, Travelli EJ, Thomas W, Martini MC, Slavin JL: The effect of flaxseed and wheat bran consumption on urinary estrogen metabolites in premenopausal women. Cancer Epidemiol Biomarkers Prev 9: 719-725, 2000

    Google Scholar 

  44. Haggans CJ, Hutchins AM, Olson BA, Thomas W, Martini MC, Slavin JL: Effect of flaxseed consumption on urinary estrogen metabolites in postmenopausal women. Nutr Cancer 33: 188-195, 1999

    Google Scholar 

  45. Petrakis NL, Barnes S, King EB, Lowenstein J, Wiencke J, Lee MM, Miike R, Kirk M, Coward L: Stimulatory influence of soy protein isolate on breast secretion in pre-and postmenopausal women. Cancer Epidemiol Biomarkers Prev 5: 785-794, 1996

    Google Scholar 

  46. Bingham SA, Atkinson C, Liggins J, Bluck L, Coward A: Review article. Phyto-oestrogens: where are we now? Br J Nutr 79: 393-406, 1998

    Google Scholar 

  47. Messina MJ: Legumes and soybeans: overview of their nutritional profiles and health effects. Am J Clin Nutr 70: 439S-450S, 1999

    Google Scholar 

  48. Bouker KB, Hilakivi-Clarke L: Genistein: does it prevent or promote breast cancer. Environ Health Persp 108: 701-708, 2000

    Google Scholar 

  49. Strom BL, Schinnar R, Ziegler EE, Barnhart KT, Sammel MD, Macones GA, Stallings VA, Drulis JM, Nelson SE, Hanson FN: Exposure to soy-based formula in infancy and endocrinological and reproductive outcomes in young adulthood. JAMA 286: 807-814, 2001

    Google Scholar 

  50. Goldman LR, Newbold R, Swan SH: Exposure to soybased formula in infancy. JAMA (letter) 286: 2402-2403, 2001

    Google Scholar 

  51. Thomas HV, Reeves GK, Key TJ: Endogenous estrogen and postmenopausal breast cancer: a quantitative review. Cancer Causes Control 8: 922-928, 1997

    Google Scholar 

  52. Key TJ: Serum oestradiol and breast cancer risk. Endocr Relat Cancer 6: 175-180, 1999

    Google Scholar 

  53. Clemons M, Goss P: Estrogen and the risk of breast cancer. N Engl J Med 344: 276-285, 2001

    Google Scholar 

  54. Kilkkinen A, Stumpf K, Pietinen P, Valsta LM, Tapanainen H, Adlercreutz H: Determinants of serum enterolactone concentration. Am J Clin Nutr 73: 1094-1100, 2001

    Google Scholar 

  55. Horner NK, Kristal AR, Prunty J, Skor HE, Potter JD, Lampe JW: Dietary determinants of plasma enterolactone. Cancer Epidemiol Biomarkers Prev 11: 121-126, 2002

    Google Scholar 

  56. Wu AH, Ziegler RG, Nomura AMW, West DW, Kolonel LN, Horn-Ross PL, Hoover RN, Pike MC: Soy intake and risk of breast cancer in Asians and Asian Americans. Am J Clin Nutr 68: 1437S-1443S, 1998

    Google Scholar 

  57. Adlercreutz H, Mousavi Y, Hockerstedt K: Diet and breast cancer. Acta Oncol 31: 175-181, 1992

    Google Scholar 

  58. Treloar AE, Boynton RE, Behn BG, Brown BW: Variation of the human menstrual cycle throughout life. Int J Fertil 12: 77-126, 1976

    Google Scholar 

  59. Goldin BR, Adlercreutz H, Gorbach SL, Woods MN, Dweyer JT, Conlon T, Bohn E, Gerrshoff SN: The relationship between estrogen levels and diets of Caucasian American and Oriental immigrant women. Am J Clin Nutr 44: 945-953, 1986

    Google Scholar 

  60. Key TJ, Chen J, Pike MC, Boreham J: Sex hormones in women in rural China and Britain. Br J Cancer 62: 631-636, 1990

    Google Scholar 

  61. Lee HP, Gourley L, Duffy SW, Esteve J, Lee J, Day NE: Risk factors for breast cancer by age and menopausal status: a case-control study in Singapore. Cancer Causes Control 3: 313-322, 1992

    Google Scholar 

  62. Pillow PC, Duphorne CM, Chang S, Contois JH, Strom SS, Spitz MR, Hursting SD: Development of a database for assessing dietary phytoestrogen intake. Nutr Cancer 33: 3-19, 1999

    Google Scholar 

  63. Horn-Ross PL, Barnes S, Lee M, Coward L, Mandel JE, Koo J, John EM, Smith M: Assessing phytoestrogen exposure in epidemiologic studies: development of a database (United States). Cancer Causes Control 11: 289-298, 2000

    Google Scholar 

  64. Setchell KD, Lawson AM, Borriello SP, Harkness R, Gordon H, Morgan DM, Kirk DN, Adlercreatz H, Anderson LC, Axelson M: Lignan formation in man-microbial involvement and possible roles in relation to cancer. Lancet II: 4-7, 1981

    Google Scholar 

  65. Setchell KDM, Borriello SP, Hulme P, Axelson M: Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Am J Clin Nutr 40: 569-578, 1984

    Google Scholar 

  66. Kelly GE, Joannou GE, Reeder AY, Nelson C, Waring MA: The variable metabolic response to dietary isoflavones in humans. Proc Soc Exp Biol Med 208: 40-43, 1995

    Google Scholar 

  67. Axelson M, Sjovall J, Gutafsson BE, Setchel KD: Soya: a dietary source of the non-steroidal estrogen equol in man and animals. J Endocrinol 102: 49-56, 1984

    Google Scholar 

  68. Karr SC, Lampe AM, Slavin JL: Urinary isoflavonoid excretion in human dose-dependent at low to moderate levels of soy protein consumption. Am J Clin Nutr 66: 46-51, 1997

    Google Scholar 

  69. Chen Z, Zheng W, Custer LJ, Dai Q, Shu XO, Jin F, Franke AA: Usual dietary consumption of soy foods and its correlation with the excretion rate of isoflavones in overnight urine samples among Chinese women in Shanghai. Nutr Cancer 33: 82-87, 1999

    Google Scholar 

  70. Tesarik J, Mendoza C: Phyto-oestrogens and breast cancer. Lancet 351: 138; discussion 138-139, 1998

    Google Scholar 

  71. Humfrey C: Phyto-oestrogens and breast cancer. Lancet 351: 138; discussion 138-139, 1998

    Google Scholar 

  72. de Souza RM: Phyto-oestrogens and breast cancer. Lancet 351: 137-138; discussion 138-139, 1998

    Google Scholar 

  73. Mangtani P, Silva ID: Phyto-oestrogens and breast cancer. Lancet 351: 137; discussion 138-139, 1998

    Google Scholar 

  74. Heaton KW, Lewis SJ: Phyto-oestrogens and breast cancer. Lancet 351: 137; discussion 138-139, 1998

    Google Scholar 

  75. Messina M, Barnes S, Setchell KD: Phyto-oestrogens and breast cancer. Lancet 350: 971-972, 1997

    Google Scholar 

  76. Smith-Warner SA, Spiegelman D, Yaun SS, Adami HO, Beeson WL, van den Brandt PA, Folsom AR, Fraser GE, Freudenheim JL, Goldbohm RA, Graham S, Miller AB, Potter JD, Rohan TE, Speizer FE, Toniolo P, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Hunter DJ: Intake of fruit and vegetables and risk of breast cancer: a pooled analysis of cohort studies. JAMA 285: 769-776, 2001

    Google Scholar 

  77. Mazur WM, Wahala K, Rasku S, Salakka A, Hase T, Adlercreutz H: Lignan and isoflavonoid concentrations in tea and coffee. Br J Nutr 79: 37-45, 1997

    Google Scholar 

  78. Lampe JW, Gustafsson DR, Hutchins AM, Martini MC, Li S, Wahala K, Grandits GA, Potter J, Slavin J: Urinary isoflavonoid and lignan excretion on a Western diet: relation to soy, vegetable, and fruit intake. Cancer Epidemiol Biomarkers Prev 8: 699-707, 1999

    Google Scholar 

  79. This P, de la Rochefordiere A, Clough K, Fourquet A, Magdelenat H: The Breast Cancer Group of the Institut Curie: Phytoestrogens after breast cancer. Endocr-Relat Cancer 8: 129-134, 2001

    Google Scholar 

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  1. Julius Center for Health Studies and Primary Care, University Medical Center Utrecht, The Netherlands

    P.H.M. Peeters, L. Keinan-Boker, Y.T. van der Schouw & D.E. Grobbee

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Peeters, P., Keinan-Boker, L., van der Schouw, Y. et al. Phytoestrogens and Breast Cancer Risk. Breast Cancer Res Treat 77, 171–183 (2003). https://doi.org/10.1023/A:1021381101632

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