The safety of application and the benefits of isoflavones for postmenopausal women were the focus of a symposium organised by the CRN (Council for Responsible Nutrition), which took place on the 13th and 14th of May 2009 in Milan (Italy) under active participation of the EFSA (European Food Safety Authority).
In addition to the lack of evidence pointing to breast cancer promoting effects by isoflavones, Prof. Dr. Xiao Ou Shu from the Vanderbilt University (Nashville, USA) clinically demonstrated life-prolonging effects of the intake of isoflavones in breast cancer patients and the benefit of the combination of tamoxifen and isoflavones (Shu 2009). Breast cancer is one of the most frequent cancer types in Western industrialized nations. With the currently established therapy the five-year survival rate is relatively high, with 89 % (Nasr et al. 2009). However, in 10-15 % of women there is a recurrence of cancer within three years. 69 % of women treated with tamoxifen suffer from typical menopausal symptoms such as hot flushes or night sweats (Dorjgochoo et al. 2009).
The published literature contains randomized trials, where the daily intake of 36 to 120 mg of isoflavones over periods of up to three years had no negative effect on biomarkers of breast cancer (Burke et al. 2003; Cheng et al. 2007; Hargreaves et al. 1999; Kaari et al. 2006; Marini et al. 2008; Maskarinec et al. 2009; Nahas et al. 2007; Powles et al. 2008; Qin et al. 2009; Verheus et al. 2008). There was likewise no impairment of cancer therapy in large case control studies (Boyapati et al. 2005; Fink et al. 2007). In one cohort study in 1,954 breast cancer patients there was not only a reduced rate of cancer recurrence, but also no undesired interaction with tamoxifen (Guha et al. 2009). The study explicitly mentioned positive effects against estrogen-receptor-positive breast cancer, and thus against a form of cancer which reacts very sensitively to estrogens by growth stimulation (Guha et al. 2009). In the “Shanghai Breast Cancer Survival Study” Prof. Shu made a follow-up of 5,043 women post breast-cancer therapy (Messina et al. 2009). First preliminary results after more than 5 years of this – to date – largest still ongoing trial in breast cancer patients seem to indicate a more positive prognosis in the course of the disease under exposure to soy isoflavones, with a hazard ratio associated with the highest quartile intake being 0.67 (p = 0.01; 95% CI 0.50–0.88) for disease-specific mortality or relapse compared with the lowest quartile of intake. The results, which are highly relevant to the question of the safety of isoflavones, have recently been published (Shu et al. 2009).
Further reports from the Milan 2009 Soy Safety Symposium:
1. Plant “hormones”: Guilty by association with estrogens? International Symposium in Milan on the safety and efficacy of soy
2. Facts Related to Bioavailability
3. Lack of relevance of animal models for an extrapolation of risks of isoflavones
4. Isoflavones protect „menopausal” mice from breast cancer
5. Breast cancer risk is increased by synthetic gestagens
6. Breast tissue density remains unaltered with soy
7. Clinical studies demonstrate safety of soy in the breast
8. Study in more than 5,000 breast cancer patients: First positive tendencies with soy!
9. No effects of isoflavones on the endometrium
10. Isoflavones also safe at the thyroid gland
11. Backgrounds on Menopausal Hot Flushes
12. Clinical safety of isoflavone-containing preparations
13. Clinical effects of isoflavones against menopausal hot flushes
References
Boyapati SM, Shu XO, Ruan ZX, Dai Q, Cai Q, Gao YT and Zheng W (2005). Soyfood intake and breast cancer survival: a followup of the Shanghai Breast Cancer Study. Breast Cancer Res Treat 92(1):11-17.
Burke GL, Legault C, Anthony M, Bland DR, Morgan TM, Naughton MJ, Leggett K, Washburn SA and Vitolins MZ (2003). Soy protein and isoflavone effects on vasomotor symptoms in peri- and postmenopausal women: the Soy Estrogen Alternative Study. Menopause 10(2):147-153.
Cheng G, Wilczek B, Warner M, Gustafsson JA and Landgren BM (2007). Isoflavone treatment for acute menopausal symptoms. Menopause 14(3 Pt 1):468-473.
Dorjgochoo T, Gu K, Kallianpur A, Zheng Y, Zheng W, Chen Z, Lu W and Shu XO (2009). Menopausal symptoms among breast cancer patients 6 months after diagnosis: a report from the Shanghai Breast Cancer Survival Study. Menopause 16(6): 1205-1212.
Fink BN, Steck SE, Wolff MS, Britton JA, Kabat GC, Gaudet MM, Abrahamson PE, Bell P, Schroeder JC, Teitelbaum SL, Neugut AI and Gammon MD (2007). Dietary Flavonoid Intake and Breast Cancer Survival among Women on Long Island. Cancer Epidemiol Biomarkers Prev 16(11):2285-2292.
Guha N, Kwan ML, Quesenberry CP, Jr., Weltzien EK, Castillo AL and Caan BJ (2009). Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast Cancer Res 118(2): 395-405.
Hargreaves DF, Potten CS, Harding C, Shaw LE, Morton MS, Roberts SA, Howell A and Bundred NJ (1999). Two-week dietary soy supplementation has an estrogenic effect on normal premenopausal breast. J Clin Endocrinol Metab 84(11):4017-4024.
Kaari C, Haidar MA, Junior JM, Nunes MG, Quadros LG, Kemp C, Stavale JN and Baracat EC (2006). Randomized clinical trial comparing conjugated equine estrogens and isoflavones in postmenopausal women: a pilot study. Maturitas 53(1):49-58.
Marini H, Bitto A, Altavilla D, Burnett BP, Polito F, Di Stefano, V, Minutoli L, Atteritano M, Levy RM, D'Anna R, Frisina N, Mazzaferro S, Cancellieri F, Cannata ML, Corrado F, Frisina A, Adamo V, Lubrano C, Sansotta C, Marini R, Adamo EB and Squadrito F (2008). Breast Safety and efficacy of genistein aglycone for post-menopausal bone loss: A follow-up study. J Clin Endocrinol Metab 93(12):7487-7496.
Maskarinec G, Verheus M, Steinberg FM, Amato P, Cramer MK, Lewis RD, Murray MJ, Young RL and Wong WW (2009). Various Doses of Soy Isoflavones Do Not Modify Mammographic Density in Postmenopausal Women. J Nutr 139:981-986.
Messina M, Watanabe S and Setchell KD (2009). Report on the 8th International Symposium on the Role of Soy in Health Promotion and Chronic Disease Prevention and Treatment. J Nutr 139(4):796S-802S.
Nahas EAP, Nahas-Neto J, Orsatti FL, Carvalho EP, Oliveira ML and Dias R (2007). Efficacy and safety of a soy isoflavone extract in postmenopausal women: A randomized, double-blind, and placebo-controlled study. Maturitas 58(3):249-258.
Nasr E, Nasr D, Azoury F and Fares G (2009). Outcome and prognostic factors in the conservative treatment of breast cancer. J Med Liban 57(2):130-134.
Powles TJ, Howell A, Evans DG, McCloskey EV, Ashley S, Greenhalgh R, Affen J, Flook LA and Tidy A (2008). Red clover isoflavones are safe and well tolerated in women with a family history of breast cancer. Menopause Int 14(1):6-12.
Qin W, Zhu W, Shi H, Hewett JE, Ruhlen RL, MacDonald RS, Rottinghaus GE, Chen YC and Sauter ER (2009). Soy isoflavones have an antiestrogenic effect and alter mammary promoter hypermethylation in healthy premenopausal women. Nutr Cancer 61(2):238-244.
Shu XO (2009). Soyfood consumption and breast cancer prognosis: Review of the epidemiologic data. Symposium on Evaluating the Efficacy and Safety of Isoflavones for Postmenopausal Women, 13-14 May. Milan (Italy): Council for Responsible Nutrition.
Shu XO, Zheng Y, Cai H, Gu K, Chen Z, Zheng W and Lu W (2009). Soy intake and breast cancer survival. JAMA 302(22):2437-2443.
Verheus M, van Gils CH, Kreijkamp-Kaspers S, Kok L, Peeters PH, Grobbee DE and van der Schouw YT (2008). Soy protein containing isoflavones and mammographic density in a randomized controlled trial in postmenopausal women. Cancer Epidemiol Biomarkers Prev 17(10):2632-2638.
Cancer 