1 / 31

Isoflavonoids and Breast Cancer Risk

Explore the structure, sources, and health effects of isoflavonoids on breast cancer risk through various study types and recommendations for soy intake across different risk profiles.

emiliat
Download Presentation

Isoflavonoids and Breast Cancer Risk

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Isoflavonoids and Breast Cancer Risk Michelle D. Holmes, MD, DrPH michelle.holmes@channing.harvard.edu

  2. Learning Objectives • To understand the structure and food sources of isoflavonoids • To understand the different types of research studies supporting an isoflavonoid-breast cancer link • To understand recommendations for soy intake for average risk women and also for women with a personal or family history of breast cancer

  3. Performance Objectives • Students should be able to evaluate new research findings on isoflavonoids and breast cancer in light of the previous evidence • Be able to make recommendations on soy intake for average risk and high risk women based on the weight of present research evidence

  4. Interests I was trained as a primary care physician and have always had a strong interest in public health. I have always been interested in the impact of diet, exercise, and other lifestyle factors on chronic disease. I became an epidemiologist in mid career. My research focus is diet and cancer.

  5. Overview • Structure, food sources of isoflavonoids • Different types of studies supporting a isoflavonoid-breast cancer link • international • in vitro and animal • case-control and cohort • trials • Recommendations

  6. Structure and Food Sources • Flavonoids are plant-derived polyphenols • Isoflavonoid subgroup weakly estrogenic • examples: genistein, daidzein, equol

  7. Structure of Isoflavonoids and Estradiol Messina, Nutr Cancer 1994;21:113

  8. Intake • 1 gram soybeans  2 mg isoflavonoids • Typical daily intake: • Asian countries  50-100 mg • Western countries  <1 mg

  9. International Data • Asian countries: high soy intake and lower breast cancer rates • Japanese migrants assume host country rates of breast cancer • Western diet: minimal soy • Vegetarians in the US have lower cancer rates

  10. EstrogenicEffects • Weakly estrogenic 1/1000th -1/100,000th the strength of estradiol • Produce estrogenic responses in mice • May be antagonistic by competing for estrogen receptors

  11. What is the evidence that isoflavonoids prevent breast cancer?

  12. In vitro studies of Genistein • Inhibits Tyrosine Kinase (important for cell proliferation, transformation) Markovits J, 1989, Cancer Res Linnasier C, 1993, Biochemical Pharmacology • Inhibits DNA topoisomerase II (causes DNA breaks) Markovits J, 1989, Cancer Res

  13. In vitro Studies of Genistein • Induces Differentiation Constantinou A, 1990, Cancer Res Kando K, 1991, Cancer Res Watanabe T, 1993, Cancer Res • Inhibits Angiogenesis Fotis T, 1993, Proc Natl Acad Sci

  14. Genistein as an Angiogenesis Inhibitor 5 4 3 Length, mm 2 1 0 bFGF, µg/L 0 30 30 30 30 genistein, µmol/L 0 0 50 100 200 Fotsis,J. Nutr 1995,125;790S

  15. In vitro Studies of Genistein • Affects Growth of ER+ human breast cancer cells: • Stimulates at low dose • Inhibits at high dose Miodini P, 1999, Br J Cancer Nakagawa H, 2000, J Cancer Res Clin Oncol • Inhibits growth of ER- human breast cancer cells Shen F, 1999, Anticancer Res

  16. Animal Studies: Isoflavonoids and Mammary Tumors Study ResultsStudy Results Carroll, 1975 Null Barnes, 1990  Troll, 1980  Barnes, 1990  Gridley, 1983 Null Constantinou 1998  Hawrylewics, 1989  Fritz, 1998  Hsueh, 1989 Null Hilakivi-Clarke 1999  Baggott, 1990  Hakkak, 2000  Santell, 2000 Null

  17. Mammary Tumor Incidence in Rats Casein SPI+Met SPI Percent of rats with mammary tumors Weeks after NMU administration 100 Casein NMU INJECTION DIET CHANGE 10 8 0 5 26

  18. Adolescent Soy Intake and Breast Cancer RiskShu, CEBP 2001 • 1459 cases and 1556 controls in China • Diet age 13-15 by interview • Separately asked mothers of 296 cases and 359 controls

  19. Adolescent Diet Quintile of IntakeRR95% CI 1 1.00 - Total 2 0.75 (0.60-0.93) soy 3 0.69 (0.55-0.87) foods 4 0.69 (0.55-0.86) 5 0.51 (0.41-0.65) p-trend <0.01

  20. Cohort Studies of Soy and Breast Cancer Reference Populations Cases ExposureRR Nomura, 1978 Japanese in HI 86 Husbands diet Null Hirayama, 1985 Japan - miso 0.46 Key, 1999 Japan 427 tofu, miso Null

  21. Problem:Assessment of dietary isoflavonoids is difficult in epidemiological studies Amoung U.S women, large amounts of isoflavonoids come from “hidden” soy: - soy protein isolate - soy concentrate - soy flour (white bread and donuts) Frequent in processed foods and is brand-dependent Horn-Ross, CCC, 2000

  22. Trials: Does Soy Lower Estrogens? Reference N Duration: Months Result Cassidy, 1994 6 1  FSH, LH follicular E2 Duncan, 1999 14 3 FSH, LH Martini, 1999 36 2 No change Lu, 2000 8 1 shifted metabolism to more favorable estrogens metabolites Lu, 2000 10 1  progesterone levels Wu, 2000 20 7  luteal E2 only in 10 Asian women

  23. Cont’d Reference N Duration: Months Result Duncan, 2000 14 -  estrogens only in 5 equol excreters regardless of soy intake Xu, 2000 18 9 shifted metabolism to more favorable estrogen metabolites

  24. RCTs of Soy and Estrogen Nagata, 1998 Hi/Low SoyDuration/monthsResults 31/29 2 E2 and estrone but N.S

  25. Does Soy Increase Breast cell Proliferation? McMichael-Phillips, AJCN, 1998 - RCT of 48 premenopausal women scheduled for breast biopsy - 2 weeks soy supplemented diet - Normal breast tissue labelled for markers of proliferation - High soy group had  proliferation Hargreoues, J Clin Endoc Metab, 1999 - Sequential trial of 84 premenopausal women - Underwent nipple aspiration (NA) -  markers of proliferation in NA fluid after soy intake

  26. Does Soy Increase Breast cell Proliferation? Maskarinec, Br Cancer Res, 2001 - Cross-sectional study in HI - Soy intake assessed by questionnaire vs. density on mammogram -Results: - High soy  density - High soy  breast size

  27. Hypothesis: Could early-life soy exposure induce early breast maturation making it resistant to carcinogenesis? Evidence: • Isoflavonoids promote differentiation in vitro • Some animal studies have shown large effects with pre-pubertal exposure • International differences persist until 2nd generation • Shu, 2001 case-control study of adolescent soy intake

  28. Isoflavonoids and Breast Cancer Risk: Conclusions • Biologically plausible: • estrogenic effects • effects on angiogenesis, cell growth • Animal data suggestive • Epidemiologic data suggestive but cohort studies are poor • Adverse effects possible, balance between proestrogen/anti estrogen effects is unclear

  29. What should clinicians recommend? • Modest intake of soy products similar to Asian cultures (1-2 servings/day) unlikely to be harmful in the average women and may be helpful • Many clinicians, NCI website suggest that high risk women avoid soy: • Women with breast cancer, particularly ER+ or on tamoxifen • Women with a strong family history

More Related