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Cited by 40Phytoestrogen effects and researchMenopause: Health Impacts and TreatmentsCancer Risks and Factors

Use of isoflavone supplements is associated with reduced postmenopausal breast cancer risk

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Boucher, Beatrice A., Cotterchio, Michelle, Anderson, Laura N., Kreiger, Nancy, Kirsh, Victoria A., Thompson, Lilian U.·2013·International Journal of Cancer
DOI 10.1002/ijc.27769
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Abstract

Botanical supplements are widely used and contain diverse ingredients, including isoflavones. Food‐based isoflavones have been associated with reduced breast cancer risk. However, no study has comprehensively evaluated supplements identified by isoflavone content and breast cancer risk. Associations between ever use of 28 isoflavone supplements and breast cancer risk in Ontario, Canada were evaluated using cases (n = 3,101) identified in 2002–2003 from the Ontario Cancer Registry and controls (n = 3,471) identified through random digit dialing methods. Multivariate logistic regression was used to estimate age‐adjusted odds ratio (AOR) and 95% confidence intervals (CI). Several individual supplements were associated with reduced breast cancer risk (e.g., Natural HRT; AOR = 0.39; 95% CI: 0.22, 0.69; nusers = 58). Use of any isoflavone supplements was associated with reduced risk when ≥3 were ever used (AOR = 0.68; 95% CI: 0.54, 0.86; nusers = 332; ptrend = 0.008) or any was taken >5 years (AOR = 0.75; 95% CI: 0.60, 0.94; nusers = 325; ptrend = 0.01); high content supplements were consistently associated with reduced risk. Risk reduction was confined to postmenopausal breast cancer for both individual and combined supplements, and was strongest in the latter among high content users who ever took ≥3 supplements (AOR = 0.55; 95% CI: 0.38, 0.81; nusers = 118; ptrend = 0.04) or any >5 years (AOR = 0.47; 95% CI: 0.27, 0.81; nusers = 60; ptrend = 0.03). Associations did not differ by estrogen‐progesterone tumor receptor status. In conclusion, isoflavone supplements were associated with decreased postmenopausal breast cancer risk. Further research to examine these novel findings is warranted, given the low supplement use and potential limitations of our results.

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  • Of 44 case-control studies, 32 showed higher consumption of soy foods and/or soy isoflavones was associated with lower risk for primary breast cancer, breast cancer mortality, or improved markers of prognosis among the overall study population.

    “Overall, of the 44 case control studies, 32 showed that higher consumption of soy foods and/ or soy isoflavones was associated with lower risk for primary breast cancer [42-46,49-51,53,54,56-58,61-64,66,71-73,75,77-79,81,83], breast cancer mortality [55], or improved markers of prognosis (ER+ status vs receptor negative status) [74,82] among the overall study population.”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [42]

    The Discussion reports reduced breast cancer risk associated with isoflavone supplements, supporting this paper as an example in the cited list of studies on primary breast cancer risk. But the Results (p. 1441) say the significant reductions in stratified analyses remained only among postmenopausal women. This paper does not establish the sentence’s aggregate count of 32 of 44 case-control studies or its broader claim about soy-food consumption in overall study populations. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Eight of 12 (67%) studies examining high soy food or protein and six of seven (86%) studies examining high soy isoflavones reported inverse associations between soy and breast cancer risk.

    “Eight of 12 (67%) studies examining high soy food or protein [45,46,61,64,72,77,78,81] and six of seven (86%) studies examining high soy isoflavones [42,43,45,75,77,81] reported inverse associations between soy and breast cancer risk.”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [42]

    The section “Comparison with studies examining isoflavones from foods” says three meta-analyses suggest reduced breast cancer risk, including stronger inverse associations among high-isoflavone consumers. It also says individual study results are inconsistent. It does not report the claimed counts of 8 of 12 soy food or protein studies and 6 of 7 soy isoflavone studies, or their percentages. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Among case-control studies reporting odds ratios with confidence intervals, nine of 16 (56%) showed a significant inverse relationship between soy isoflavone intake and breast cancer risk.

    “Of the 16 studies, nine (56%) showed a significant inverse relationship between soy isoflavone intake and risk of breast cancer [42,43,45,48,49,63,75,77,81].”

    From Soy, Red Clover, and Isoflavones and Breast Cancer: A Systematic Review (2013) · cites this paper as [42]

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Cites

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Research works printed but not linked: 49

  1. Pakzad K, Boucher BA, Kreiger N, et al. The use of herbal and other non-vitamin, non-mineral supplements among pre-and post-menopausal women in Ontario. Can J Public Health 2007;98: 383-8.
  2. Wold RS, Lopez ST, Yau CL, et al. Increasing trends in elderly persons' use of nonvitamin, nonmineral dietary supplements and concurrent use of medications. J Am Diet Assoc 2005;105: 54-63.
  3. Knudtson MD, Klein R, Lee KE, et al. A longitudinal study of nonvitamin, nonmineral supplement use: prevalence, associations, and survival in an aging population. Ann Epidemiol 2007;17:933-9.
  4. Bent S. Herbal medicine in the United States: review of efficacy, safety, and regulation. J Gen Intern Med 2008;23:854-9.
  5. Brasky TM, Lampe JW, Potter JD, et al. Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) cohort. Cancer Epidemiol Biomarkers Prev 2010;19:1696-708.
  6. Obi N, Chang-Claude J, Berger J, et al. The use of herbal preparations to alleviate climacteric disorders and risk of postmenopausal breast cancer in a German case-control study. Cancer Epidemiol Biomarkers Prev 2009;18:2207-13.
  7. Rebbeck TR, Troxel AB, Norman S, et al. A retrospective case-control study of the use of hormone-related supplements and association with breast cancer. Int J Cancer 2007;120:1523-8.
  8. Cassidy A. Dietary phyto-oestrogens: molecular mechanisms, bioavailability and importance to menopausal health. Nutr Res Rev 2005;18:183-201.
  9. Wu AH, Yu MC, Tseng CC, et al. Epidemiology of soy exposures and breast cancer risk. Br J Cancer 2008;98:9-14.
  10. Thompson LU, Boucher BA, Liu Z, et al. Phytoestrogen content of foods consumed in Canada, including isoflavones, lignans, and coumestan. Nutr Cancer 2006;54:184-201.
  11. Thompson LU, Boucher BA, Cotterchio M, et al. Dietary phytoestrogens, including isoflavones, lignans, and coumestrol, in nonvitamin, nonmineral supplements commonly consumed by women in Canada. Nutr Cancer 2007;59:176-84.
  12. Setchell KDR, Brown NM, Desai P, et al. Bioavailability of pure isoflavones in healthy humans and analysis of commercial soy isoflavone supplements. J Nutr 2001;131: 1362S-75S.
  13. Clarke DB, Bailey V, Lloyd AS. Determination of phytoestrogens in dietary supplements by LC-MS/MS. Food Addit Contam 2008;25: 534-47.
  14. Linseisen J, Piller R, Hermann S, et al. Dietary phytoestrogen intake and premenopausal breast cancer risk in a German case-control study. Int J Cancer 2004;110:284-90.
  15. Wu AH, Koh WP, Wang R, et al. Soy intake and breast cancer risk in Singapore Chinese Health Study. Br J Cancer 2008;99:196-200.
  16. Cotterchio M, Boucher BA, Kreiger N, et al. Dietary phytoestrogen intake-lignans and isoflavones-and breast cancer risk (Canada). Cancer Causes Control 2008;19:259-72.
  17. Trock BJ, Hilakivi-Clarke L, Clarke R. Meta- analysis of soy intake and breast cancer risk. J Natl Cancer Inst 2006;98:459-71.
  18. Dong JY, Qin LQ. Soy isoflavones consumption and risk of breast cancer incidence or recurrence: a meta-analysis of prospective studies. Breast Cancer Res Treat 2011;125:315-23.
  19. Horn-Ross PL, Hoggatt KJ, West DW, et al. Recent diet and breast cancer risk: the California Teachers Study (USA). Cancer Causes Control 2002;13:407-15.
  20. Touillaud MS, Thiebaut ACM, Niravong M, et al. No association between dietary phytoestrogens and risk of premenopausal breast cancer in a French cohort study. Cancer Epidemiol Biomarkers Prev 2006;15:2574-6.
  21. Cho YA, Kim J, Park KS, et al. Effect of dietary soy intake on breast cancer risk according to menopause and hormone receptor status. Eur J Clin Nutr 2010;64:924-32.
  22. Dai Q, Shu XO, Jin F, et al. Population-based case-control study of soyfood intake and breast cancer risk in Shanghai. Br J Cancer 2001;85: 372-8.
  23. Thanos J, Cotterchio M, Boucher BA, et al. Adolescent dietary phytoestrogen intake and breast cancer risk (Canada). Cancer Causes Control 2006;17:1253-61.
  24. Anderson LN, Cotterchio M, Boucher BA. Lecithin supplements and breast cancer risk. Epidemiology 2011;22:444-6.
  25. He X, Liu RH. Cranberry phytochemicals: isolation, structure elucidation, and their antiproliferative and antioxidant activities. J Agric Food Chem 2006;54:7069-74.
  26. Manthey JA, Guthrie N. Antiproliferative activities of citrus flavonoids against six human cancer cell lines. J Agric Food Chem 2002;50:5837-43.
  27. Hu K, Yao X. The cytotoxicity of methyl protoneogracillin (NSC-698793) and gracillin (NSC-698787), two steroidal saponins from the rhizomes of dioscorea collettii var. hypoglauca, against human cancer cells in vitro. Phytother Res 2003;17:620-6.
  28. Pellegrina CD, Padovani G, Mainente F, et al. Antitumor potential of a gallic acid-containing phenolic fraction from Oenothera biennis. Cancer Lett 2005;226:17-25.
  29. Boucher BA, Thompson LU, Kreiger N, et al. Hormone-related supplements and breast cancer risk: need for improved measurement of supplement use. Int J Cancer 2008;123:2465-6.
  30. Messina M, Nagata C, Wu AH. Estimated Asian adult soy protein and isoflavone intakes. Nutr Cancer 2006;55:1-12.
  31. Messina M, Wu AH. Perspectives on the soy- breast cancer relation. Am J Clin Nutr 2009;89: 1673S-9S.
  32. V C 2012 UICC 10970215, 2013, 6, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/ijc.27769, Wiley Online Library on [12/08/2023]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License in Asian-Americans. Carcinogenesis 2002;23: 1491-6.
  33. Shu XO, Jin F, Dai Q, et al. Soyfood intake during adolescence and subsequent risk of breast cancer among Chinese women. Cancer Epidemiol Biomarkers Prev 2001;10:483-8.
  34. Boucher BA, Cotterchio M, Kreiger N, et al. Soy formula and breast cancer risk. Epidemiology 2008;19:165-6.
  35. Patterson RE, Kristal AR, Levy L, et al. Validity of methods used to assess vitamin and mineral supplement use. Am J Epidemiol 1998;148:643-9.
  36. Setchell KDR, Brown NM, Zhao X, et al. Soy isoflavone phase II metabolism differs between rodents and humans: implications for the effect on breast cancer risk. Am J Clin Nutr 2011;94: 1284-94.
  37. Klein MA, Nahin RL, Messina MJ, et al. Guidance from an NIH workshop in designing, implementing, and reporting clinical studies of soy interventions. J Nutr 2010;140: 1192S-204S.
  38. Cassidy A, Albertazzi P, Nielsen IL, et al. Critical review of health effects of soybean phyto- oestrogens in post-menopausal women. Proc Nutr Soc 2006;65:76-92.
  39. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 1998;90: 1371-88.
  40. Hwang CS, Kwak HS, Lim HJ, et al. Isoflavone metabolites and their in vivo dual functions: they can act as an estrogenic agonist or antagonist depending on the estrogen concentration. J Steroid Biochem Mol Biol 2006;101:246-53.
  41. Hooper L, Ryder JJ, Kurzer MS, et al. Effects of soy protein and isoflavones on circulating hormone concentrations in pre-and post- menopausal women: a systematic review and meta-analysis. Hum Reprod Update 2009;15: 423-40.
  42. Cassidy A, Brown JE, Hawdon A, et al. Factors affecting the bioavailability of soy isoflavones in humans after ingestion of physiologically relevant levels from different soy foods. J Nutr 2006;136: 45-51.
  43. Hedlund TE, Maroni PD, Ferucci PG, et al. Long-term dietary habits affect soy isoflavone metabolism and accumulation in prostatic fluid in Caucasian men. J Nutr 2005;135:1400-6.
  44. Setchell KDR, Zhao X, Shoaf SE, et al. The pharmacokinetics of S-(-)equol administered as SE5-OH tablets to healthy postmenopausal women. J Nutr 2009;139:2037-43.
  45. Li K, Kaaks R, Linseisen J, et al. Consistency of vitamin and/or mineral supplement use and demographic, lifestyle and health-status predictors: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort. Br J Nutr 2010;104:1058-64.
  46. Boucher BA, Cotterchio M, Curca IA, et al. Intake of phytoestrogen foods and supplements among women recently diagnosed with breast cancer in Ontario, Canada. Nutr Cancer 2012;64: 695-703.
  47. Dwyer JT, Picciano MF, Betz JM, et al. Progress in developing analytical and label-based dietary supplement databases at the NIH Office of Dietary Supplements. J Food Compost Anal 2008; 21:S83-93.
  48. Boucher BA. Dietary supplements, quality scores and missing data in the review of validation studies. Br J Nutr 2010;104:1878-9.
  49. Boucher B, Cotterchio M, Kreiger N, et al. Validity and reliability of the Block98 food- frequency questionnaire in a sample of Canadian women. Public Health Nutr 2006;9: 84-93. Epidemiology 1450 Isoflavone supplements and breast cancer risk Int. J. Cancer: 132, 1439-1450 (2013)

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Authors
Boucher, B. A., Cotterchio, M., Anderson, L. N., Kreiger, N., Kirsh, V. A., & Thompson, L. U.
Affiliations
  • University of Toronto (CA)
  • Cancer Care Ontario (CA)
Corresponding author
Boucher, Beatrice A.
ORCID
Venue
International Journal of Cancer
Publisher
Wiley
Published
2012-09-18
Volume
132
Issue
6
Pages
1439-1450
ISSN
  • 0020-7136 (ISSN-L)
  • 1097-0215
DOI
10.1002/ijc.27769
OpenAlex
W1983880172
Cited by
40
References
1
Citations by year
2025: 2 · 2024: 1 · 2023: 1 · 2021: 5 · 2019: 2 · 2018: 5 · 2017: 4 · 2016: 6 · 2015: 6 · 2014: 3 · 2013: 5
FWCI
3.22
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • International Journal of Cancer (publishedVersion)
  • PubMed (publishedVersion)
Funders
Canadian Breast Cancer Research Alliance (13572)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Phytoestrogen effects and research
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
  • Health Sciences › Medicine › Oncology › Cancer Risks and Factors
Keywords
postmenopausal breast cancer, breast cancer risk reduction, herbal supplements, phytoestrogens, dietary isoflavones, Ontario Cancer Registry, Ontario, case-control study, hormone replacement therapy alternatives
MeSH terms
Adult, Aged, Breast Neoplasms, Female, Humans, Isoflavones, Middle Aged, Receptors, Estrogen, Receptors, Progesterone, Risk, Logistic Models, Postmenopause, Dietary Supplements

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