Skip to main content

Advertisement

Log in

Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Soy isoflavones, structurally similar to endogenous estrogens, may affect breast cancer through both hormonally mediated and non-hormonally related mechanisms. Although the effects of soy are not well understood, some breast cancer survivors increase their soy intake post-diagnosis in attempt to improve their prognosis. Therefore, we examined the role of soy isoflavone intake and the risk of breast cancer recurrence by hormone receptor status, menopausal status, and tamoxifen therapy. A cohort of 1,954 female breast cancer survivors, diagnosed during 1997–2000, was prospectively followed for 6.31 years and 282 breast cancer recurrences were ascertained. Isoflavone intake was assessed by mailing modified Block and supplemental soy food frequency questionnaires to participants, on average 23 months post-diagnosis. Risk of breast cancer recurrence, measured by hazard ratios (HR) and 95% confidence intervals (CI), was estimated using multivariable delayed entry Cox proportional hazards models. Suggestive trends for a reduced risk of cancer recurrence were observed with increasing quintiles of daidzein and glycetin intake compared to no intake among postmenopausal women (P for trend: P = 0.08 for daidzein, P = 0.06 for glycetin) and among tamoxifen users (P = 0.10 for daidzein, P = 0.05 for glycetin). Among postmenopausal women treated with tamoxifen, there was an approximately 60% reduction in breast cancer recurrence comparing the highest to the lowest daidzein intakes (>1,453 vs. <7.7 μg/day; HR, 0.48; 95% CI, 0.21–0.79, = 0.008). Soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in women receiving tamoxifen therapy and moreover, appears not to interfere with tamoxifen efficacy. Further confirmation is required in other large prospective studies before recommendations regarding soy intake can be issued to breast cancer survivors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Reinli K, Block G (1996) Phytoestrogen content of foods–a compendium of literature values. Nutr Cancer 26(2):123–148

    Article  CAS  PubMed  Google Scholar 

  2. Murphy PA, Song T, Buseman G, Barua K, Beecher GR, Trainer D, Holden J (1999) Isoflavones in retail and institutional soy foods. J Agric Food Chem 47(7):2697–2704. doi:10.1021/jf981144o

    Article  CAS  PubMed  Google Scholar 

  3. Curado MP, Edwards B, Shin HR, Storm H, Ferlay J, Heanue M, Boyle P (eds) (2007) Cancer incidence in five continents No. 160. IARC Scientific Publications, Lyon

    Google Scholar 

  4. Parkin DM (1989) Cancers of the breast, endometrium and ovary: geographic correlations. Eur J Cancer Clin Oncol 25(12):1917–1925. doi:10.1016/0277-5379(89)90373-8

    Article  CAS  PubMed  Google Scholar 

  5. Rose DP, Boyar AP, Wynder EL (1986) International comparisons of mortality rates for cancer of the breast, ovary, prostate, and colon, and per capita food consumption. Cancer 58(11):2363–2371. doi:10.1002/1097-0142(19861201)58:11<2363::AID-CNCR2820581102>3.0.CO;2-#

    Article  CAS  PubMed  Google Scholar 

  6. Kaur JS (2000) Migration patterns and breast carcinoma. Cancer 88(5 Suppl):1203–1206. doi:10.1002/(SICI)1097-0142(20000301)88:5+<1203::AID-CNCR4>3.0.CO;2-#

    Article  CAS  PubMed  Google Scholar 

  7. Stanford JL, Herrinton LJ, Schwartz SM, Weiss NS (1995) Breast cancer incidence in Asian migrants to the United States and their descendants. Epidemiology 6(2):181–183. doi:10.1097/00001648-199503000-00017

    Article  CAS  PubMed  Google Scholar 

  8. Trichopoulos D, Yen S, Brown J, Cole P, MacMahon B (1984) The effect of westernization on urine estrogens, frequency of ovulation, and breast cancer risk. A study of ethnic Chinese women in the Orient and the USA. Cancer 53(1):187–192. doi:10.1002/1097-0142(19840101)53:1<187::AID-CNCR2820530133>3.0.CO;2-N

    Article  CAS  PubMed  Google Scholar 

  9. Ziegler RG, Hoover RN, Pike MC, Hildesheim A, Nomura AM, West DW, Wu-Williams AH, Kolonel LN, Horn-Ross PL, Rosenthal JF, Hyer MB (1993) Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst 85(22):1819–1827. doi:10.1093/jnci/85.22.1819

    Article  CAS  PubMed  Google Scholar 

  10. Adlercreutz H (1998) Epidemiology of phytoestrogens. Baillieres Clin Endocrinol Metab 12(4):605–623. doi:10.1016/S0950-351X(98)80007-4

    Article  CAS  PubMed  Google Scholar 

  11. Kato I, Tominaga S, Kuroishi T (1987) Relationship between westernization of dietary habits and mortality from breast and ovarian cancers in Japan. Jpn J Cancer Res 78(4):349–357

    CAS  PubMed  Google Scholar 

  12. Parkin DM, Khlat M (1996) Studies of cancer in migrants: rationale and methodology. Eur J Cancer 32A(5):761–771. doi:10.1016/0959-8049(96)00062-7

    Article  CAS  PubMed  Google Scholar 

  13. Trock BJ, Hilakivi-Clarke L, Clarke R (2006) Meta-analysis of soy intake and breast cancer risk. J Natl Cancer Inst 98(7):459–471

    CAS  PubMed  Google Scholar 

  14. Santell RC, Chang YC, Nair MG, Helferich WG (1997) Dietary genistein exerts estrogenic effects upon the uterus, mammary gland and the hypothalamic/pituitary axis in rats. J Nutr 127(2):263–269

    CAS  PubMed  Google Scholar 

  15. Wang TT, Sathyamoorthy N, Phang JM (1996) Molecular effects of genistein on estrogen receptor mediated pathways. Carcinogenesis 17(2):271–275. doi:10.1093/carcin/17.2.271

    Article  PubMed  Google Scholar 

  16. Phytoestrogens (2005) In: Faith Yildiz (ed) Functional foods. CRC Press, Boca Raton

  17. Magee PJ, Rowland IR (2004) Phyto-oestrogens, their mechanism of action: current evidence for a role in breast and prostate cancer. Br J Nutr 91(4):513–531. doi:10.1079/BJN20031075

    Article  CAS  PubMed  Google Scholar 

  18. Moon YJ, Wang X, Morris ME (2006) Dietary flavonoids: effects on xenobiotic and carcinogen metabolism. Toxicol In Vitro 20(2):187–210. doi:10.1016/j.tiv.2005.06.048

    Article  CAS  PubMed  Google Scholar 

  19. Constantinou AI, White BE, Tonetti D, Yang Y, Liang W, Li W, van Breemen RB (2005) The soy isoflavone daidzein improves the capacity of tamoxifen to prevent mammary tumours. Eur J Cancer 41(4):647–654. doi:10.1016/j.ejca.2004.12.005

    Article  CAS  PubMed  Google Scholar 

  20. Harris PF, Remington PL, Trentham-Dietz A, Allen CI, Newcomb PA (2002) Prevalence and treatment of menopausal symptoms among breast cancer survivors. J Pain Symptom Manage 23(6):501–509. doi:10.1016/S0885-3924(02)00395-0

    Article  PubMed  Google Scholar 

  21. Morris KT, Johnson N, Homer L, Walts D (2000) A comparison of complementary therapy use between breast cancer patients and patients with other primary tumor sites. Am J Surg 179(5):407–411. doi:10.1016/S0002-9610(00)00358-5

    Article  CAS  PubMed  Google Scholar 

  22. Messina M, McCaskill-Stevens W, Lampe JW (2006) Addressing the soy and breast cancer relationship: review, commentary, and workshop proceedings. J Natl Cancer Inst 20;98(18):1275–1284

    Google Scholar 

  23. Jones JL, Daley BJ, Enderson BL, Zhou JR, Karlstad MD (2002) Genistein inhibits tamoxifen effects on cell proliferation and cell cycle arrest in T47D breast cancer cells. Am Surg 68(6):575–577

    PubMed  Google Scholar 

  24. Lee MM, Lin SS, Wrensch MR, Adler SR, Eisenberg D (2000) Alternative therapies used by women with breast cancer in four ethnic populations. J Natl Cancer Inst 92(1):42–47. doi:10.1093/jnci/92.1.42

    Article  CAS  PubMed  Google Scholar 

  25. Pinto BM, Maruyama NC, Clark MM, Cruess DG, Park E, Roberts M (2002) Motivation to modify lifestyle risk behaviors in women treated for breast cancer. Mayo Clin Proc 77(2):122–129

    Article  PubMed  Google Scholar 

  26. Salminen E, Heikkila S, Poussa T, Lagstrom H, Saario R, Salminen S (2002) Female patients tend to alter their diet following the diagnosis of rheumatoid arthritis and breast cancer. Prev Med 34(5):529–535. doi:10.1006/pmed.2002.1015

    Article  PubMed  Google Scholar 

  27. Caan B, Sternfeld B, Gunderson E, Coates A, Quesenberry C, Slattery ML (2005) Life after cancer epidemiology (LACE) study: a cohort of early stage breast cancer survivors (United States). Cancer Causes Control 16(5):545–556. doi:10.1007/s10552-004-8340-3

    Article  PubMed  Google Scholar 

  28. Pierce JP, Faerber S, Wright FA, Rock CL, Newman V, Flatt SW, Kealey S, Jones VE, Caan BJ, Gold EB, Haan M, Hollenbach KA, Jones L, Marshall JR, Ritenbaugh C, Stefanick ML, Thomson C, Wasserman L, Natarajan L, Thomas RG, Gilpin EA (2002) A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the women’s healthy eating and living (WHEL) study. Control Clin Trials 23(6):728–756. doi:10.1016/S0197-2456(02)00241-6

    Article  PubMed  Google Scholar 

  29. Block G, Hartman AM, Dresser CM, Carroll MD, Gannon J, Gardner L (1986) A data-based approach to diet questionnaire design and testing. Am J Epidemiol 124(3):453–469

    CAS  PubMed  Google Scholar 

  30. Kirk P, Patterson RE, Lampe J (1999) Development of a soy food frequency questionnaire to estimate isoflavone consumption in US adults. J Am Diet Assoc 99(5):558–563. doi:10.1016/S0002-8223(99)00139-X

    Article  CAS  PubMed  Google Scholar 

  31. Frankenfeld CL, Patterson RE, Horner NK, Neuhouser ML, Skor HE, Kalhorn TF, Howald WN, Lampe JW (2003) Validation of a soy food-frequency questionnaire and evaluation of correlates of plasma isoflavone concentrations in postmenopausal women. Am J Clin Nutr 77(3):674–680

    CAS  PubMed  Google Scholar 

  32. Pillow PC, Duphorne CM, Chang S, Contois JH, Strom SS, Spitz MR, Hursting SD (1999) Development of a database for assessing dietary phytoestrogen intake. Nutr Cancer 33(1):3–19

    Article  CAS  PubMed  Google Scholar 

  33. Newman V, Rock CL, Faerber S, Flatt SW, Wright FA, Pierce JP (1998) Dietary supplement use by women at risk for breast cancer recurrence. The women’s healthy eating and living study group. J Am Diet Assoc 98(3):285–292. doi:10.1016/S0002-8223(98)00068-6

    Article  CAS  PubMed  Google Scholar 

  34. Jewell NP (2003) Statistics for epidemiology, 1st edn. Chapman & Hall/CRC Press, Boca Raton

    Google Scholar 

  35. Arai Y, Watanabe S, Kimira M, Shimoi K, Mochizuki R, Kinae N (2000) Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J Nutr 130(9):2243–2250

    CAS  PubMed  Google Scholar 

  36. Wakai K, Egami I, Kato K, Kawamura T, Tamakoshi A, Lin Y, Nakayama T, Wada M, Ohno Y (1999) Dietary intake and sources of isoflavones among Japanese. Nutr Cancer 33(2):139–145. doi:10.1207/S15327914NC330204

    Article  CAS  PubMed  Google Scholar 

  37. Yamamoto S, Sobue T, Sasaki S, Kobayashi M, Arai Y, Uehara M, Adlercreutz H, Watanabe S, Takahashi T, Iitoi Y, Iwase Y, Akabane M, Tsugane S (2001) Validity and reproducibility of a self-administered food-frequency questionnaire to assess isoflavone intake in a japanese population in comparison with dietary records and blood and urine isoflavones. J Nutr 131(10):2741–2747

    CAS  PubMed  Google Scholar 

  38. Boyapati SM, Shu XO, Ruan ZX, Dai Q, Cai Q, Gao YT, 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. doi:10.1007/s10549-004-6019-9

    Article  PubMed  Google Scholar 

  39. Carey LA, Perou CM, Livasy CA, Dressler LG, Cowan D, Conway K, Karaca G, Troester MA, Tse CK, Edmiston S, Deming SL, Geradts J, Cheang MC, Nielsen TO, Moorman PG, Earp HS, Millikan RC (2006) Race, breast cancer subtypes, and survival in the Carolina Breast Cancer Study. JAMA 295(21):2492–2502. doi:10.1001/jama.295.21.2492

    Article  CAS  PubMed  Google Scholar 

  40. Suzuki T, Matsuo K, Tsunoda N, Hirose K, Hiraki A, Kawase T, Yamashita T, Iwata H, Tanaka H, Tajima K (2008) Effect of soybean on breast cancer according to receptor status: a case-control study in Japan. Int J Cancer 123(7):1674–1680. doi:10.1002/ijc.23644

    Article  CAS  PubMed  Google Scholar 

  41. Wu AH, Pike MC, Williams LD, Spicer D, Tseng CC, Churchwell MI, Doerge DR (2007) Tamoxifen, soy, and lifestyle factors in Asian American women with breast cancer. J Clin Oncol 20;25(21):3024–3030

    Article  CAS  Google Scholar 

  42. Gotoh T, Yamada K, Ito A, Yin H, Kataoka T, Dohi K (1998) Chemoprevention of N-nitroso-N-methylurea-induced rat mammary cancer by miso and tamoxifen, alone and in combination. Jpn J Cancer Res 89(5):487–495

    CAS  PubMed  Google Scholar 

  43. Mai Z, Blackburn GL, Zhou JR (2007) Soy phytochemicals synergistically enhance the preventive effect of tamoxifen on the growth of estrogen-dependent human breast carcinoma in mice. Carcinogenesis 28(6):1217–1223. doi:10.1093/carcin/bgm004

    Article  CAS  PubMed  Google Scholar 

  44. Chen J, Halls SC, Alfaro JF, Zhou Z, Hu M (2004) Potential beneficial metabolic interactions between tamoxifen and isoflavones via cytochrome P450-mediated pathways in female rat liver microsomes. Pharm Res 21(11):2095–2104. doi:10.1023/B:PHAM.0000048202.92930.61

    Article  CAS  PubMed  Google Scholar 

  45. Wu AH, Koh WP, Wang R, Lee HP, Yu MC (2008) Soy intake and breast cancer risk in Singapore Chinese health study. Br J Cancer 99(1):196–200. doi:10.1038/sj.bjc.6604448

    Article  CAS  PubMed  Google Scholar 

  46. Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S (2003) Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst 95(12):906–913

    Article  CAS  PubMed  Google Scholar 

  47. Rothman KJ (1990) No adjustments are needed for multiple comparisons. Epidemiology 1(1):43–46

    CAS  PubMed  Google Scholar 

  48. Rothman KJ, Greenland S (1998) Modern epidemiology, 2nd edn. Lippincott Williams & Wilkins, Philadelphia

    Google Scholar 

  49. Savitz D (2003) Interpreting epidemiologic evidence: strategies for study design and analysis. Oxford University Press, New York

    Book  Google Scholar 

  50. Horn-Ross PL, John EM, Lee M, Stewart SL, Koo J, Sakoda LC, Shiau AC, Goldstein J, Davis P, Perez-Stable EJ (2001) Phytoestrogen consumption and breast cancer risk in a multiethnic population: the bay area breast cancer Study. Am J Epidemiol 154(5):434–441. doi:10.1093/aje/154.5.434

    Article  CAS  PubMed  Google Scholar 

  51. Huang MH, Harrison GG, Mohamed MM, Gornbein JA, Henning SM, Go VL, Greendale GA (2000) Assessing the accuracy of a food frequency questionnaire for estimating usual intake of phytoestrogens. Nutr Cancer 37(2):145–154. doi:10.1207/S15327914NC372_5

    Article  CAS  PubMed  Google Scholar 

  52. Kwan ML, Weltzien E, Kushi LH, Castillo A, Slattery ML, Caan B (2009) Dietary patterns and breast cancer recurrence and survival among women with early stage breast cancer. J Clin Oncol doi:10.1200/JCO.2008.19.4035

Download references

Acknowledgments

The LACE Study was funded by the National Cancer Institute (CA80027 and PC67000). Neela Guha was a 2007 DOR/CHR Fellow, and her research was supported, in part, by a grant from the Division of Research, Kaiser Permanente Northern California, to the Center for Health Research at the University of California, Berkeley. We thank all participants and study staff.

Funding sources

National Cancer Institute grants CA80027 and PC67000. 2007 DOR/CHR Fellowship funded by a grant from the Division of Research, Kaiser Permanente Northern California to the Center for Health Research at the University of California, Berkeley.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Neela Guha or Bette J. Caan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Guha, N., Kwan, M.L., Quesenberry, C.P. et al. Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology study. Breast Cancer Res Treat 118, 395–405 (2009). https://doi.org/10.1007/s10549-009-0321-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-009-0321-5

Keywords

Navigation