Breast Cancer Research and Treatment

, Volume 125, Issue 2, pp 519–527 | Cite as

Vegetable intake is associated with reduced breast cancer recurrence in tamoxifen users: a secondary analysis from the Women’s Healthy Eating and Living Study

  • Cynthia A. Thomson
  • Cheryl L. Rock
  • Patricia A. Thompson
  • Bette J. Caan
  • Ellen Cussler
  • Shirley W. Flatt
  • John P. Pierce
Epidemiology

Abstract

The protective effect of vegetables on the risk of breast cancer recurrence is uncertain. We sought to evaluate the association between breast cancer recurrence and vegetable intake including analyses stratified on tamoxifen use. Experimental evidence of anti-carcinogenic activity of phytochemicals in cruciferous vegetables in combination with tamoxifen led to specific evaluation of this class of vegetables as well. To assess the association between vegetable intake and breast cancer recurrence, vegetable intake from repeat 24-h dietary recalls were examined as a secondary analysis of 3,080 breast cancer survivors enrolled in the Women’s Healthy Eating and Living (WHEL) Study. At the time of enrollment women were, on average, 23.5 months post-diagnosis. The hazard of recurrence, controlling for relevant and significant clinical and demographic variables, with vegetable intake was assessed overall and separately for women taking tamoxifen. WHEL participants reported mean baseline intakes (\({\bar{\text {x}}}\), SE) of 3.1 ± 0.05 and 0.5 ± 0.02 servings/day of total and cruciferous vegetables, respectively. Baseline vegetable intake in the highest as compared to lowest tertiles was associated with an overall lower adjusted hazard ratios (HR) for recurrence of 0.69, 95% CI 0.55–0.87. Among women taking tamoxifen, the HRs were 0.56, 95% CI 0.41–0.77 for total vegetables and 0.65, 95% CI 0.47–0.89 for cruciferous vegetable intake. The hazard in women using tamoxifen who reported cruciferous vegetable intake above the median and who were within the highest tertile of total vegetable intake was HR 0.48; 95% CI 0.32–0.70. This secondary analysis in over 3,000 breast cancer survivors suggests that baseline vegetable intake may be associated with a reduction in the risk of breast cancer recurrent or new events particularly for those using tamoxifen. Such associations should be explored further as the possibility that vegetable intake is simply a surrogate for other health-promoting behaviors cannot be ruled out.

Keywords

Diet Breast cancer Vegetables Tamoxifen 

Abbreviations

WHEL

Women’s Healthy Eating and Living

BMI

Body mass index

HR

Hazards ratio

CI

Confidence interval

SERM

Select estrogen receptor modulator

US

United States

USDA

United States Department of Agriculture

NDS

Nutrient database software

References

  1. 1.
    American Cancer Society. Breast Cancer Facts and Figures 2007–2008. Atlanta: American Cancer Society, Inc. http://www.cancer.org/downloads/STT/BCFF-Final.pdf
  2. 2.
    Bessaoud F, Daures JP, Gerber M (2008) Dietary factors and breast cancer risk: a case control study among a population in Southern France. Nutr Cancer 60(2):177–187CrossRefPubMedGoogle Scholar
  3. 3.
    Zhang CX, Ho SC, Chen YM, Fu JH, Cheng SZ, Lin FY (2009) Greater vegetable and fruit intake is associated with a lower risk of breast cancer among Chinese women. Int J Cancer 125(1):181–188CrossRefPubMedGoogle Scholar
  4. 4.
    Edefonti V, Randi G, Decardi A, La Vecchia C, Boseti C, Francheschi S, Dal Maso L, Ferraroni M (2009) Clustering of dietary habits and the risk of breast and ovarian cancers. Ann Oncol 20(3):581–590CrossRefPubMedGoogle Scholar
  5. 5.
    Wang C, Baumgartner RN, Yang D, Slattery ML, Murtaugh MA, Byers T, Hines LM, Giuliano AR, Baumgartner KB (2008) No evidence of association between breast cancer risk and dietary carotenoids, retinols, vitamin C and tocopherols in Southwestern Hispanic and non-Hispanic women. Breast Cancer Res Treat 114(1):137–145CrossRefPubMedGoogle Scholar
  6. 6.
    Smith-Warner SA, Spiegelman D, Yaun SS, Adami HO, Beeson L, 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 (2001) Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies. JAMA 285(6):769–776CrossRefPubMedGoogle Scholar
  7. 7.
    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 CA, Wasserman L, Natarajan L, Thomas RG, Gilpin EA, Women’s Healthy Eating Living (WHEL) Study Group (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):728–756CrossRefPubMedGoogle Scholar
  8. 8.
    Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, Rock CL, Kealey S, Al-Delaimy WK, Bardwell WA, Carlson R, Emond JA, Faerber S, Gold EB, Hajek RA, Hollenbach K, Jones LA, Karanja N, Madlensky L, Marshall J, Newman VA, Ritenbaugh C, Thomson CA, Wasserman L, Stefanick ML (2007) The influence of a very high vegetable-fruit-fiber, low-fat diet on prognosis following treatment for breast cancer: the Women’s Healthy Eating and Living (WHEL) randomized trial. JAMA 298:289–298CrossRefPubMedGoogle Scholar
  9. 9.
    Pierce JP, Stefanick ML, Flatt SW, Natarajan L, Sternfeld B, Madlensky L, Al-Delaimy W, Thomson CA, Kealey S, Hajek R, Parker BA, Newman VA, Caan B, Rock CL, For the WHEL Study Group (2007) Greater survival in physically active women with high vegetable-fruit intake regardless of obesity in breast cancer cohort. J Clin Oncol 25:2345–2351CrossRefPubMedGoogle Scholar
  10. 10.
    Hirsch K, Atzmon A, Danilenko M, Levy J, Sharoni Y (2007) Lycopene and other carotenoids inhibit estrogenic activity of 17-estradiol and genistein in cancer cells. Breast Cancer Res Treat 104:221–230CrossRefPubMedGoogle Scholar
  11. 11.
    Prakash P, Russell RM, Krinsky NI (2001) In vitro inhibition of proliferation of estrogen-dependent and estrogen-independent human breast cancer cells treated with carotenoids or retinoids. J Nutr 131(5):2574–2580Google Scholar
  12. 12.
    Cover CM, Hsieh SJ, Cram EJ, Hong C, Riby JE, Bjeldanes LF, Firestone GL (1999) Indole-3-carbinol and tamoxifen cooperate to arrest the cell cycle of MCF-7 human breast cancer cells. Cancer Res 59(6):1244–1251PubMedGoogle Scholar
  13. 13.
    Nho W, Jeffrey E (2001) The synergistic upregulation of phase II detoxification enzymes by glucosinolate breakdown products in cruciferous vegetables. Toxicol Appl Pharmacol 174(2):146–152CrossRefPubMedGoogle Scholar
  14. 14.
    Wu HT, Lin SH, Chen YH (2005) Inhibition of cell proliferation and in vitro markers of angiogenesis by indole-3-carbinol a major indole metabolite present in cruciferous vegetables. J Agric Food Chem 53(13):5164–5169CrossRefPubMedGoogle Scholar
  15. 15.
    Fowke JH, Morrow JD, Motley S, Bostick RM, Ness RM (2006) Brassica vegetable consumption reduces urinary F2-isoprostane levels independent of micronutrient intake. Carcinogenesis 27:2096–2102CrossRefPubMedGoogle Scholar
  16. 16.
    Verhagen H, Poulsen HE, Loft S, van Poppel G, Willems MI, van Bladeren PJ (1995) Reduction of oxidative DNA-damage in humans by brussels sprouts. Carcinogenesis 16:969–970CrossRefPubMedGoogle Scholar
  17. 17.
    Fisher B, Costantino JP, Wickerman DL, Cecchini RS, Cronin WM, Robidoux A, Bevers TB, Kavanah MT, Atkins JN, Margolese RG, Runowicz CD, James JM, Ford LG, Wolmark N (2005) Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast Cancer and Bowel Project P-1 Study. J Natl Cancer Inst 97(22):1652–1662CrossRefPubMedGoogle Scholar
  18. 18.
    Malejka-Giganti D, Parkin DR, Bennett KK, Lu Y, Decker RW, Niehans GA, Bliss RL (2007) Suppression of mammary gland carcinogenesis by post-initiation treatment of rats with tamoxifen or indole-3-carbinol or their combination. Eur J Cancer Prev 16:130–141CrossRefPubMedGoogle Scholar
  19. 19.
    Wang TT, Milner MJ, Milner JA, Kim YS (2006) Estrogen receptor alpha as a target for indole-3-carbinol. J Nutr Biochem 17:659–664CrossRefPubMedGoogle Scholar
  20. 20.
    Ramirez MC, Singletary K (2009) Regulation of estrogen receptor alpha expression in human breast cancer cells by sulforaphane. J Nutr Biochem 20(3):195–201CrossRefPubMedGoogle Scholar
  21. 21.
    Conway JM, Ingwersen LA, Vinyard BT, Moshfegh AJ (2003) Effectiveness of the U.S. Department of Agriculture 5-step multi-pass method in assessing food intake in obese and nonobese women. Am J Clin Nutr 77(5):1171–1178PubMedGoogle Scholar
  22. 22.
    US Department of Agriculture, Agricultural Research Service (2007) USDA National Nutrient Database for Standard Reference, Release 20. Nutrient Data Laboratory Home Page. http://www.ars.usda.gov/ba/bhnrc/ndl
  23. 23.
    Women’s Health Initiative (2010) WHI Personal Habits Questionnaire. http://www.whiscience.org/data/forms/F34v2.pdf
  24. 24.
    Johnson-Kozlow M, Rock CL, Gilpin EA, Hollenbach KA, Pierce JP (2007) Validation of the WHI brief physical activity questionnaire among women diagnosed with breast cancer. Am J Health Behav 31(2):193–202PubMedGoogle Scholar
  25. 25.
    Rock CL, Natarajan L, Pu M, Thomson CA, Flatt SW, Caan BJ, Gold EB, Al-Delaimy WK, Newman VA, Hajek RA, Stefanick ML, Pierce JP (2009) Longitudinal biological exposure to carotenoids is associated with breast cancer-free survival in the Women’s Healthy Eating and Living study. Cancer Epidemiol Biomarkers Prev 18:486–494CrossRefPubMedGoogle Scholar
  26. 26.
    Rock CL, Flatt SW, Natarajan L, Thomson CA, Bardwell WA, Newman VA, Hollenbach KA, Jones L, Caan BJ, Pierce JP (2005) Plasma carotenoids and recurrence-free survival in women with a history of breast cancer. J Clin Oncol 23:6631–6638CrossRefPubMedGoogle Scholar
  27. 27.
    Thomson CA, Flatt SW, Rock CL, Ritenbaugh C, Newman VA, Pierce JP (2002) Increased fruit, vegetable and fiber intake and lower fat intake reported among women previously treated for invasive breast cancer. J Am Diet Assoc 102(6):801–808CrossRefPubMedGoogle Scholar
  28. 28.
    McCann SE, Thompson LU, Nie J, Dorn J, Trevison M, Shields PG, Ambrosone CB, Edge SB, Li HF, Kasprzak C, Freudenheim JL (2010) Dietary lignin intake in relation to survival among women with breast cancer: the Western New York exposures and breast cancer (WEB) study. Breast Cancer Res Treat 122(1):229–235CrossRefPubMedGoogle Scholar
  29. 29.
    Katchamart S, Stresser DM, Dehal SS, Kupfer D, Williams DE (2000) Concurrent flavin-containing monooxygenase down-regulation and cytochrome p450 induction by dietary indoles in rat: Implications for drug-drug interactions. Drug Metab Dispos 28(8):930–936PubMedGoogle Scholar
  30. 30.
    Rock CL, Flatt SW, Laughlin GA, Gold EB, Thomson CA, Natarajan L, Jones LA, Caan BJ, Stefanick ML, Hajek RA, Al-Delaimy WK, Stanczyk FZ, Pierce JP, For The Women’s Healthy Eating and Living Study Group (2008) Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer. Cancer Epidemiol Biomarkers Prev 17:614–620CrossRefPubMedGoogle Scholar
  31. 31.
    Gold EB, Pierce JP, Nataranjan L, Stefanick ML, Laughlin GA, Caan BJ, Flatt SW, Emond JA, Saquib N, Madlensky L, Kealey S, Wasserman L, Thomson CA, Rock CL, Parker BA, Karanja M, Jones L, Hajek R, Pu M, Mortimer JE (2008) Dietary pattern influences breast cancer prognosis in women without hot flashes: The Women’s Healthy Eating and Living Trial. J Clin Oncol 27(3):352–359CrossRefPubMedGoogle Scholar
  32. 32.
    Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF (2004) Pilot study: effects of 3,3′-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with history of early stage breast cancer. Nutr Cancer 50(4):161–167CrossRefPubMedGoogle Scholar
  33. 33.
    Johnston CS, Taylor CA, Hampl JS (2000) More Americans eating “5-a-day”, but intake of dark green and cruciferous vegetables remain low. J Nutr 130(12):3063–3067PubMedGoogle Scholar
  34. 34.
    Natarjan L, Flatt SW, Sun X, Gamst AC, Major JM, Rock CL, Al-Delaimy W, Thomson CA, Newman VA, Pierce JP (2006) Validity and systematic error in measuring carotenoid consumption with dietary self-report instruments. Am J Epidemiol 163(8):770–778CrossRefGoogle Scholar
  35. 35.
    Kellen E, Vansant G, Christiaens MR, Neven P, Van Limbergen E (2009) Lifestyle changes and breast cancer prognosis. Breast Cancer Res Treat 114:13–22CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2010

Authors and Affiliations

  • Cynthia A. Thomson
    • 1
  • Cheryl L. Rock
    • 2
  • Patricia A. Thompson
    • 3
  • Bette J. Caan
    • 4
  • Ellen Cussler
    • 5
  • Shirley W. Flatt
    • 2
  • John P. Pierce
    • 2
  1. 1.Department of Nutritional ScienceUniversity of Arizona Cancer Center, University of ArizonaTucsonUSA
  2. 2.Moores UCSD Cancer CenterUniversity of CaliforniaSan Diego, La JollaUSA
  3. 3.University of Arizona Cancer Center, University of ArizonaTucsonUSA
  4. 4.Kaiser Permanente Northern CaliforniaOaklandUSA
  5. 5.Department of PhysiologyUniversity of ArizonaTucsonUSA

Personalised recommendations