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Breast Cancer Research and Treatment

, Volume 114, Issue 1, pp 1–6 | Cite as

The Women’s Health Initiative Randomized Controlled Dietary Modification Trial: a post-mortem

  • Karin B. Michels
  • Walter C. Willett
Review

Abstract

Ecological correlations derived from national mortality data and case–control studies have suggested a positive relation between dietary fat and risk of breast cancer. However, in the many large prospective studies that have been conducted more recently, little or no association has been found between total fat intake and breast cancer incidence. The recently released results from the Women’s Health Initiative Fat Reduction Trial found no significant effect of a low-fat diet on risk of breast cancer or total cancer incidence. However, methodologic limitations of this trial, particularly low compliance with the dietary intervention, make these data difficult to interpret, and in the end this massive trial contributes little to our understanding of the role of fat intake in the risk of breast cancer. A substantial body of available evidence now suggests that the percentage of energy derived from fat intake during midlife does not appear to be an important risk factor for breast cancer and is not the primary reason for the large international differences in disease incidence. Diet has a major impact on breast cancer risk, mainly mediated through childhood growth rates and weight gain in later life. Minimizing weight gain during midlife or weight loss after menopause reduces the risk of postmenopausal breast cancer. Massive randomized trials of behavior change to prevent cancer will usually not be a good investment, as clear answers are unlikely. The best information on prevention by diet and lifestyle will generally come from long-term prospective studies combined with controlled trials of intermediate endpoints.

Keywords

Dietary fat Breast cancer 

References

  1. 1.
    Kolonel L, Hinds M, Hankin J (1980) Cancer patterns among migrant and native-born Japanese in Hawaii in relation to smoking, drinking, and dietary habits. In: Gelboin HV, MacMahon M, Matsushima T, Sugimura T, Takayama S, Takebe H (eds) Genetics and environmental factors in experimental and human cancer. Japan Scientific Societies Press, TokyoGoogle Scholar
  2. 2.
    Carroll KK, Gammal EB, Plunkett ER (1968) Dietary fat and mammary cancer. Can Med Assoc J 98:590–594PubMedGoogle Scholar
  3. 3.
    Howe GR, Hirohata T, Hislop TG, Iscovich JM, Yuan JM, Katsouyanni K, Lubin F, Marubini E, Modan B, Rohan T et al (1990) Dietary factors and risk of breast cancer: combined analysis of 12 case-control studies. J Natl Cancer Inst 82:561–569PubMedCrossRefGoogle Scholar
  4. 4.
    Albanes D (1987) Total calories, body weight, tumor incidence in mice. Cancer Res 47:1987–1992PubMedGoogle Scholar
  5. 5.
    Freedman LS, Clifford C, Messina M (1990) Analysis of dietary fat, calories, body weight, and the development of mammary tumors in rats and mice: a review. Cancer Res 50:5710–5719PubMedGoogle Scholar
  6. 6.
    Appleton BS, Landers RE (1986) Oil gavage effects on tumor incidence in the National Toxicology Program’s 2-year carcinogenesis bioassay. Adv Exp Med Biol 206:99–104PubMedGoogle Scholar
  7. 7.
    Committee on Diet and Health, Food and Nutrition Board, Institutes of Medicine National Research Council: Diet and Health, Washington, DC (1992)Google Scholar
  8. 8.
    Willett WC, Hunter DJ, Stampfer MJ, Colditz G, Manson JE, Spiegelman D, Rosner B, Hennekens CH, Speizer FE (1992) Dietary fat and fiber in relation to risk of breast cancer. An 8-year follow-up. JAMA 268:2037–2044PubMedCrossRefGoogle Scholar
  9. 9.
    Hunter DJ, Spiegelman D, Adami HO, Beeson L, van den Brandt PA, Folsom AR, Fraser GE, Goldbohm RA, Graham S, Howe GR et al (1996) Cohort studies of fat intake and the risk of breast cancer – a pooled analysis. N Engl J Med 334:356–361PubMedCrossRefGoogle Scholar
  10. 10.
    Smith-Warner SA, Spiegelman D, Adami HO, Beeson WL, van den Brandt PA, Folsom AR, Fraser GE, Freudenheim JL, Goldbohm RA, Graham S, Kushi LH, Miller AB, Rohan TE, Speizer FE, Toniolo P, Willett WC, Wolk A, Zeleniuch-Jacquotte A, Hunter DJ (2001) Types of dietary fat and breast cancer: a pooled analysis of cohort studies. Int J Cancer 92:767–774PubMedCrossRefGoogle Scholar
  11. 11.
    Prentice RL (1996) Measurement error and results from analytic epidemiology: dietary fat and breast cancer. J Natl Cancer Inst 88:1738–1747PubMedCrossRefGoogle Scholar
  12. 12.
    Kristal AR, Peters U, Potter JD (2005) Is it time to abandon the food frequency questionnaire? Cancer Epidemiol Biomarkers Prev 14:2826–2828PubMedCrossRefGoogle Scholar
  13. 13.
    Willett WC, Hu FB (2006) Not the time to abandon the food frequency questionnaire: point. Cancer Epidemiol Biomarkers Prev 15:1757–1758PubMedCrossRefGoogle Scholar
  14. 14.
    Kristal AR, Potter JD (2006) Not the time to abandon the food frequency questionnaire: counterpoint. Cancer Epidemiol Biomarkers Prev 15:1759–1760PubMedCrossRefGoogle Scholar
  15. 15.
    Bingham SA, Luben R, Welch A, Wareham N, Khaw KT, Day N (2003) Are imprecise methods obscuring a relation between fat and breast cancer? Lancet 362:212–214PubMedCrossRefGoogle Scholar
  16. 16.
    Willett W (1998) Nutritional epidemiology, 2nd edn. Oxford University Press, New YorkGoogle Scholar
  17. 17.
    Willett W, Stampfer M, Chu NF, Spiegelman D, Holmes M, Rimm E (2001) Assessment of questionnaire validity for measuring total fat intake using plasma lipid levels as criteria. Am J Epidemiol 154:1107–1112PubMedCrossRefGoogle Scholar
  18. 18.
    Hu FB, Stampfer MJ, Manson JE, Rimm E, Colditz GA, Rosner BA, Hennekens CH, Willett WC (1997) Dietary fat intake and the risk of coronary heart disease in women. N Engl J Med 337:1491–1499PubMedCrossRefGoogle Scholar
  19. 19.
    Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, Willett WC (2001) Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med 345:790–797PubMedCrossRefGoogle Scholar
  20. 20.
    Multiple risk factor intervention trial (1982) Risk factor changes and mortality results. Multiple Risk Factor Intervention Trial Research Group. JAMA 248:1465–1477CrossRefGoogle Scholar
  21. 21.
    Michels KB, Willett WC (1991) The Women’s Health Initiative: daughter of politics or science? In: DeVita VT, Hellman S, Rosenberg SA (eds) Cancer prevention. Lippincott, PhiladelphiaGoogle Scholar
  22. 22.
    Willett WC, Stampfer MJ (1990) Dietary fat and cancer: another view. Cancer Causes Control 1:103–109CrossRefGoogle Scholar
  23. 23.
    Prentice RL, Caan B, Chlebowski RT, Patterson R, Kuller LH, Ockene JK, Margolis KL, Limacher MC, Manson JE, Parker LM, Paskett E, Phillips L, Robbins J, Rossouw JE, Sarto GE, Shikany JM, Stefanick ML, Thomson CA, Van Horn L, Vitolins MZ, Wactawski-Wende J, Wallace RB, Wassertheil-Smoller S, Whitlock E, Yano K, Adams-Campbell L, Anderson GL, Assaf AR, Beresford SA, Black HR, Brunner RL, Brzyski RG, Ford L, Gass M, Hays J, Heber D, Heiss G, Hendrix SL, Hsia J, Hubbell FA, Jackson RD, Johnson KC, Kotchen JM, LaCroix AZ, Lane DS, Langer RD, Lasser NL, Henderson MM (2006) Low-fat dietary pattern and risk of invasive breast cancer: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295:629–642PubMedCrossRefGoogle Scholar
  24. 24.
    Prentice RL, Sheppard L (1990) Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption. Cancer Causes Control 1:81–97; discussion 99–109PubMedCrossRefGoogle Scholar
  25. 25.
    Prentice RL, Thomson CA, Caan B, Hubbell FA, Anderson GL, Beresford SAA, Pettinger M, Lane DS, Lessin L, Yasmeen S, Singh B, Khandekar J, Shikany JM, Satterfield S, Chlebowski RT (2007) Low-fat dietary pattern and cancer incidence in the Women’s Health Initiative Dietary Modification Randomized Controlled Trial. J Natl Cancer Inst:djm159Google Scholar
  26. 26.
    Howard BV, Van Horn L, Hsia J, Manson JE, Stefanick ML, Wassertheil-Smoller S, Kuller LH, LaCroix AZ, Langer RD, Lasser NL, Lewis CE, Limacher MC, Margolis KL, Mysiw WJ, Ockene JK, Parker LM, Perri MG, Phillips L, Prentice RL, Robbins J, Rossouw JE, Sarto GE, Schatz IJ, Snetselaar LG, Stevens VJ, Tinker LF, Trevisan M, Vitolins MZ, Anderson GL, Assaf AR, Bassford T, Beresford SA, Black HR, Brunner RL, Brzyski RG, Caan B, Chlebowski RT, Gass M, Granek I, Greenland P, Hays J, Heber D, Heiss G, Hendrix SL, Hubbell FA, Johnson KC, Kotchen JM (2006) Low-fat dietary pattern and risk of cardiovascular disease: the Women’s Health Initiative Randomized Controlled Dietary Modification Trial. JAMA 295:655–666PubMedCrossRefGoogle Scholar
  27. 27.
    Mensink RP, Katan MB (1992) Effect of dietary fatty acids on serum lipids and lipoproteins. A meta-analysis of 27 trials. Arterioscler Thromb 12:911–919PubMedGoogle Scholar
  28. 28.
    Kim EH, Willett WC, Colditz GA, Hankinson SE, Stampfer MJ, Hunter DJ, Rosner B, Holmes MD (2006) Dietary fat and risk of postmenopausal breast cancer in a 20-year follow-up. Am J Epidemiol 164:990–997PubMedCrossRefGoogle Scholar
  29. 29.
    Cho E, Spiegelman D, Hunter DJ, Chen WY, Stampfer MJ, Colditz GA, Willett WC (2003) Premenopausal fat intake and risk of breast cancer. J Natl Cancer Inst 95:1079–1085PubMedGoogle Scholar
  30. 30.
    van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, Folsom AR, Fraser G, Goldbohm RA, Graham S, Kushi L, Marshall JR, Miller AB, Rohan T, Smith-Warner SA, Speizer FE, Willett WC, Wolk A, Hunter DJ (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152:514–527PubMedCrossRefGoogle Scholar
  31. 31.
    Ahlgren M, Melbye M, Wohlfahrt J, Sorensen TI (2004) Growth patterns and the risk of breast cancer in women. N Engl J Med 351:1619–1626PubMedCrossRefGoogle Scholar
  32. 32.
    Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE (2006) Adult weight change and risk of postmenopausal breast cancer. JAMA 296:193–201PubMedCrossRefGoogle Scholar
  33. 33.
    Knopp RH, Walden CE, Retzlaff BM, McCann BS, Dowdy AA, Albers JJ, Gey GO, Cooper MN (1997) Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men. The Dietary Alternatives Study. JAMA 278:1509–1515PubMedCrossRefGoogle Scholar
  34. 34.
    Chlebowski RT, Blackburn GL, Thomson CA, Nixon DW, Shapiro A, Hoy MK, Goodman MT, Giuliano AE, Karanja N, McAndrew P, Hudis C, Butler J, Merkel D, Kristal A, Caan B, Michaelson R, Vinciguerra V, Del Prete S, Winkler M, Hall R, Simon M, Winters BL, Elashoff RM (2006) Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women’s Intervention Nutrition Study. J Natl Cancer Inst 98:1767–1776PubMedCrossRefGoogle Scholar
  35. 35.
    Pierce JP, Natarajan L, Caan BJ, Parker BA, Greenberg ER, Flatt SW, Rock CL, Kealey S, Al-Delaimy WK, Bardwell WA, Carlson RW, 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) Influence of a diet very high in vegetables, fruit, and fiber and low in fat on prognosis following treatment for breast cancer: the Women’s Healthy Eating and Living (WHEL) Randomized Trial. JAMA 298:289–298PubMedCrossRefGoogle Scholar
  36. 36.
    Jackson RD, LaCroix AZ, Gass M, Wallace RB, Robbins J, Lewis CE, Bassford T, Beresford SA, Black HR, Blanchette P, Bonds DE, Brunner RL, Brzyski RG, Caan B, Cauley JA, Chlebowski RT, Cummings SR, Granek I, Hays J, Heiss G, Hendrix SL, Howard BV, Hsia J, Hubbell FA, Johnson KC, Judd H, Kotchen JM, Kuller LH, Langer RD, Lasser NL, Limacher MC, Ludlam S, Manson JE, Margolis KL, McGowan J, Ockene JK, O’Sullivan MJ, Phillips L, Prentice RL, Sarto GE, Stefanick ML, Van Horn L, Wactawski-Wende J, Whitlock E, Anderson GL, Assaf AR, Barad D (2006) Women’s Health Initiative Investigators. Calcium plus vitamin D supplementation and the risk of fractures. N Engl J Med 354:669–683PubMedCrossRefGoogle Scholar
  37. 37.
    Writing Group for the Women’s Health Initiative I (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative Randomized Controlled Trial. JAMA 288:321–333CrossRefGoogle Scholar
  38. 38.
    The Women’s Health Initiative Steering C (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative Randomized Controlled Trial. JAMA 291:1701–1712CrossRefGoogle Scholar
  39. 39.
    Mendelsohn ME, Karas RH (2007) HRT and the young at heart. N Engl J Med 356:2639–2641PubMedCrossRefGoogle Scholar
  40. 40.
    Rossouw JE, Anderson GL, Prentice RL, LaCroix AZ, Kooperberg C, Stefanick ML, Jackson RD, Beresford SA, Howard BV, Johnson KC, Kotchen JM, Ockene J (2002) Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women’s Health Initiative Randomized Controlled Trial. JAMA 288:321–333PubMedCrossRefGoogle Scholar
  41. 41.
    Anderson GL, Limacher M, Assaf AR, Bassford T, Beresford SA, Black H, Bonds D, Brunner R, Brzyski R, Caan B, Chlebowski R, Curb D, Gass M, Hays J, Heiss G, Hendrix S, Howard BV, Hsia J, Hubbell A, Jackson R, Johnson KC, Judd H, Kotchen JM, Kuller L, LaCroix AZ, Lane D, Langer RD, Lasser N, Lewis CE, Manson J, Margolis K, Ockene J, O’Sullivan MJ, Phillips L, Prentice RL, Ritenbaugh C, Robbins J, Rossouw JE, Sarto G, Stefanick ML, Van Horn L, Wactawski-Wende J, Wallace R, Wassertheil-Smoller S (2004) Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women’s Health Initiative Randomized Controlled Trial. JAMA 291:1701–1712PubMedCrossRefGoogle Scholar
  42. 42.
    Manson JE, Hsia J, Johnson KC, Rossouw JE, Assaf AR, Lasser NL, Trevisan M, Black HR, Heckbert SR, Detrano R, Strickland OL, Wong ND, Crouse JR, Stein E, Cushman M (2003) Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med 349:523–534PubMedCrossRefGoogle Scholar
  43. 43.
    Grodstein F, Manson JE, Stampfer MJ (2006) Hormone therapy and coronary heart disease: the role of time since menopause and age at hormone initiation. J Womens Health (Larchmt) 15:35–44CrossRefGoogle Scholar
  44. 44.
    Stefanick ML, Anderson GL, Margolis KL, Hendrix SL, Rodabough RJ, Paskett ED, Lane DS, Hubbell FA, Assaf AR, Sarto GE, Schenken RS, Yasmeen S, Lessin L, Chlebowski RT (2006) Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy. JAMA 295:1647–1657PubMedCrossRefGoogle Scholar
  45. 45.
    Chen WY, Manson JE, Hankinson SE, Rosner B, Holmes MD, Willett WC, Colditz GA (2006) Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med 166:1027–1032PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  1. 1.Department of Obstetrics, Gynecology and Reproductive Biology, Obstetrics and Gynecology Epidemiology CenterBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  2. 2.Channing Laboratory, Department of MedicineBrigham and Women’s Hospital, Harvard Medical SchoolBostonUSA
  3. 3.Department of EpidemiologyHarvard School of Public HealthBostonUSA
  4. 4.Department of NutritionHarvard School of Public HealthBostonUSA

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