Dietary Fat and Breast Cancer: Testing Interventions to Reduce Risks

  • Johanna T. Dwyer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 322)


The presentation discusses the issue of testing dietary interventions in post-menopausal breast cancer prevention. The many dietary hypotheses that might be tested are very briefly summarized. For illustrative purposes, the progress made in feasibility studies of the Women’s Health Trial, a low-fat intervention study to decrease incidence of breast cancer in post-menopausal women at increased risk of cancer of the breast is used. Results of several other similar interventions to test the fat hypothesis are also reviewed, including the Nutrition Adjuvant Study, the WINS study, the Swedish breast cancer trial, a Canadian study conducted at the Ludwig Institute, and a possible study by the American Cancer Society. Some research questions that arise in testing dietary interventions are discussed. These include underlying assumptions about mechanisms, and controlling errors, particularly response errors. Practical issues such as how to measure adherence in the absence of a good biologic marker are also addressed. The review concludes with a section on future research and action directions.


Breast Cancer Breast Cancer Risk Energy Intake Food Group Natl Cancer Inst 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    U.S. Department of Health and Human Services, “Steroid Receptors in Breast Cancer: Information for Physicians,” NIH Pub. No 83:1853 National Cancer Institute, Bethesda, August (1983).Google Scholar
  2. 2.
    Early breast cancer trialists collaborative group effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer: an overview of 61 randomized trials among 38,896 women, N Engl J Med. 319: 1681 (1988).Google Scholar
  3. 3.
    T. Pomander, B. Cedarmark, A. Mattsson, L. Skoog, T. Theve, J. Askergrein, L.E. Rutqvist, U. Glas, C. Silversward, A. Somell, N. Wilking, and M.L. Hjalmar, Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers, Lancet. 1: 117 (1989).Google Scholar
  4. 4.
    D.T. Kiang, Chemoprevention for breast cancer: are we ready?, J Natl Cancer Inst. 83: 462 (1991).PubMedGoogle Scholar
  5. 5.
    J.W. Weisburger and E.L. Wynder, Dietary fat intake and cancer, Hematology/Oncology Clinics of North America. 5: 7 (1991).PubMedGoogle Scholar
  6. 6.
    L.A. Cohen, M.E. Kendall, E. Zang, C. Meschter, and D.P. Rose, Modulation of N-Nitrosomethylurea induced mammary tumor promotion by dietary fiber and fat, J Natl Cancer Inst. 83: 496 (1991).PubMedCrossRefGoogle Scholar
  7. 7.
    R.L. Prentice and L. Sheppard, Dietary fat and cancer: consistency of the epidemiologic data and disease prevention that may follow from a practical reduction in fat consumption, Cancer Causes and Control. 1: 81 (1990).PubMedCrossRefGoogle Scholar
  8. 8.
    R.L. Prentice and L. Sheppard, Dietary fat and cancer: rejoinder and discussion of research strategies, Cancer Causes and Control. 2: 53 (1990).CrossRefGoogle Scholar
  9. 9.
    W.C. Willett and M. Stampfer, Dietary fat and cancer: another view, Cancer Causes and Control. 1:103 (1990).CrossRefGoogle Scholar
  10. 10.
    G.R. Howe, Dietary fat and cancer, Cancer Causes and Control. 1: 99 (1990).CrossRefGoogle Scholar
  11. 11.
    J.E. Hiller, and A.J. McMichael, Dietary fat and cancer: a comeback for etiological studies? Cancer Causes and Control. 1: 101 (1990).CrossRefGoogle Scholar
  12. 12.
    J.R. Hebert, J. Barone, M.M. Reddy, and J.Y. Backlund, Natural killer cell activity in a longitudinal dietary fat intervention trial, Clin Immunol Immunopathol. 54: 103 (1989).CrossRefGoogle Scholar
  13. 13.
    J. Barone, J.R. Hebert, and M.M. Reddy, Dietary fat and natural killer cell activity, Am J Clin Nutr. 50: 861 (1989).PubMedGoogle Scholar
  14. 14.
    Subcommittee on Nutritional Surveillance, Committee on Medical Aspect of Food Policy, The diets of British schoolchildren, Rep Health Soc Subj. (Lond) 36: 1–293 (1989).Google Scholar
  15. 15.
    H.P. Lee, L. Gouley, S.W. Duffy, J. Esteve, J. Lee, and N.E. Day, Dietary effects on breast cancer risk in Singapore, Lancet. 337: 1197 (1991).PubMedCrossRefGoogle Scholar
  16. 16.
    L.D. Byham, Dietary fat and natural killer cell function, Nutrition Today. Jan/Feb 31 (1991).Google Scholar
  17. 17.
    E.L. Wynder, L.A. Cohen, and D.P. Rose, Etiology of breast cancer: dietary fat and weight, Nutrition. 5: 361 (1989).PubMedGoogle Scholar
  18. 18.
    K.J. Acheson, I.T. Campbell, O.G.H. Edholm, D.S. Miller, and M.J. Stock, The measurement of daily energy expenditure: an evaluation of some techniques, Am J Clin Nutr. 33: 1155 (1980).PubMedGoogle Scholar
  19. 19.
    J.S. Stem, L. Grivetti, and T.W. Castonguay, Energy intake: uses and misuses, In J Obes. 8: 535 (1984).Google Scholar
  20. 20.
    M.B.E. Livingstone, A.M. Prentice, J.J. Strain, W.A. Coward, A.E. Black, M.E. Barker, P.G. McKenna, and R.G. Whitehead, Accuracy of weighed dietary records in studies of diet and health, Brit Med J. 300: 708 (1990).PubMedCrossRefGoogle Scholar
  21. 21.
    J.R. Hebert, A. Augustin, J. Barone, G.C. Kabat, D.W. Kinne, and E.L. Wynder, Weight, height, and body mass index in the prognosis of breast cancer: early results of a prospective study, Int J Cancer. 42: 315 (1988).PubMedCrossRefGoogle Scholar
  22. 22.
    L.J. Vattan and L. Kvinnsland, Body height and risk for breast cancer: a prospective study of 23,831 Norwegian women, Br J Cancer. 61: 881 (1990).CrossRefGoogle Scholar
  23. 23.
    G. Wilcox, M.L. Wahlquist, H.G. Burger and G. Medley, Oestrogenic effects of plant foods in postmenopausal women, Br Med J. 301: 905 (1990).CrossRefGoogle Scholar
  24. 24.
    M. Messina and S. Barnes, The role of soy products in reducing risk of cancer, J Natl Cancer Inst. 83: 541 (1991).PubMedCrossRefGoogle Scholar
  25. 25.
    P.P. Nair, N. Turjman, G. Kessie, B. Calkins, G.T. Goodman, H. Davidovitz, and G. Nimmagadda, Diet, nutrition intake, and metabolism in populations at high and low risk for colon cancer: dietary cholesterol, beta sitosterol, and stigmasterol, Am J Clin Nutr. 40: 927 (1984).PubMedGoogle Scholar
  26. 26.
    K Hirai, C. Shimazu, R. Takazoe, Y. Ozek, Cholesterol, phytosterol, and polyunsaturated fatty acid levels in 1982 and 1957 Japanese diets, J Nutr Sci Vitamin. 32: 363 (1986).CrossRefGoogle Scholar
  27. 27.
    A. Shatzkin, Y. Jones, R.N. Hoover, P.R. Taylor, L.A. Brinton, R.G. Ziegler, E.B. Harvey, C.L. Carter, L.M. Licitra, M.C. Dufour, and D.B. Larson, Alcohol consumption and breast cancer in the epidemiologic follow up study of the first National Health and Nutrition Examination Survey, N Engl J Med. 316: 1169 (1987).CrossRefGoogle Scholar
  28. 28.
    W.C. Willett, M.J. Stampfer, G.A. Colditz, B.A. Rosner, C.H. Hennedens, and F.E. Speizer, Moderate alcohol consumption and risk of breast cancer, N Engl J Med. 316: 1174 (1987).PubMedCrossRefGoogle Scholar
  29. 29.
    M.P. Longenecker, J.A. Berlin, M.J. Orza, and T.C. Chalmers, A metaanalysis of alcohol consumption in relation to risk of breast cancer, J Amer Med Assoc. 260: 652 (1988).CrossRefGoogle Scholar
  30. 30.
    J.W.G. Yarnell, A.M. Fehily, J.E. Milbank, P.M. Sweetnam, and C.L. Walker, A short dietary questionnaire for use in an epidemiological survey: comparison with weighed dietary records, Hum Nutr Appl Nutr. 37A: 103 (1983).PubMedGoogle Scholar
  31. 31.
    J.R. Hebert and G.C. Kabat, Distribution of smoking and its association with lung cancer: implications for studies on the association of fat with cancer, J Natl Cancer Inst. 83: 872 (1991).PubMedCrossRefGoogle Scholar
  32. 32.
    C.T. Windham, B.W. Wyse, and R.G. Hansen, Alcohol consumption and nutrient density of diets in the Nationwide Food Consumption Survey, J Am Diet Assoc. 82: 364 (1983).PubMedGoogle Scholar
  33. 33.
    D.P. Rose, A.P. Boyar, and E.L. Wynder, International comparisons of mortality rates for cancer of the breast, ovary, prostate, and colon, and per capita food consumption, Cancer. 58: 23–63 (1986).CrossRefGoogle Scholar
  34. 34.
    D.M. Goettler, L. Levin, and W.Y. Chey, Postprandial levels of prolactin and gut hormones in breast cancer patients: association with stage of disease, but not dietary fat, J Natl Cancer Inst. 82: 22 (1990).PubMedCrossRefGoogle Scholar
  35. 35.
    R Hill, E.L. Wynder, and P. Heiman, Plasma hormone levels in premenopausal and postmenopausal vegetarian women fed a Western diet, Fed Proc. 38: 865 (1979).Google Scholar
  36. 36.
    R Hill, J.H. Thijssen, L. Garbaczewski, P.F. Koppeschaar, and F. De Waard, VIP and prolactin release in response to meals, Scand J Gastroenteral. 21: 958 (1986).CrossRefGoogle Scholar
  37. 37.
    M.A. Hagerty, B. Howie, S. Tan, and T.D. Shultz, Effect of low and high fat intakes on hormone levels in premenopausal women: a controlled metabolic feeding study, Fed Proc. 47: 653 (1988).Google Scholar
  38. 38.
    D.M. Ingram, P.C. Bennett, D. Willcox, and N. De Klerk, Effect of low fat diet on female sex hormone levels, J Natl Cancer Inst. (1987).Google Scholar
  39. 39.
    R.L. Prentice, F. Kakar, S. Hursting, L. Sheppard, R. Klein, and L.H. Kushi, Aspects of the rationale for the Women’s Health Trial, J Natl Cancer Inst. 80: 802 (1988).PubMedCrossRefGoogle Scholar
  40. 40.
    R.L. Prentice and L. Sheppard, Validity of international, time trend, and migrant studies of dietary factors and disease risk, Prey Med. 18: 167 (1989).CrossRefGoogle Scholar
  41. 41.
    R.T. Chlebowski, D.W. Nixon, G.L. Blackburn, P. Jochimsen, E.F. Scanlon, W. Insull, I.M. Buzzard, R. Elashoff, R. Butrum, and E.L. Wynder, Breast cancer nutrition adjuvant study (NAS): protocol design and initial patient adherence, Breast Cancer Res Treat. 10: 21 (1987).PubMedCrossRefGoogle Scholar
  42. 42.
    I.M. Buzzard, E.H. Asp, R.T. Chlebowski, A.P. Boyar, R.W. Jeffrey, D.W. Nixon, G.L. Blackburn, P.R. Jochimsen, E.F. Scanlon, W. Insull, R.M. Elashoff, R. Butrum, and E.L. Wynder, Diet intervention methods to reduce fat intake: nutrient and food group composition of self selected low fat diets, J Am Diet Assoc. 90: 42 (1990).PubMedGoogle Scholar
  43. 43.
    R.T. Chlebowski, G.L. Blackburn, and I.M. Buzzard. Current status: Evaluation of dietary fat reduction as secondary breast cancer prevention, in: “Advances in cancer control: Screening and Prevention Research,” Wiley Liss, Inc. (1990).Google Scholar
  44. 44.
    R.T. Chlebowski, G.L. Blackburn, and D.W. Nixon, P. Jochimsen, E.F. Scanlon, W. Insull, I.M. Buzzard, E.L. Wynder, and R. Elashoff, The nutrition adjuvant study experience and commentary, Controlled Clinical Trials. 10: 368 (1989).PubMedCrossRefGoogle Scholar
  45. 45.
    R.T. Chlebowski and D. Rose, Adjuvant dietary fat intake reduction in postmenopausal breast cancer management (1991).Google Scholar
  46. 46.
    A.P. Boyar, D.P. Rose, and E.L. Wynder, Recommendations for the prevention of chronic disease: the application for breast disease, Am J Clin Nutr. 48: 896 (1988).PubMedGoogle Scholar
  47. 47.
    H. Lee-Han, M. Cousins, M. Beaton, V. McGuire, Y. Driudov, M. Chipman, and N. Boyd, Compliance in a randomized clinical trial of dietary fat reduction in patients with breast dysplasia, Am J Clin Nutr. 48: 575 (1988).PubMedGoogle Scholar
  48. 48.
    N.F. Boyd, M.L. Cousins, S.E. Bayliss, E.D. Fishell, and W.R. Bruce, Diet amp; Breast Disease: evidence for the feasibility of a clinical trial involving a major reduction in dietary fat, in: “Cancer Nutrient Eating Behavior,” T.G. Burish, S.M. Levy, and B.E. Meyerowitz, eds., Lawrence Earlbaum Associates, Inc., New York (1984).Google Scholar
  49. 49.
    M.G. Jain, G.R. Howe, K.C. Johnson, and A.B. Miller, Evaluation of a diet history questionnaire for epidemiologic studies, Am J Epidemiol. 111: 2112 (1980).Google Scholar
  50. 50.
    M.J. Jain, L. Harrison, G.R. Howe, and A.B. Miller, Evaluation of a self administered dietary questionnaire for use in a cohort study, Am J Clin Nutr. 36: 931 (1982).PubMedGoogle Scholar
  51. 51.
    R.W. Morgan, M. Jain, A.B. Miller, N.W. Choi, W. Matthews, L. Munan, J.D. Burch, J. Feather, G.R. Howe, and A. Kelly, Comparison of dietary methods in an epidemiologic study, Am J Epidemiol. 107: 488 (1978).PubMedGoogle Scholar
  52. 52.
    G.R. Howe, C.M. Friedenreich, M. Jain, and A.B. Miller, A cohort study of fat intake and risk factors of breast cancer, J Nall Cancer Inst. 83: 336 (1991).CrossRefGoogle Scholar
  53. 53.
    G.R. Howe, T. Hirohata, T.G. Hislap J.M. Iscovich, J.M. Yuan, K. Katsouyanni, F. Lubin, E. Marubini, B. Modan, T. Rohan, P. Toniolo, and Y. Shunzhang, Dietary factors and risk of breast cancer, J Natl Cancer Inst. 83: 336 (1991).PubMedCrossRefGoogle Scholar
  54. 54.
    G.R. Howe, Response, J Natl Cancer Inst. 83: 1035 (1991).Google Scholar
  55. 55.
    P. Knekt, D. Albanes, R. Seppanen, A. Aromaa, R. Jarvinen, L. Hyvonen, L. Teppo, and E. Pukkala, Dietary fat and risk of breast cancer, Am J Clin Nutr. 52: 903 (1990).PubMedGoogle Scholar
  56. 56.
    P.K. Mills, W.L. Beeson, R.L. Philips, and G.E. Fraser, Dietary habits and breast cancer incidence among Seventh day Adventists, Cancer. 64: 582 (1989).PubMedCrossRefGoogle Scholar
  57. 57.
    J.R. Hebert and G.C. Kabat, Implications for cancer epidemiology of differences in dietary intake associated with alcohol consumption, Nutrition and Cancer. 15: 107 (1991).PubMedCrossRefGoogle Scholar
  58. 58.
    W. Willett and M.J. Stampfer, Total energy intake: implications for epidemiologic analyses, Am J Epidemiol. 124: 17 (1986).PubMedGoogle Scholar
  59. 59.
    M.C. Pike, L. Bernstein, and R.K. Feters, Letter to the editor, Am J Epidemiol. 129: 1312 (1989).PubMedGoogle Scholar
  60. 60.
    T.E. Prewitt, D. Schmeisser, P.E. Bowen, P. Aye, T.A. Dolecek, T. Langenberg, T. Cole, and L. Brace, Changes in body weight, body composition, and energy intake in women fed high and low fat diets, Am J Clin Nutr. 54: 304 (1991).PubMedGoogle Scholar
  61. 61.
    G. Block, A.M. Hartman, C.M. Dresser, M.D. Carroll, J. Cannon, and L. Gardner, A data based approach to diet questionnaire design and testing, Am J Epidemiol. 124: 453 (1986).PubMedGoogle Scholar
  62. 62.
    R.S. Gibson, “Principles of Nutritional Assessment” Oxford University Press, New York (1990).Google Scholar
  63. 63.
    S. Bingham, The dietary assessment of individuals: methods, accuracy, new techniques, and recommendations, Nut Abst and Rev. 57: 707 (1987).Google Scholar
  64. 64.
    E.M. Pao and Y.S. Cypel, Estimation of dietary intake, in: “Present Knowledge in Nutrition: M.L. Brown, ed., International Life Sciences Institute, Washington, (1990).Google Scholar
  65. 65.
    E.M. Pao, K.E. Sykes, and Y.S. Cypel, USDA Methodological Research for Large Scale Dietary Intake Surveys, 1975–88 Washington United States Department of Agriculture, Human Nutrition Information Service, Home Economics Research Report Number 49 (1989).Google Scholar
  66. 66.
    G. Block and A.M. Hartman, Dietary Methods, in: “Nutrition and Cancer Prevention,” T.E. Moon and M.S. Micozzi, eds. Marcel Dekkar, New York (1989).Google Scholar
  67. 67.
    D. Mackerras, Interpreting Dietary Data, Sydney Department of Public Health, University of Sydney (1990).Google Scholar
  68. 68.
    J.T. Dwyer, Assessment of dietary intake, in: “Modem Nutrition in Health and Disease” M.E. Shils and V. R. Young, eds. Philadelphia (1988).Google Scholar
  69. 69.
    M.N. Woods, S.L. Gorbach, C. Longscope, B.R. Goldin, J.T. Dwyer, and A. MorrillLaBrode, Low fat high fiber and serum estrone sulfate in premenopausal women, Am J Clin Nutr. 49: 1179 (1989).PubMedGoogle Scholar
  70. 70.
    W. Insull, M.M. Henderson, R.L. Prentice, D.J. Thompson, C. Clifford, S. Goldman, S. Gorbach, M. Moskowitz, R. Thompson, and M. Woods, Results of a randomized feasibility study of a low fat diet, Arch Intern Med. 150: 421 (1990).PubMedCrossRefGoogle Scholar
  71. 71.
    R.L. Prentice, D.J. Thompson, C. Clifford, S.L. Gorbach, B. Goldin, and D. Byar, Dietary fat reduction and plasma estradiol concentration in healthy postmenopausal women, J Natl Cancer Inst. 82: 129 (1990).PubMedCrossRefGoogle Scholar
  72. 72.
    S.A. Bingham, M. Nelson, and A.A. Paul, Methods for data collection at the individual level, in: “Manual on Methodology For Food Consumption Studies,” M. Cameron and V. Staveren, eds.. Oxford University Press, Oxford (1988).Google Scholar
  73. 73.
    J.J. Michnovicz and H.L. Bradlow, Induction of estradiol metabolism by dietary indole 3carbinol in humans, J Natl Cancer Inst. 82: 947 (1990).PubMedCrossRefGoogle Scholar
  74. 74.
    N.L. Petrakis, L.D. Gruenke, and J.C. Craig, Cholesterol and cholesterol epoxides in nipple aspirates on human breast fluid, Cancer Res. 41: 2563 (1981).PubMedGoogle Scholar
  75. 75.
    L.A. Cohen, K. Choi, J.H. Weisburger, and D.P. Rose, Effect of varying dietary fat on the development of N-nitrosoethylurea induced in rat mammary tumors, Anticancer Res. 6: 215 (1986).PubMedGoogle Scholar
  76. 76.
    L.A. Cohen and E.L. Wynder, Do dietary monosaturated fatty acids play a protective role in carcinogenesis and cardiovascular disease?, Med Hypothesis. 31: 83 (1990).CrossRefGoogle Scholar
  77. 77.
    A. Morabia and E.L. Wynder, Epidemiology and natural history of breast cancer: implications for the body weight-breast cancer controversy, Surgical Clinics of North America. 70: 739 (1991).Google Scholar
  78. 78.
    H. Aldercreutz, T. Fotsis, R. Heikkinen, J.T. Dwyer, B.R. Goldin, S.L. Gorbach, A.M. Lawson, and K.D.R. Setchell, Diet and urinary excretion of lignan in female subjects, Med Biol. 59: 259 (1981).Google Scholar
  79. 79.
    H. Aldercreutz, T. Fotsis, R. Heikkinen, J.T. Dwyer, M. Woods, B.R. Goldin, and S.L. Gorbach, Excretion of the lignans anterolectone and enterodiol and of equol in omnivorous and vegetarian postmenopausal women with breast cancer, Lancet. ii: 1295 (1982).Google Scholar
  80. 80.
    H. Adlercreutz, T. Fotsis, C. Bannwart, K. Wahala, T. Makela, G. Brunow, and T. Hase, Determination of urinary lignans and phytoestrogen metabolites, potential antiestrogens and anticarcinogens in urine of women on various habitual diets, J Steroid Biochem. 25: 791, (1986).PubMedCrossRefGoogle Scholar
  81. 81.
    E. Nordevang, E. Ikkala, E. Callmer, L. Hallstrom, and L.E. Holm, Dietary intervention in breast cancer patients: effects on dietary habits and nutrient intake, European J Clin Nutr. 44: 681 (1990).Google Scholar
  82. 82.
    A.P. Boyar, D.P. Rose, J. Loughridge, A. Engle, A. Palgi, K. Laakso, D. Kinne, and E.L. Wynder, Response to a diet low in total fat in women with postmenopausal breast cancer, Nutr Cancer. 11: 93 (1988).PubMedCrossRefGoogle Scholar
  83. 83.
    S.L. Gorbach, A. Morrill-LaBrode, M.N. Woods, J.T. Dwyer, W.D. Selles, M. Henderson, W. Insult, S. Goldman, D. Thompson, C. Clifford, and L. Sheppard, Changes in food patterns during a low fat dietary intervention in women, J Am Diet Assoc. 90: 802 (1990).PubMedGoogle Scholar
  84. 84.
    M.E. Cameron and W.A Van Stavaran, eds., “Manual on Methodology for Food Consumption Studies” Oxford University Press, Oxford, (1988).Google Scholar

Copyright information

© Plenum Press, New York 1992

Authors and Affiliations

  • Johanna T. Dwyer
    • 1
  1. 1.Frances Stern Nutrition CenterNew England Medical Center HospitalsBostonUSA

Personalised recommendations