Breast Cancer Research and Treatment

, Volume 20, Issue 2, pp 73–84 | Cite as

Adjuvant dietary fat intake reduction in postmenopausal breast cancer patient management

  • Rowan T. Chlebowski
  • David Rose
  • I. Marilyn Buzzard
  • George L. Blackburn
  • William InsullJr.
  • Mary Grosvenor
  • Robert Elashoff
  • Ernst L. Wynder
  • For the Women's Intervention Nutrition Study (WINS)


Management of localized breast cancer now commonly involves a breast-sparing approach combined with systemic adjuvant therapy resulting in improved cosmetic results and patient survival. Reducing dietary fat intake represents a conceptually new approach to further improve outcome of patients with resected breast cancer. The rationale supporting evaluation of dietary fat reduction in the management of patients with localized breast cancer is based on: (1) epidemiologic observations (along with biochemical and hormonal correlates) of major differences in stage-by-stage survival of patients with localized breast cancer comparing outcome in countries with low fat (Japan) versus high fat (U.S.A.) dietary intakes; (2) relationships between dietary fat intake and factors prognostic of clinical outcome in patients with established breast cancer; (3) effects of weight gain (especially that associated with adjuvant chemotherapy) on breast cancer clinical outcome; (4)in vivo animal studies demonstrating adverse influence of increased dietary fat intake (especially linoleic acid) on growth and metastatic spread of mammary cancer; (5) direct adverse effects of increased linoleic acid on human breast cancer growthin vitro; (6) plausible mechanisms which could mediate the effects of dietary fat intake reduction on breast cancer growth and metastatic spread; (7) demonstration of adherence to dietary fat reduction regimens in ongoing clinical feasibility studies including those involving postmenopausal patients with resected breast cancer; and (8) favorable sample size requirements for definitive assessment of dietary fat intake reduction influence on breast cancer growth and metastases (using as endpoints relapse-free survival and overall survival) in postmenopausal breast cancer patients with localized disease.

Key words

dietary fat breast cancer recurrence linoleic acid 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Adams LM, Trout JR, Karmali RA: Effect of n-3 fatty acids on spontaneous and experimental metastasis of rat mammary tumor 13762. Br J Cancer 61: 290–291, 1990PubMedGoogle Scholar
  2. 2.
    Armstrong B, Doll R: Environmental factors and cancer incidence and mortality in different countries, with special reference to dietary practice. Int J Cancer 15: 617–631, 1975PubMedGoogle Scholar
  3. 3.
    Bonadonna G, Valagussa P, Rossi A,et al.: Ten-year experience with CMF-based adjuvant chemotherapy in resectable breast cancer. Breast Cancer Res Treat 5: 95–115, 1985PubMedGoogle Scholar
  4. 4.
    Bonomi P, Bunting N, Fishman D,et al.: Weight gain during adjuvant chemotherapy or hormone-chemotherapy for stage II breast cancer evaluated in relation to disease free survival. Breast Cancer Res Treat 4: 339, 1984Google Scholar
  5. 5.
    Boyar AP, Rose DP, Loughrige JR,et al.: Response to diet low in total fat in women with postmenopausal breast cancer. A pilot study. Nutr Cancer 11: 93–99, 1988PubMedGoogle Scholar
  6. 6.
    Boyar AP, Rose DP, Wynder EL: Recommendations for the prevention of chronic disease: the application for breast cancer. Am J Clin Nutr 48: 896–900, 1988PubMedGoogle Scholar
  7. 7.
    Boyd NF, Campbell JE, Germanson T,et al.: Body weight and prognosis in breast cancer. J Natl Cancer Inst 67: 785–789, 1981PubMedGoogle Scholar
  8. 8.
    Boyd NF, McGuire V: Evidence of association between plasma high-density lipoprotein cholesterol and risk factors for breast cancer. J Natl Cancer Inst 82: 460–468, 1990PubMedGoogle Scholar
  9. 9.
    Boyd NF, McGuire V, Shannon P,et al.: Effect of a low-fat, high carbohydrate diet on symptoms of cyclical mastopathy. Lancet 2: 128–132, 1988PubMedGoogle Scholar
  10. 10.
    Buckman DK, Chapkin RS, Erickson KL: Modulation of mouse mammary tumor growth and linoleate-enhanced metastasis by oleate. J Nutr 120: 148–157, 1990PubMedGoogle Scholar
  11. 11.
    Buckman DK, Erickson KL, Ross BD: Dietary fat modulation of murine mammary tumor metabolism studiedin vivo with 31P-nuclear magnetic resonance spectroscopy. Cancer Res 47: 5631–5636, 1987PubMedGoogle Scholar
  12. 12.
    Buzzard IM, Asp EH, Chlebowski RT,et al.: Diet intervention methods to reduce fat intake: Nutrient and food group composition of self-selected low-fat diets. J Amer Diet Assoc 90: 42–53, 1990Google Scholar
  13. 13.
    Camoriano JK, Loprinizi CL, Ingle JN: Weight change in women treated with adjuvant therapy or observed following mastectomy for node-positive breast cancer. J Clin Oncol 8: 1327–1334, 1990PubMedGoogle Scholar
  14. 14.
    Chlebowski RT, Weiner JM, Reynold R,et al.: Long-term survival following relapse after 5-FU but not CMF adjuvant breast cancer therapy. Breast Cancer Res Treat 7: 23–29, 1986PubMedGoogle Scholar
  15. 15.
    Chlebowski RT, Nixon DW, Blackburn GL,et al.: A breast cancer Nutrition Adjuvant Study (NAS): Protocol design and initial patient adherence. Breast Cancer Res Treat 10: 21–29, 1987PubMedGoogle Scholar
  16. 16.
    Chlebowski RT, Blackburn GL, Buzzard IM,et al.: Current status: evaluation of dietary fat reduction in secondary breast cancer prevention. In: Engstrom P (ed) Advances in Cancer Control VII. Alan R. Liss, Inc., New York, 1989Google Scholar
  17. 17.
    Cohen LA, Thompson DO, Choi K,et al.: Dietary fat and mammary cancer II. Modulation of serum and tumor lipid composition and tumor prostaglandins by different dietary fat: associations with tumor incidence patterns. J Natl Cancer Inst 77: 43–51, 1986PubMedGoogle Scholar
  18. 18.
    DeConti R: Weight gain in the adjuvant chemotherapy of breast cancer. Proc Am Soc Clin Oncol 1: 73, 1982Google Scholar
  19. 19.
    Dixon J, Moritz DA, Baker FL: Breast cancer and weight gain: An unexpected finding. Oncol Nurs Forum 5: 5–7, 1978Google Scholar
  20. 20.
    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 28,396 women. N Eng J Med 319: 1681–1692, 1988Google Scholar
  21. 21.
    Erickson KL: Dietary fat modulation of immune response. Int J Immunopharmacol 8: 529–543, 1986PubMedGoogle Scholar
  22. 22.
    Erickson L, Hubbard NE: Dietary fat and tumor metastasis. Nutr Rev 48: 6–12, 1990PubMedGoogle Scholar
  23. 23.
    Fentiman IS: The endocrine prevention of breast cancer. Br J Cancer 38: 1–7, 1989Google Scholar
  24. 24.
    Fisher B, Bauer M, Margolese R,et al.: Five year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer. N Engl J Med 312: 665, 1985PubMedGoogle Scholar
  25. 25.
    Foltz AT: Weight gain among stage II breast cancer patients: A study of five factors. Oncol Nurs Forum 12: 21–26, 1985Google Scholar
  26. 26.
    Fornander T, Cedermark B, Mattson A,et al.: Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancer. Lancet i: 117, 1989Google Scholar
  27. 27.
    Freter CE, Lippman ME, Cheville A,et al.: Alterations in phosphoinositide metabolism associated with 17-β estradiol and growth factor treatment of MCF-7 breast cancer cells. Mol Endocrinol 2: 159–166, 1988PubMedGoogle Scholar
  28. 28.
    Gabor H, Hillyard LA, Abraham S: Effect of dietary fat on growth kinetics of transplantable mammary adenocarcinoma in BALB/c mice. J Natl Cancer Inst 74: 1299–1305, 1985PubMedGoogle Scholar
  29. 29.
    Glasgow WC, Eling TE: Involvement of linoleic acid metabolites in epidermal growth factor-stimulated mitogenesis in Balb/c 3T3 fibroblasts. Proc Am Assoc Cancer Res 30: 102, 1989Google Scholar
  30. 30.
    Goldin BR, Adlercreutz H, Gorbach SL, Woods MN,et al.: The relationship between estrogen levels and diets of Caucasian American and Oriental immigrant women. Am J Clin Nutr 44: 945–953, 1986PubMedGoogle Scholar
  31. 31.
    Goodwin PJ, Panzarella T, Boyd NF: Weight gain in women with localized breast cancer — a descriptive study. Breast Cancer Res Treat 11: 59–66, 1988PubMedGoogle Scholar
  32. 32.
    Greenwald P: Strengths and limitations of methodologic approaches to the study of diet and cancer; summary and future perspectives with emphasis on dietary fat and breast cancer. Prev Med 18: 163–166, 1989PubMedGoogle Scholar
  33. 33.
    Gregorio DI, Emrich LJ, Graham S,et al.: Dietary fat consumption and survival among women with breast cancer. J Natl Cancer Inst 75: 37–41, 1985PubMedGoogle Scholar
  34. 34.
    Hayward JL, Greenwood FC, Glober G,et al.: Endocrine status in postmenopausal British, Japanese, and Hawaiian-Japanese women. Eur J Cancer 14: 1221–1229, 1978PubMedGoogle Scholar
  35. 35.
    Heasman KZ, Sutherland JH, Campbell JA,et al.: Weight gain during adjuvant chemotherapy for breast cancer. Breast Cancer Res Treat 5: 195–200, 1986Google Scholar
  36. 36.
    Henderson MM, Kushi LH, Thompson DJ, Gorbach SL, Clifford CK, Insull W Jr, Moskowitz M, Thompson RS: Feasibility of a randomized trial of a low-fat diet for the prevention of breast cancer. Prev Med 19: 115–133, 1990PubMedGoogle Scholar
  37. 37.
    Hill P, Wynder EL: Comparison of mammary adipose fatty acid composition in Japanese and American breast cancer patients. Eur J Cancer Clin Oncol 23: 407–410, 1987PubMedGoogle Scholar
  38. 38.
    Hillyard LA, Abraham S: Effect of dietary polyunsaturated fatty acids on growth of mammary adenocarcinoma in mice and rats. Cancer Res 39: 4430–4431, 1979Google Scholar
  39. 39.
    Hopkins GJ, West CE: Effect of dietary fats on the growth of a transplantable adenocarcinoma in C3HB mice. J Natl Cancer Inst 58: 753–756, 1977PubMedGoogle Scholar
  40. 40.
    Holm LE, Callmer E, Hjalmar ML,et al.: Dietary habits and prognostic factors in breast cancer. J Natl Cancer Inst 81: 1218–1223, 1989PubMedGoogle Scholar
  41. 41.
    Holm LE, Nordwang E, Ihkala E, Hallstrom L, Callmer E: Dietary intervention as adjuvant therapy in breast cancer patients — a feasibility study. Breast Cancer Res Treat 16: 103–109, 1990PubMedGoogle Scholar
  42. 42.
    Hoskin PJ, Ashley S, Yarnold JR: Changes in body weight after treatment for breast cancer and effect of Tamoxifen. Brit J Cancer 62: (Supl XI): 26, 1990Google Scholar
  43. 43.
    Howe GR, Hirohata T, Hislop TG, Iscovich JM,et al.: Dietary factors and risks of breast cancer: combined analysis of 12 case-control studies. J Natl Cancer Inst 82: 561–569, 1990PubMedGoogle Scholar
  44. 44.
    Hubbard NE, Erickson KL: Enhancement of metastasis from a transplantable mouse mammary tumor by dietary linoleic acid. Cancer Res 47: 6171–6175, 1987PubMedGoogle Scholar
  45. 45.
    Hubbard NE, Erickson KL: Effect of dietary linoleic acid on lodgement, proliferation, and survival of mammary tumor metastases. Cancer Lett 44: 117–125, 1989PubMedGoogle Scholar
  46. 46.
    Hulka BS: Dietary fat and breast cancer: case control and cohort studies. Prev Med 18: 180–193, 1989PubMedGoogle Scholar
  47. 47.
    Katz EB, Boylan ES: Stimulatory effect of a high polyunsaturated fat diet on lung metastasis from the 13762 mammary adenocarcinoma in the female retired breeder rats. J Natl Cancer Inst 79: 351–358, 1987PubMedGoogle Scholar
  48. 48.
    Katz EB, Boylan ES: Effect of the quality of dietary fat on tumor growth and metastasis from a rat mammary adenocarcinoma. Nutr Cancer 12: 343–350, 1989PubMedGoogle Scholar
  49. 49.
    Katz EB, Boylan ES: Effects of reciprocal changes of diets differing in fat content on pulmonary metastasis from the 13762 rat mammary tumor. Cancer Res 49: 2477–2484, 1989PubMedGoogle Scholar
  50. 50.
    Key TJA, Glen J, Wang DY,et al.: Sex hormones in women in rural China and in Britain. Br J Cancer 62: 631–636, 1990PubMedGoogle Scholar
  51. 51.
    Kollmorgen GM, Sanning WA, Lehman AA,et al.: Inhibition of lymphocyte function in rats fed high-fat diets. Cancer Res 39: 3458–3462, 1979PubMedGoogle Scholar
  52. 52.
    Kritchesky D: Nutrition and breast cancer. Cancer 66: 1321–1325, 1990PubMedGoogle Scholar
  53. 53.
    Kumaki T, Noguchi M, Tajiri K,et al.: Effects of high dietary fat on the total DNA and receptor contents in rats with 7,12-dimethylbenz[a]anthracene-induced mammary carcinoma. Breast Cancer Res Treat 14: 18, 1989Google Scholar
  54. 54.
    Lands WEM, Hamazaki T, Yamazaki K, Okeyander H,et al.: Changing dietary patterns. Am J Clin Nutr 51: 991–993, 1990PubMedGoogle Scholar
  55. 55.
    Lasekan JB, Ney DM: Mammary tumor lipids and plasma lipoproteins in DMBA-intiated rats fed olive or safflower oils. Nutr Cancer 14: 117–126, 1990PubMedGoogle Scholar
  56. 56.
    Lee-Han H, Cousins M, Beaton M,et al.: Compliance in a randomized clinical trial of dietary fat reduction in patients with breast dysplasia. Am J Clin Nutr 48: 575, 1988PubMedGoogle Scholar
  57. 57.
    Love RP, Newcomb PA, Weibe DA, Surawicz TS, Jordan VC, Carbone PP, DeMets DL: Effects of Tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. J Natl Cancer Inst 82: 1327–1332, 1990PubMedGoogle Scholar
  58. 58.
    Makita M, Sakamoto G,et al.: Natural history of breast cancer among Japanese and Caucasian females. Gan To Kagaku Ryoho 17: 7: 1239–1243, 1990PubMedGoogle Scholar
  59. 59.
    Meydani SN: Dietary modulation of cytokine production and biologic functions. Nutr Rev 48: 361–367, 1990PubMedGoogle Scholar
  60. 60.
    Morrison AS, Lowe CR, MacMahon B,et al.: Some international differences in treatment and survival in breast cancer. Int J Cancer 18: 269–273, 1976PubMedGoogle Scholar
  61. 61.
    Moscat J, Molloy CJ, Fleming TP,et al.: Epidermal growth factor activates phosphoinositide turnover and protein kinase C in BALB/MK keratinocytes. Mol Endocrinol 2: 799–805, 1988PubMedGoogle Scholar
  62. 62.
    Muldoon MF, Manuck SB, Matthews KA: Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. Br Med J 301: 309–14, 1990Google Scholar
  63. 63.
    Newman SC, Miller AB, Howe GR: A study of the effect of weight and dietary fat on breast cancer survival time. Am J Epidemiol 123: 767–773, 1986PubMedGoogle Scholar
  64. 64.
    Norton L: A Gompertzian model of human breast cancer growth. Cancer Res 48: 7067–6101, 1988PubMedGoogle Scholar
  65. 65.
    Powles TJ, Tillyer CR, Jones AL, Ashley SE, Treleavan J, Davey JB, McKinnis JA: Prevention of breast cancer with Tamoxifen — an update on the Royal Marsden Hospital Pilot Programme. Eur J Cancer 26: 680–684, 1990PubMedGoogle Scholar
  66. 66.
    Prentice RL, Kakar R, Husting S,et al.: Aspects of the rationale for the Women's Health Trial. J Natl Cancer Inst 80: 802–814, 1988PubMedGoogle Scholar
  67. 67.
    Prentice RL: Dietary fat reduction and estradiol concentration in healthy post-menopausal women. J Natl Cancer Inst 82: 129–134, 1990PubMedGoogle Scholar
  68. 68.
    Prentice RL, Pepe M, Self SG: Dietary fat and breast cancer: a quantitative assessment of the epidemiological literature and a discussion of methodological issues. Cancer Res 49: 3147–3156, 1989PubMedGoogle Scholar
  69. 69.
    Prior R, Waterhouse JAH: The incidence of bilateral breast cancer: II. A proposed model for the analysis of coincidental tumors. Br J Cancer 43: 615–622, 1981PubMedGoogle Scholar
  70. 70.
    Rose DP, Boyar AP, Wynder EL: International comparison of mortality rates for cancer of the breast, ovary, prostrate, and colon, and per capita food consumption. Cancer 58: 2363–2371, 1986PubMedGoogle Scholar
  71. 71.
    Rose DP, Boyar AP, Cohen C,et al.: Effect of a low-fat diet on hormone levels in women with cystic breast disease. I. Serum steroids and gonadotropins. J Natl Cancer Inst 78: 623–626, 1987PubMedGoogle Scholar
  72. 72.
    Rose DP, Connolly JM: Stimulation of growth of human breast cancer cell lines in culture by linoleic acid. Biochem Biophys Res Commun 164: 277–283, 1989PubMedGoogle Scholar
  73. 73.
    Rose DP, Connolly JM: Effects of fatty acids and inhibitors of eicosanoid synthesis on the growth of a human breast cancer cell line in culture. Cancer Res 50: 7139–7144, 1990Google Scholar
  74. 74.
    Sakamoto G, Sugano H, Hartman WH: Stage-by-stage survival from breast cancer in the U.S. and Japan. Jap J Cancer 25: 161–170, 1979Google Scholar
  75. 75.
    Schell SR, Montague ED, Spanos WJ Jr,et al.: Bilateral breast cancer in patients with initial stage I and II disease. Cancer 50: 1191–1194, 1982PubMedGoogle Scholar
  76. 76.
    Schimizer H, Ross RK, Bernstein L, Pike MC, Henderson BE: Serum estrogen levels in postmenopausal women; comparison of American whites and Japanese in Japan. Brit J Cancer 62: 451–455, 1990PubMedGoogle Scholar
  77. 77.
    Scholar EM, Louis AD, Newland J,et al.: The effect of dietary fat on metastasis of the Lewis lung carcinoma and the BALB/c mammary carcinoma. Nutr Cancer 12: 109–119, 1989PubMedGoogle Scholar
  78. 78.
    Senie RT, Rosen PP: The relationship of obesity to breast cancer early detection behaviour; stage at diagnosis; and disease-free survival at 10 years. Prev Med 19: 583, 1990Google Scholar
  79. 79.
    Silverman J, Powers J, Stromberg P,et al.: Effects on C3H mouse mammary cancer of changing from a high fat to a low fat diet before, at, or after puberty. Cancer Res 49: 3857–3860, 1989PubMedGoogle Scholar
  80. 80.
    Tannenbaum A: The genesis and growth of tumors. III. Effect of a high fat diet. Cancer Res 2: 468–475, 1942Google Scholar
  81. 81.
    Telang NT, Basu A, Kurihara H, Osborne MP, Modatz MJ: Modulation in the expression of murine mammary tumor virus, ras proto-oncogenes, and alveolar hyperplasia by fatty acids in mouse mammary explant cultures. Anticancer Res 8: 971–976, 1988PubMedGoogle Scholar
  82. 82.
    Thomas IK, Erickson KL: Lipid modulation of mammary tumor cell cytolysis: Direct influence of dietary fats on the effector component of cell-mediated cytotoxicity. J Natl Cancer Inst 74: 675–680, 1985PubMedGoogle Scholar
  83. 83.
    Tretli S, Haldorsen T, Ottestad L: The effect of pre-morbid height and weight on the survival of breast cancer patients. Brit J Cancer 62: 299–304, 1990PubMedGoogle Scholar
  84. 84.
    Verreault R, Brisson J, Deschene I,et al.: Dietary fat in relation to prognostic indicators in breast cancer patients. J Natl Cancer Inst 80: 819–825, 1988PubMedGoogle Scholar
  85. 85.
    Welsch CW, House JL, Herr BL, Eliasberg SJ, Welsch MA: Enhancement of mammary carcinogenesis of high levels of dietary fat: a phenomenon dependent on ad libitum feeding. J Natl Cancer Inst 82: 1615–1620, 1990PubMedGoogle Scholar
  86. 86.
    Willet WC, Stampfer MJ, Colditz GA,et al.: Dietary fat and the risk of breast cancer. N Engl J Med 316: 1–7, 1987PubMedGoogle Scholar
  87. 87.
    Wynder EL, Cohen LA: A rationale for dietary intervention in the treatment of postmenopausal breast cancer patients. Nutr Cancer 3: 195–200, 1982PubMedGoogle Scholar
  88. 88.
    Wynder EL, Kajitani T, Kuno J, Lucas JC,et al.: A comparison of survival rates between American and Japanese patients with breast cancer. Gynec Obstet 111: 196–200, 1963Google Scholar
  89. 89.
    Wynder EL, Rose DP, Cohen LA: Diet and breast cancer in causation and therapy. Cancer 58: 1804–1815, 1986PubMedGoogle Scholar
  90. 90.
    Yonemoto RH: Breast cancer in Japan and the United States. Epidemiology, hormone receptors, pathology, and survival. Arch Surg 115: 1056–1062, 1980PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1991

Authors and Affiliations

  • Rowan T. Chlebowski
    • 1
  • David Rose
    • 2
  • I. Marilyn Buzzard
    • 3
  • George L. Blackburn
    • 4
  • William InsullJr.
    • 5
  • Mary Grosvenor
    • 1
  • Robert Elashoff
    • 6
  • Ernst L. Wynder
    • 2
  • For the Women's Intervention Nutrition Study (WINS)
  1. 1.UCLA School of MedicineHarbor-UCLA Medical Center, Division of Medical OncologyTorranceUSA
  2. 2.American Health FoundationNew York
  3. 3.University of MinnesotaMinneapolis
  4. 4.Harvard Medical SchoolNew England Deaconess HospitalBoston
  5. 5.Methodist Hospital Lipid Research CenterHouston
  6. 6.UCLA School of Public HealthLos AngelesUSA

Personalised recommendations