Breast Cancer Research and Treatment

, Volume 27, Issue 3, pp 253–262 | Cite as

The effects of a low-fat dietary intervention and tamoxifen adjuvant therapy on the serum estrogen and sex hormone-binding globulin concentrations of postmenopausal breast cancer patients

  • David P. Rose
  • Jeanne M. Connolly
  • Rowan T. Chlebowski
  • I. Marilyn Buzzard
  • Ernst L. Wynder


The purpose of the study was to determine the effect of a low-fat dietary intervention, with or without concomitant tamoxifen adjuvant therapy, on serum estrogen and sex hormone-binding globulin (SHBG) levels in postmenopausal patients with resected breast cancer. Ninety-three patients were randomized to either reduce their fat intake to 15–20% of total calories, or to a dietary control group. Serum estradiol, estrone, estrone sulfate, and SHBG concentrations were assayed at baseline, and at 6, 12, and 18 months thereafter. In 19% of patients, the preintervention serum estradiol levels were below the sensitivity of the assay (5 pg/ml). Tamoxifen had no significant effect on serum estrogen levels, but produced an elevation in SHBG. Patients with reliably quantifiable preintervention estradiol concentrations (≥ 10 pg/ml) showed a significant reduction in serum estradiol after 6 months on the low-fat diet (average, 20%; p < 0.005); this was sustained over the 18 month study period. Serum SHBG levels were increased by tamoxifen therapy, but were reduced significantly (p = 0.01) after 12 months on the low-fat diet in patients not receiving tamoxifen. No changes in serum estrone or estrone sulfate resulted from the dietary intervention. While the low-fat diet produced significant weight loss, patients treated with tamoxifen without dietary intervention showed a gain in body weight. These weight changes produced disruptions in the normal positive correlation between body weight and serum estrone sulfate, and the negative correlation with SHBG concentration.

Key words

dietary fat breast cancer estrogens 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Wynder EL, Rose DP, Cohen LA: Diet and breast cancer in causation and therapy. Cancer 58: 1804–1813, 1986Google Scholar
  2. 2.
    Rose DP: Dietary factors and breast cancer. Cancer Surveys 5: 671–687, 1986Google Scholar
  3. 3.
    Prentice RL, Sheppard L: Dietary fat and cancer: consistency of the epidemiologic data, and disease prevention that may follow from a practical reduction in fat consumption. Cancer Cause Control 1: 81–97, 1990Google Scholar
  4. 4.
    Chlebowski RT, Rose DP, Buzzard IM, Blackburn GL, Insull W Jr, Grosvenor M, Elashoff R, Wynder EL: Adjuvant dietary fat intake reduction in postmenopausal breast cancer patient management. Breast Cancer Res Treat 20: 73–84, 1992Google Scholar
  5. 5.
    Willett WC, Hunter DJ, Stampfer MJ, Colditz G, Manson JE, Spiegelman D, Rosner B, Hennekens CH, Speizer FE: Dietary fat and fiber in relation to risk of breast cancer. J Am Med Assoc 268: 2037–2044, 1992Google Scholar
  6. 6.
    Holm L-E, Nordevang E, Hjalmar M-L, Lidbrink E, Callmer E, Nilsson B: Treatment failure and dietary habits in women with breast cancer. JNCI 85: 32–36, 1993Google Scholar
  7. 7.
    Rose DP, Boyar AP, Cohen C, Strong LE: Effect of a low-fat diet on hormone levels in women with cystic breast disease. I. Serum steroids and gonadotropins. JNCI 78: 623–626, 1987Google Scholar
  8. 8.
    Prentice R, Thompson D, Clifford C, Gorbach S, Goldin B, Byar D: Dietary fat reduction and plasma estradiol concentration in healthy postmenopausal women. JNCI 82: 129–134, 1990Google Scholar
  9. 9.
    Heber D, Ashley JM, Leaf DA, Barnard RJ: Reduction of serum estradiol in postmenopausal women given free access to low-fat high carbohydrate diet. Nutrition 7: 137–141, 1991Google Scholar
  10. 10.
    Boyar AP, Rose DP, Loughridge JR, Engle A, Palgi A, Laakso K, Kinne D, Wynder EL: Response to a diet low in total fat in women with postmenopausal breast cancer: a pilot study. Nutr Cancer 11: 93–99, 1988Google Scholar
  11. 11.
    Longcope C: Hormone dynamics at the menopause. Ann NY Acad Sci 592: 21–30, 1990Google Scholar
  12. 12.
    Chlebowski RT, Rose DP, Buzzard IM, Blackburn GL, York M, Insull W Jr, Khandekar J, Martino S, Elashoff RM, Wynder EL: Dietary fat reduction in adjuvant breast cancer therapy: current rationale and feasibility issues. Adjuvant Ther Cancer 6: 357–363, 1990Google Scholar
  13. 13.
    Buzzard IM, Asp EH, Chlebowski RT, Boyar AP, Jeffery RW, Nixon DW, Blackburn GL, Jochimsen PR, Scanlon EF, Insull W Jr, Elashoff RM, Butrum R, Wynder EL: Diet intervention methods reduce fat intake: Nutrient and food group composition of self-selected low-fat diets. J Am Diet Assoc 90: 42–50, 53, 1990Google Scholar
  14. 14.
    Shimizu H, Ross RK, Bernstein L, Pike MC, Henderson BE: Serum oestrogen levels in postmenopausal women: comparison of American whites and Japanese in Japan. Br J Cancer 62: 451–453, 1990Google Scholar
  15. 15.
    Wynder EL, Fujita Y, Harris RE, Hirayama T, Hiyama T: Comparative epidemiology of cancer between the United States and Japan. Cancer 67: 746–763, 1991Google Scholar
  16. 16.
    Vermeulen A: The hormonal activity of the post-menopausal ovary. J Clin Endocrinol Metab 42: 247–253, 1976Google Scholar
  17. 17.
    Deslypere JP, Verdonck L, Vermeulen A: Fat tissue: a steroid reservoir and site of steroid metabolism. J Clin Endocrinol Metab 61: 564–570, 1985Google Scholar
  18. 18.
    Wang DY, Key TJA, Pike MC, Boreham J, Chen J: Serum hormone levels in British and rural Chinese females. Breast Cancer Res Treat 18: S41-S45, 1991Google Scholar
  19. 19.
    Beranek PA, Folkerd EJ, Ghilchik MW, James VHT: 17β-hydroxysteroid dehydrogenase and aromatase activity in breast fat from women with benign and malignant breast tumors. Clin Endocrinol 20: 205–212, 1984Google Scholar
  20. 20.
    Prost N, Turrel MO, Dahan N, Craveur C, Adessi GL: Estrone and dehydroepiandrosterone sulfatase activities and plasma estrone sulfate levels in human breast carcinoma. Cancer Res 44: 661–664, 1984Google Scholar
  21. 21.
    Noel CT, Reed MJ, Jacobs HS, James VHT: The plasma concentration of oestrone sulfate in postmenopausal women: lack of diurnal variation, effect of ovariectomy, age and weight. J Steroid Biochem 14: 1101–1105, 1981Google Scholar
  22. 22.
    Jasonni VM, Bulletti C, Franceschetti F, Bonavia M, Bolelli G, Ciotti P, Flamigni CL: Estrone sulphate plasma levels in postmenopausal women with and without endometrial cancer. Cancer 53: 2698–2700, 1984Google Scholar
  23. 23.
    Rose DP: Dietary factors and breast cancer. Cancer Surv 5: 671–687, 1986Google Scholar
  24. 24.
    Jordan VC, Fritz NF, Tormey DC: Endocrine effects of adjuvant chemotherapy and long-term tamoxifen administration on node-positive patients with breast cancer. Cancer Res 47: 624–630, 1987Google Scholar
  25. 25.
    Cuzick J, Allen D, Baum M, Barrett J, Clark G, Kakkar V, Melissari E, Moniz C, Moore J, Parsons V, Pemberton K, Pitt P, Richmond W, Houghton J, Riley D: Long term effects of tamoxifen. Eur J Cancer 29A: 15–21, 1993Google Scholar
  26. 26.
    Rose DP, Chlebowski RT, Connolly JM, Jones LA, Wynder EL: The effects of tamoxifen adjuvant therapy and a low-fat diet on serum binding proteins and estradiol bioavailability in postmenopausal breast cancer patients. Cancer Res 52: 5386–5390, 1992Google Scholar
  27. 27.
    Dixon J, Moritz DA, Baker FL: Breast cancer and weight gain: An unexpected finding. Oncol Nurs Forum 5: 5–7, 1978Google Scholar
  28. 28.
    Heasman KZ, Sutherland JH, Campbell JA, Elhakim T, Boyd NF: Weight gain during adjuvant chemotherapy for breast cancer. Breast Cancer Res Treat 5: 195–200, 1986Google Scholar
  29. 29.
    Camoriano JK, Loprinzi CL, Ingle JN, Therneau TM, Krook JE, Veeder MH: Weight change in women treated with adjuvant therapy or observed following mastectomy for nodepositive breast cancer. J Clin Oncol 8: 1327–1334, 1990Google Scholar
  30. 30.
    Fisher B, Costantino J, Redmond C,et al.: A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogenreceptor-positive tumors. N Engl J Med 320: 479–484, 1989Google Scholar
  31. 31.
    Hoskin PJ, Ashley S, Yarnold JR: Changes in body weight after treatment for breast cancer and the effect of tamoxifen. Br J Cancer 62 (Suppl XI): 26, 1990Google Scholar
  32. 32.
    DeMoor P, Joosens JV: An inverse relation between body weight and the activity of the steroid binding globulin in human plasma. Steroidologia 1: 129–136, 1970Google Scholar
  33. 33.
    Moore JW, Key TJA, Bulbrook RD, Clark GMG, Allen DS, Wang DY, Pike MC: Sex hormone binding globulin and risk factors for breast cancer in a population of normal women who had never used exogenous sex hormones. Br J Cancer 56: 661–666, 1987Google Scholar
  34. 34.
    Rose DP, Connolly JM, Meschter CL: Effect of dietary fat on human breast cancer growth and lung metastasis in nude mice. JNCI 83: 1491–1495, 1991Google Scholar
  35. 35.
    Rose DP, Connolly JM: Influence of dietary fat intake on local recurrence and progression of metastases arising from MDA-MB-435 human breast cancer cells in nude mice after excision of the primary tumor. Nutr Cancer 18: 113–122, 1992Google Scholar

Copyright information

© Kluwer Academic Publishers 1993

Authors and Affiliations

  • David P. Rose
    • 1
  • Jeanne M. Connolly
    • 1
  • Rowan T. Chlebowski
    • 2
  • I. Marilyn Buzzard
    • 3
  • Ernst L. Wynder
    • 1
  1. 1.Division of Nutrition and EndocrinologyAmerican Health FoundationValhallaUSA
  2. 2.Harbor-UCLA Medical CenterTorranceUSA
  3. 3.University of Minnesota School of Public HealthMinneapolisUSA

Personalised recommendations