Skip to main content
SpringerLink
Log in

The Role of Endogenous Hormones in the Etiology and Prevention of Breast Cancer: The Epidemiological Evidence

  • Conference paper
Tumor Prevention and Genetics III

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 166))

Abstract

Breast cancer is the most common cause of cancer death in women worldwide. Rates vary about fivefold around the world, but they are increasing in regions that until recently had low rates of disease. Despite the numerous uncertainties surrounding the etiology of breast cancer, intensive epidemiological, clinical, and genetic studies have identified a number of biological and social traits as risk factors associated with breast cancer. Principal among them is the evidence of BRCA1 and BRCA2 susceptibility genes, familial history of breast cancer, age, higher socioeconomic status, ionizing radiation, tallness in adult life, alcohol consumption, and a variety of hormone and metabolic factors. Among the hormonal influences, a relevant etiological function has been ascribed to unopposed exposure to elevated levels of estrogens and androgens. In addition, new epidemiologic evidence has indicated that among the metabolic factors, glucose metabolism, hyperinsulinemic insulin resistance, and insulin-like growth factor bioavailability may also play a role in breast cancer. These endocrine and metabolic factors may represent future targets for breast cancer prevention.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. International Agency for Research on Cancer (1987) Overall evaluations of carcinogenicity: an updating of IARC monograph volumes 1 to 42. IARC monograph on the evaluation of carcinogenic risk to humans. Suppl 7. Lyon, pp 272–310

    Google Scholar 

  2. Landis SH, Murray T, Bolden S, Wingo PA (1999) Cancer statistics, 1999. CA Cancer J Clin 49:8–31

    PubMed  CAS  Google Scholar 

  3. Mettlin C (1999) Global breast cancer mortality statistics, 1999. CA Cancer J Clin 49:138–144

    Article  PubMed  CAS  Google Scholar 

  4. Bernstein L, Ross RK (1993) Endogenous hormones and breast cancer risk. Epidemiol Rev 15:48–65

    PubMed  CAS  Google Scholar 

  5. Russo J, Hu YF, Yang X, Russo IH (2000) Developmental, cellular, and molecular basis of human breast cancer. J Natl Cancer Inst Monogr 27:17–37

    PubMed  CAS  Google Scholar 

  6. Secreto G, Recchione C, Fariselli G, Di Pietro S (1984) High testosterone and low progesterone circulating levels in premenopausal patients with hyperplasia and cancer of the breast. Cancer Res 44:841–844

    PubMed  CAS  Google Scholar 

  7. Secreto G, Toniolo P, Pisani P, Recchione C, Cavalleri A, Fariselli G, Totis A, Di Pietro S, Berrino F (1989) Androgens and breast cancer in premenopausal women. Cancer Res 49:471–476

    PubMed  CAS  Google Scholar 

  8. Beatson GT (1896) On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment with illustrative cases. Lancet 2:104–207

    Google Scholar 

  9. Lacassagne A (1932) Apparition de cancers de la mamelle chez la souris male, soumise à des injections de folliculine. CR Acad Sci 195:630–632

    Google Scholar 

  10. Parlin DM, Whelan J, Ferlay L, Raymond L, Young J (eds) (1997) Cancer incidence in five continents, vol. VII. International Agency for Research on Cancer Scientific Publications, Lyon

    Google Scholar 

  11. Cavalieri E, Frenkel K, Liehr JG, Rogan, Roy D (2000) Estrogens as endogenous genotoxic agents-DNA adducts and mutation. J Natl Cancer Inst Monogr 27:75–94

    PubMed  CAS  Google Scholar 

  12. Flölotto T, Djahansouzi S, Gläser M, Hanstein B, Niederacher D, Brumm C, Beckmann MW (2001) Hormones and hormones antagonists: mechanism of action in carcinogenesis of endometrial and breast cancer. Horm Metab Res 33:451–457

    Google Scholar 

  13. Dorgan JF, Longcope C, Stephenson HE Jr, Falk RT, Miller R, Franz C, et al (1996) Relation of prediagnostic serum estrogen and androgen levels to breast cancer risk. Cancer Epidemiol Biomarkers Prev 5:533–539

    PubMed  CAS  Google Scholar 

  14. Dorgan JF, Stanczyk FZ, Longcope C, Stephenson HE Jr, Chang L, Miller R, et al (1997) Relationship of serum dehydroepiandrosterone (DHEA), DHEA sulfate, and 5-androstene-3β,17β-diol to risk of breast cancer in postmenopausal women. Cancer Epidemiol Biomarkers Prev 6:177–181

    PubMed  CAS  Google Scholar 

  15. Thomas HV, Key TJ, Allen DS, Moore JW, Dowsett M, Fentiman IS, et al (1997) A prospective study of endogenous serum hormone concentrations and breast cancer risk in postmenopausal women on the island of Guernsey. Br J Cancer 76:401–405

    PubMed  CAS  Google Scholar 

  16. Hankinson SE, Willett WC, Manson JE, Colditz GA, Hunter DJ, Spiegelman D, et al (1998) Plasma sex steroid hormone levels and risk of breast cancer in post menopausal women. J Natl Cancer Inst 90:1292–1299

    Article  PubMed  CAS  Google Scholar 

  17. Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, Banerjee S, Koenig KL, Shore RE, et al (1995) A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Cancer Inst 87:190–197

    PubMed  CAS  Google Scholar 

  18. Zeleniuch-Jacquotte A, Bruning PF, Bonfrer JMG, Koenig KL, Shore RE, Kim MY, et al (1997) Relation of serum levels of testosterone and dehydroepiandrosterone sulfate to risk of breast cancer in postmenopausal women. Am J Epidemiol 145:1030–1038

    PubMed  CAS  Google Scholar 

  19. Berrino F, Muti P, Micheli A, Bolelli G, Krogh V, Sciajno R, et al (1996) Serum sex hormone levels after menopause and subsequent breast cancer. J Natl Cancer Inst 88:291–296

    PubMed  CAS  Google Scholar 

  20. Barrett-Connor E, Friedlander NJ, Khaw K-T (1990) Dehydroepiandrosterone sulfate and breast cancer risk. Cancer Res 50:6571–6574

    PubMed  CAS  Google Scholar 

  21. Garland CF, Friedlander NJ, Barrett-Connor E, Khaw K-T (1992) Sex hormones and postmenopausal breast cancer: a prospective study in an adult community. Am J Epidemiol 135:1220–1230

    PubMed  CAS  Google Scholar 

  22. Kabuto M, Akiba S, Stevens RG, Neriishi K, Land CE (2000) A prospective study of estradiol and breast cancer in Japanese women. Cancer Epidemiol Biomarkers Prev 9:575–579

    PubMed  CAS  Google Scholar 

  23. Cauley JA, Lucas FL, Kuller LH, Stone K, Browner W, Cummings SR, for the Study of Osteoporotic Fractures Research Group (1999) Elevated serum estradiol and testosterone concentrations are associated with a high risk for breast cancer. Ann Intern Med 130:270–277

    PubMed  CAS  Google Scholar 

  24. Gordon GB, Bush TL, Helzlsouer KJ, Miller SR, Comstock GW (1990) Relationship of serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing postmenopausal breast cancer. Cancer Res 50:3859–3862

    PubMed  CAS  Google Scholar 

  25. Helzlsouer KJ, Alberg AJ, Bush TL, Longcope C, Gordon GB, Comstock GW (1994) A prospective study of endogenous hormones and breast cancer. Cancer Detect Prev 18:79–85

    PubMed  CAS  Google Scholar 

  26. Endogenous Hormones and Breast Cancer Collaborative Group (2002) Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94:606–616

    Google Scholar 

  27. James VH, McNeill JM, Lai LC, Newton CJ, Ghilchik MW, Reed MJ (1987) Aromatase activity in normal breast and breast tumor tissues: in vivo and in vitro studies. Steroids 50:269–279

    Article  PubMed  CAS  Google Scholar 

  28. Berrino F, Muti P (1988) Overview of the etiological hypotheses linking endogenous steroid hormones and breast cancer. In: Riboli E, Saracci R (eds) Diet, hormones and cancer: methodological issues for prospective studies. IARC Technical Report No. 4, Lyon

    Google Scholar 

  29. Wysowski DK, Comstock GW, Helsing KJ, Lau HL (1987) Sex hormone levels in serum in relation to the development of breast cancer. Am J Epidemiol 125:791–799

    PubMed  CAS  Google Scholar 

  30. Rosenberg CR, Pasternack BS, Shore RE, Koenig KL, Toniolo PG (1994) Premenopausal estradiol levels and the risks of breast cancer: a new method of controlling for day of the menstrual cycle. Am J Epidemiol 140:518–525

    PubMed  CAS  Google Scholar 

  31. Key TJA, Wang DY, Brown JB, Hermon C, Allen DS, Moore JW, Bulbrook RD, Fentiman IS, Pike MC (1996) A prospective study of urinary oestrogen excretion and breast cancer risk. Br J Cancer 73:1615–1619

    PubMed  CAS  Google Scholar 

  32. Thomas HV, Key TJ, Moore JW, Dowsett M, Fentiman IS, Wang DY (1997) A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey. Br J Cancer 75:1075–1079

    PubMed  CAS  Google Scholar 

  33. Kelsey JL, Gammon MD, John EM (1993) Reproductive factors and breast cancer. Epidemiol Rev 15:36–47

    PubMed  CAS  Google Scholar 

  34. Catt KJ, Dufau ML (1991) Gonadotropic hormones: byosinthesis secretion, receptors, and action. In: Yes SS, Jaffe RB (eds) Reproductive endocrinology. Sauders and Company, Philadelphia, pp 105–155

    Google Scholar 

  35. Milazzo G, Giorgino F, Damante F, et al (1992) Insulin receptor expression and function in human breast cancer cell lines. Cancer Res 52:3924–3930

    PubMed  CAS  Google Scholar 

  36. Cullen KJ, Yee D, Sly WS, Perdue J, Hampton B, Lippman ME, Rosen N (1990) Insulin like growth factor receptor expression and function in human breast cancer. Cancer Res 50:48–53

    PubMed  CAS  Google Scholar 

  37. Osborne CK, Clemmons DR, Arteaga CI (1990) Regulation of breast cancer growth by insulin-like growth factors. J Steroid Biochem Mol Biol 37:805–809

    PubMed  CAS  Google Scholar 

  38. Cara JF (1994) Insulin-like growth factors, insulin-like growth factor binding proteins and ovarian androgen production. Horm Res 42:49–54

    Article  PubMed  CAS  Google Scholar 

  39. Barbieri RL, Makris A, Ryan KJ (1984) Insulin stimulates androgen accumulation in incubations of human ovarian stroma and theca. Obstet Gynecol 64:73S–80S

    PubMed  CAS  Google Scholar 

  40. Nestler JE, Jakubowicz DJ (1996) Decreases in ovarian cytochrome P450c17 alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome [see comments]. N Engl J Med 335:617–623

    Article  PubMed  CAS  Google Scholar 

  41. Lewitt MS (1994) Role of the insulin-like growth factors in the endocrine control of glucose homeostasis. Diabetes Res Clin Pract 23:3–15

    Article  PubMed  CAS  Google Scholar 

  42. Jones JI, Clemmons DR (1995) Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev 16:3–34

    Article  PubMed  CAS  Google Scholar 

  43. Rinderknecht E, Humbel RE (1978) Primary structure of human insulin-like growth factor II. FEBS Lett 89:283–286

    Article  PubMed  CAS  Google Scholar 

  44. Salter J, Best CH (1953) Insulin as a growth hormone. Br Med J (Aug 15):353–358

    Google Scholar 

  45. Zapf J (1997) The IGF-insulin relationship. J Pediatr Endocrinol Metabol 10:87–95

    Google Scholar 

  46. Clemmons DR, Underwood LE (1991) Nutritional regulation of IGF-I and IGF binding proteins. Annu Rev Nutr 11:393–412

    Article  PubMed  CAS  Google Scholar 

  47. Werner H, LeRoith D (1996) The role of the insulin-like growth factor system in human cancer. Adv Cancer Res 68:183–223

    PubMed  CAS  Google Scholar 

  48. Stewart CE, Rotwein P (1996) Growth, differentiation, and survival: multiple physiological functions for insulin-like growth factors. Physiol Rev 76:1005–1026

    PubMed  CAS  Google Scholar 

  49. Dickson RB, Lippman ME (1995) Growth factors in breast cancer. Endocr Rev 16:559–589

    Article  PubMed  CAS  Google Scholar 

  50. Baserga R (1995) The insulin-like growth factor I receptor: a key to tumor growth? Cancer Res 55:249–252

    PubMed  CAS  Google Scholar 

  51. Berns EM, Klijn JG, van SI, Portengen H, Foekens JA (1992) Sporadic amplification of the insulin-like growth factor 1 receptor gene in human breast tumors. Cancer Res 52:1036–1039

    PubMed  CAS  Google Scholar 

  52. Thissen JP, Ketelslegers JM, Underwood LE (1994) Nutritional regulation of the insulin-like growth factors. Endocr Rev 15:80–101

    Article  PubMed  CAS  Google Scholar 

  53. Baxter RC, Turtle JR (1978) Regulation of hepatic growth hormone receptors by insulin. Biochem Biophys Res Commun 84:350–357

    Article  PubMed  CAS  Google Scholar 

  54. Plymate SR, Jones RE, Matej LA, Friedl KE (1988) Regulation of sex hormone binding globulin (SHBG) production in Hep G2 cells by insulin. Steroids 52:339–340

    Article  PubMed  CAS  Google Scholar 

  55. Crave JC, Lejeune H, Brebant C, Baret C, Pugeat M (1995) Differential effects of insulin and insulin-like growth factor I on the production of plasma steroid-binding globulins by human hepatoblastoma-derived (Hep G2) cells. J Clin Endocrinol Metab 80:1283–1289

    PubMed  CAS  Google Scholar 

  56. Stein P, Bussmann LE, Tesone M (1995) In vivo regulation of the steroidogenic activity of rat luteal cells by insulin. J Steroid Biochem Mol Biol 52:329–335

    Article  PubMed  CAS  Google Scholar 

  57. Hankinson SE, Willett WC, Colditz GA, et al (1998) Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet 351:1393–1396

    Article  PubMed  CAS  Google Scholar 

  58. Toniolo P, Bruning PF, Akhmedkhanov A, Bonfrer JM, Koenig KL, Lukanova A, Shore RE, Zeleniuch-Jacquotte A (2000) Serum insulin-like growth factor-I and breast cancer. Int J Cancer 88:828–832

    Article  PubMed  CAS  Google Scholar 

  59. Muti P, Quattrin T, Grant B, Krogh V, Micheli A, Ram M, Freudenheim JL, Schünemann HJ, Sieri, S, Trevisan M, Berrino F (2002) Fasting glucose, insulin and insulin-like growth factor (IGF)-I pattern in relation to breast cancer risk: a prospective Study. Cancer Epidemiol Biomarkers Prev 11:1361–1368

    PubMed  CAS  Google Scholar 

  60. Krajcik RA, Borofsky ND, Massardo S, Orentreich N (2002) Insulin-like growth factor I (IGF), IGF-binding proteins, and breast cancer. Cancer Epidemiol Biomarkers Prev 11:1566–1573

    PubMed  CAS  Google Scholar 

  61. Jernström H, Deal C, Wilkin F, Chu W, Tao Y, Majeed N, Hudson T, Narod SA, Pollak M (2001) Genetic and nongenetic factors associated with variation of plasma levels of insulin-like growth factor-I and insulin-like growth factor-binding protein-3 in healthy premenopausal women. Cancer Epidemiol Biomarkers Prev 10(4):377–384

    PubMed  Google Scholar 

  62. Warburg O (1956) On the origin of cancer cells. Science 123:309–314

    PubMed  CAS  Google Scholar 

  63. Franco Berrino, Cristina Bellati, Giorgio Secreto, Edgarda Camerini, Valeria Pala, Salvatore Panico, Giovanni Allegro, Rudolf Kaaks (2001) Reducing bioavailable sex hormones through a comprehensive change in diet: the Diet and Androgens (DIANA) randomized trial. Cancer Epidemiol Biomarkers Prev 10:25–33

    PubMed  CAS  Google Scholar 

  64. Rose DP, Connolly JM, Chlebowski RT, Buzzard IM, Wynder EL (1993) 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. Breast Cancer Res Treat 27:253–262

    Article  PubMed  CAS  Google Scholar 

  65. Schaefer EJ, Lichtenstein AH, Lamon-Fava S, McNamara JR, Schaefer MM, Rasmussen H, Ordovas JM (1995) Body weight and low-density lipoprotein cholesterol changes after consumption of a low-fat ad libitum diet. J Am Med Assoc 274:1450–1455

    Article  CAS  Google Scholar 

  66. Shah M, McGovern P, French S, Baxter J (1994) Comparison of a low-fat, ad libitum complex-carbohydrate diet with a low-energy diet in moderately obese women. Am J Clin Nutr 59:980–984

    PubMed  CAS  Google Scholar 

  67. Grenman S, Ronnemaa T, Irjala K, Kaihola HL, Gronroos M (1986) Sex steroid, gonadotropin, cortisol, and prolactin levels in healthy, massively obese women: correlation with abdominal fat cell size and effect of weight reduction. J Clin Endocrinol Metab 63:1257–1261

    Article  PubMed  CAS  Google Scholar 

  68. Svendsen OL, Hassager C, Christiansen C (1995) The response to treatment of overweight in postmenopausal women is not related to fat distribution. Int J Obes Relat Metab Disord 19:496–502

    PubMed  CAS  Google Scholar 

  69. Kiddy, DS, Hamilton-Fairley, D, Seppala, M, Koistinen, R, James, VH, Reed, MJ, and Franks, S (1989) Diet-induced changes in sex hormone binding globulin and free testosterone in women with normal or polycystic ovaries: correlation with serum insulin and insulin-like growth factor-I. Clin Endocrinol (Oxf) 31:757–763

    CAS  Google Scholar 

  70. Guzick DS, Wing R, Smith D, Berga SL, Winters SJ (1994) Endocrine consequences of weight loss in obese, hyperandrogenic, anovulatory women. Fertil Steril 61:598–604

    PubMed  CAS  Google Scholar 

  71. Crave JC, Fimbel S, Lejeune H, Cugnardey N, Dechaud H, Pugeat M (1995) Effects of diet and metformin administration on sex hormone-binding globulin, androgens, and insulin in hirsute and obese women. J Clin Endocrinol Metab 80:2057–2062

    PubMed  CAS  Google Scholar 

  72. O’Dea JP, Wieland RG, Hallberg MC, Llerena LA, Zorn EM, Genuth SM (1979) Effect of dietary weight loss on sex steroid binding sex steroids, and gonadotropins in obese postmenopausal women. J Lab Clin Med 93:1004–1008

    PubMed  CAS  Google Scholar 

  73. Bates GW, Whitworth NS (1982) Effect of body weight reduction on plasma androgens in obese, infertile women. Fertil Steril 38:406–409

    PubMed  CAS  Google Scholar 

  74. Ingram DM, Bennett FC, Willcox D, de Klerk N (1987) Effect of low-fat diet on female sex hormone levels. J Natl Cancer Inst 79:1225–1229

    PubMed  CAS  Google Scholar 

  75. Prentice R, Thompson D, Clifford C, Gorbach S, Goldin B, Byar D (1990) Dietary fat reduction and plasma estradiol concentration in healthy postmenopausal women. The Women’s Health Trial Study Group. J Natl Cancer Inst 82:129–134

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Social and Preventive Medicine, University at Buffalo, State University of New York, 270 Farber Hall, 3435 Main Street, Buffalo, NY, 14214, USA

    Paola Muti

Authors
  1. Paola Muti
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Zentrum für Tumordiagnostik und Prävention, Rorschacherstrasse 150, 9006, St. Gallen, Switzerland

    Hans-Jörg Senn  & Rudolf Morant  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Muti, P. (2005). The Role of Endogenous Hormones in the Etiology and Prevention of Breast Cancer: The Epidemiological Evidence. In: Senn, HJ., Morant, R. (eds) Tumor Prevention and Genetics III. Recent Results in Cancer Research, vol 166. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26980-0_16

Download citation

  • DOI: https://doi.org/10.1007/3-540-26980-0_16

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-22228-6

  • Online ISBN: 978-3-540-26980-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation