Skip to main content
SpringerLink
Log in

Aromatase Inhibition and Breast Cancer

  • Chapter
Book cover Hormonal Carcinogenesis IV

  • 609 Accesses

Summary

The latest generation of aromatase inhibitors comprises highly potent and specific endocrine agents. They have a central role in the management of hormone-dependent BC, and their potential as preventative agents in women at high risk of the disease is currently being explored in clinical trials.

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 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 169.99
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. Miller WR (1996) Estrogen and Breast Cancer. R G Landes & Co.

    Google Scholar 

  2. Judd HL, Judd GE, Lucas WE, et al (1974) Endocrine function of the postmenopausal ovary: concentration of androgen and estrogens in ovarian and peripheral vein blood. J Clin Endocrinol Metab 39:1020–1024.

    PubMed  CAS  Google Scholar 

  3. Baird DT, Uno A, Melby JC (1969) Adrenal secretion of androgens and estrogens. J Endocrinol 45:135–136.

    PubMed  CAS  Google Scholar 

  4. Perel E, Killinger DW (1979) The interconversion and aromitization of androgens by human adipose tissue. J Steroid Biochem 10:623–627.

    Article  PubMed  CAS  Google Scholar 

  5. Schweikert HU, Milewich L, Wilson JD (1976) Aromatization of androstenedione by cultured human fibroblasts. J Clin Endocrinol Metab 43:785–795.

    PubMed  CAS  Google Scholar 

  6. Larionov AA, Vasyliev DA, Mason JI, et al (2003) Aromatase in skeletal muscle. J Steroid Biochem & Mol Biol 84:485–492.

    Article  CAS  Google Scholar 

  7. Smuk M, Schwers J (1977) Aromatization of androstenedione by human adult liver in vitro. J Clin Endocrinol Metab 45:1009–1012.

    PubMed  CAS  Google Scholar 

  8. Miller WR, Mullen P, Sourdaine P, et al (1997) Regulation of aromatase activity within the breast. J Steroid Biochem 61:193–202.

    Article  Google Scholar 

  9. Bulun SE, Simpson ER (1994) Regulation of aromatase expression in human tissues. Breast Canc Res Treat 30:19–29.

    Article  CAS  Google Scholar 

  10. Miller WR (1989) Aromatase inhibitors in the treatment of advanced breast cancer. Cancer Treatment Rev 16:83–93.

    Article  CAS  Google Scholar 

  11. Brodie AMH, Brodie HJ, Romanoff L, et al (1982) Inhibition of estrogen biosynthsis and regression of mammary tumors by aromatase inhibitors. Hormonal Cancer Advances Exp Med Biol 138:179–190.

    CAS  Google Scholar 

  12. Lonning PE (2000) Pharmacology and clinical experience with exemestane. Expert Opin Invest Drugs 9:1897–1905.

    Article  CAS  Google Scholar 

  13. Johnston JO, Metcalf BW (1984) Aromatase: a target enzyme in breast cancer. In: Novel Approaches to Cancer Chemotherapy, London: Academic Press, 307–328.

    Google Scholar 

  14. Miller WR, Vidya R, Mullen P, et al (2001) Induction and suppression of aromatase by inhibitors. In: Miller WR, Santen RJ (eds) Aromatase Inhibition and Breast Cancer. New York: Marcel Dekker Inc, 213–225.

    Google Scholar 

  15. Santen RJ, Santner S, Davis B, et al (1978) Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast cancer. J Clin Endocrinol Metab 47:1257–1265.

    PubMed  CAS  Google Scholar 

  16. Plourde PV, Dyroff M, Dukes M (1994) Arimidex: a potent and selective fourth-generation aromatase inhibitor. Breast Canc Res Treatment 30:103–111.

    Article  CAS  Google Scholar 

  17. Iveson TJ, Smith IE, Ahern J, et al (1993) Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in postmenopausal patients with advanced breast cancer. Cancer Res 53:266–270.

    PubMed  CAS  Google Scholar 

  18. Graham-Lorence S, Peterson JA (1996) P450s: structural similarities and functional differences. FASEB J 10:206–214.

    PubMed  CAS  Google Scholar 

  19. Miller WR, Jackson J (2003) The therapeutic potential of aromatase inhibitors. Expert Opin Invest Drugs 12:1–15.

    Article  Google Scholar 

  20. Bhatnagar AS, Miller WR (1999) Pharmacology of inhibitors of estrogen biosynthesis. In: Oettel M, Schillinger E (eds) Handbook of Experimental Pharmacology: Estrogens and Antiestrogens. Berlin: Springer-Verlag, 223–230.

    Google Scholar 

  21. Lonning PE (1996) Pharmacology of new aromatase inhibitors. The Breast 5:202–208.

    Article  Google Scholar 

  22. Geisler J, King N, Anker G, et al (1998) In vivo inhibition of aromatization by exemestane, a novel irreversible aromatase inhibitor, in postmenopausal breast cancer patients. Clin Canc Res 4:2089–2093.

    CAS  Google Scholar 

  23. Miller WR, Dixon JM (2001) Local endocrine effects of aromatase inhibitors within the breast. J Steroid Biochem Mol Biol 79:93–102.

    Article  PubMed  CAS  Google Scholar 

  24. MacNeill FA, Jones AL, Jacobs S, et al (1992) The influence of aminoglutethimide and its analogue rogletimide on peripheral aromatisation in breast cancer. Brit J Cancer 66:692–697.

    PubMed  CAS  Google Scholar 

  25. Jones AL, MacNeill F, Jacobs S, et al (1992) The influence of intramuscular 4-hydroxyandrostenedione on peripheral aromatisation in breast cancer patients. Euro J Cancer 10:1712–1716.

    Article  Google Scholar 

  26. Lonning PE, Jacobs S, Jones A, et al (1991) The influence of CGS 16969A on peripheral aromatisation in breast cancer patients. Brit J Cancer 63:789–793.

    PubMed  CAS  Google Scholar 

  27. Dowsett M, Jones A, Johnston SR, et al (1995) In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer. Clin Canc Res 1:1511–1515.

    CAS  Google Scholar 

  28. Geisler J, King N, Dowsett M, et al (1996) Influence of anastrozole (Arimidex), a selective non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma estrogen levels in postmenopausal women with breast cancer. Brit J Cancer 74:1286–1291.

    PubMed  CAS  Google Scholar 

  29. Thurlimann B, Paridaens R, Serin D, et al (1997) Third-line hormonal treatment with exemestane in postmenopausal patients with advanced breast cancer progressing on aminoglutethimde: a phase II multicentre multinational trial. Euro J Cancer 33:1767–1773.

    Article  CAS  Google Scholar 

  30. Vermeulen A (1986) Human mammary cancers as a site of sex steroid metabolism. Cancer Surveys 5:585–595.

    PubMed  CAS  Google Scholar 

  31. Miller WR (1997) Uptake and synthesis of steroid hormones by the breast. Endocrine Related Cancer 4:307–311.

    CAS  Google Scholar 

  32. Reed AJ, Aherne GW, Ghilchik MW, et al (1991) Concentrations of oestrone and 4-hydroxyandrostenedione in malignant and normal breast tissues. Int J Cancer 49:562–565.

    PubMed  CAS  Google Scholar 

  33. James VHT, Reed MJ, Adams EF, et al (1989) Estrogen uptake and metabolism in vivo. In: Beck JS, editor. Estrogen and the Human Breast. Edinburgh: The Royal Society of Edinburgh, Vol 95B:185–193.

    Google Scholar 

  34. Miller WR, Dixon JM (2001) Local endocrine effects of aromatase inhibitors within the breast. J Steroid Biochem Mol Biol 79:93–102.

    Article  PubMed  CAS  Google Scholar 

  35. Dixon JM (2002) Neoadjuvant therapy: surgical perspectives. In: WR Miller, Ingle JN (eds) Endocrine Therapy in Breast Cancer. New York: Marcel Dekker, 197–212

    Google Scholar 

  36. Dixon JM, Love CDB, Renshaw L, et al (1999) Lessons from the use of aromatase inhibitors in the neoadjuvant setting. Endocrine Related Canc 6:227–230.

    Article  CAS  Google Scholar 

  37. Sasano H, Suzuki T, Moriya T (2002) Pathology of breast cancer following neoadjuvant therapy. In: Miller WR, Ingle JN (eds) Endocrine Therapy in Breast Cancer. New York: Marcel Dekker 213–222.

    Google Scholar 

  38. Miller WR, Dixon JM, Macfarlane L, et al (2002) Pathological features of breast cancer response following neoadjuvant treatment with either letrozole or tamoxifen. Euro J Cancer 39:462–468.

    Article  Google Scholar 

  39. Anderson TJ, Dixon JM, Stuart M, et al (2002) Effect of neoadjuvant treatment with anastrozole on tumour histology in postmenopausal women with large operable breast cancer. Brit J Cancer 87:334–338.

    Article  PubMed  CAS  Google Scholar 

  40. Miller WR, Dixon JM, Cameron DA, et al (2001) Biological and clinical effects of aromatase inhibitors in neoadjuvant therapy. J Steroid Biochem Mol Biol 79:103–107.

    Article  PubMed  CAS  Google Scholar 

  41. Dorgan JF, Longcope C, Stephenson HE Jr, et al (1997) Serum sex hormone levels are related to breast cancer risk in postmenopausal women. Environ HIth Perspect 105(S3):583–585.

    Google Scholar 

  42. Toniolo PG, Levitz M, Zeleniuch-Jacquotte A, et al (1995) A prospective study of endogenous estrogens and breast cancer in postmenopausal women. J Natl Canc Inst 87:190–197.

    CAS  Google Scholar 

  43. Berrino F, Muti P, Micheli A, et al (1996) Serum sex hormone levels after menopause and subsequent breast cancer. J Natl Canc Inst 88:291–296.

    CAS  Google Scholar 

  44. Thomas HV, Key TJ, Allen DS, et al (1997) A prospective study of endogenous serum hormone concentrations and breast cancer risk in premenopausal women on the island of Guernsey. Brit J Cancer 76:401–405.

    PubMed  CAS  Google Scholar 

  45. Thomas HV, Key TJ, Allen DS, et al (1997) A prospective study of endogenous serum hormone concentrations and breast cancer risk in postmenopausal women on the island of Guernsey. Brit J Cancer 75:1075–1079.

    PubMed  CAS  Google Scholar 

  46. Thomas HV, Reeves, GK, Key TJA (1997) Endogenous estrogen and postmenopausal breast cancer: a quantative review. Canc Causes Control 8:922–928.

    Article  CAS  Google Scholar 

  47. Collaborative Group on Hormonal Factors in Breast Cancer (1997) Breast cancer and hormone replacement: Collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Lancet 350:1047–1059

    Article  Google Scholar 

  48. Million Women Study Collaborators. (2003) Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 362:419–427

    Article  CAS  Google Scholar 

  49. Kristensen VN, Andersen TI, Lindblom A, et al (1998) A rare CYP19 (aromatase) variant may increase the risk of breast cancer. Pharmacogenetics 8:43–48.

    PubMed  CAS  Google Scholar 

  50. Haiman CA, Hankinson SE, Speizer FE, et al (1999) A tetranucleotide repeat polymorphism in CYP19 and breast cancer risk. Proc Am Assoc Cancer Res 40:A1290.

    Google Scholar 

  51. O’Neill JS, Miller WR (1987) Aromatase activity in adipose tissue from women with benign and malignant breast disease. Brit J Cancer 56:601–604.

    PubMed  CAS  Google Scholar 

  52. O’Neill JS, Elton RA, Miller WR (1988) Aromatase activity in adipose tissue from breast quadrants: a link with tumour site. Brit Med J 296:741–743.

    Article  CAS  Google Scholar 

  53. Feinleib M (1968) Breast cancer and artificial menopause: a cohort study. J Natl Canc Inst 41:315–329.

    CAS  Google Scholar 

  54. Trichopoulos D, MacMahon B, Cole P (1972) Menopause and breast cancer risk. J Natl Canc Inst 48:605–613.

    CAS  Google Scholar 

  55. Fisher B, Costantino JP, Wickerham DL, et al (1998) Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371–1388.

    Article  PubMed  CAS  Google Scholar 

  56. Early Breast Cancer Trialist’s Collaborative Group (EBCTCG) (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351:1451–1467.

    Article  Google Scholar 

  57. Powles T, Eeles R, Ashley S, et al (1998) Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 352:98–101.

    PubMed  CAS  Google Scholar 

  58. Cummings SR, Eckert S, Krueger KA, et al (1999) The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. JAMA 281:2189–2197.

    Article  PubMed  CAS  Google Scholar 

  59. Cuzick J (2002) A brief review of the international breast cancer intervention study (IBIS), the other current breast cancer prevention trials, and proposals for future trials. Ann NY Acad Sci 2002:123–133.

    Google Scholar 

  60. Santen RJ, Manni A, Harvey H, et al (1990) Endocrine treatment of breast cancer in women. Endocrine Rev 11:1–45.

    Google Scholar 

  61. Sherman BM, Chapler FK, Crickard K, et al (1979) Endocrine consequences of continuous antiestrogen therapy with tamoxifen in premenopausal women. J Clin Invest 64:398–404.

    Article  PubMed  CAS  Google Scholar 

  62. Groom GV, Griffiths K (1976) Effect of the anti-estrogen tamoxifen on plasma levels of lutenizing hormone, follicle stimulating hormone, prolactin, oestradiol and progesterone in normal premenopausal women. J Endocrinol 70:421–428.

    Article  PubMed  CAS  Google Scholar 

  63. Liehr JG (2002) Breast carcinogenesis and its prevention by inhibition of estrogen genotoxicity. In: Miller WR, Ingle JN (eds) Endocrine Therapy in Breast Cancer. New York: Marcel Dekker, 287–301.

    Google Scholar 

  64. Miller WR, Sharpe RM (1998) Environmental estrogens and human reproductive cancers. Endocrine Related Cancer 5:69–96.

    Article  CAS  Google Scholar 

  65. Setchell KDP, Borriello SP, Hulme P, et al (1984) Nonsteroidal estrogens of dietary origin: possible roles in hormone-dependent disease. Amer J Clin Nutr 40:569–578.

    PubMed  CAS  Google Scholar 

  66. Adams JB, Garcia M, Rochefort H (1981) Estrogenic effects of physiological concentrations of 5-androstene 3β17β diol and its metabolism in MCF-7 human breast cancer cells. Cancer Res 42:470–476.

    Google Scholar 

  67. Mourisden H, Gershanovich M, Sun Y, et al (2001) Superior efficacy of letrozole versus tamoxifen as first-line therapy for postmenopausal women with advanced breast cancer: results of a Phase III study of the International Letrozole Breast Cancer Group. J Clin Oncol 19:2596–2606.

    Google Scholar 

  68. Nabholtz JM, Buzdar A, Pollak M, et al (2000) Anastrozole is superior to tamoxifen as first-line therapy for advanced breast cancer in postmenopausal women: results of a North American multicenter randomized trial. Arimidex Study Group. J Clin Oncol 18:3758–3767.

    PubMed  CAS  Google Scholar 

  69. Dixon JM, Love CD, Bellamy CO, et al (2001) Letrozole as primary medical therapy for locally advanced and large operable breast cancer. Breast Canc Res Treat 66:191–199.

    Article  CAS  Google Scholar 

  70. Eiermann W, Paepke S, Appfelstaedt J (2001) Letrozole Neoadjuvant Breast Cancer Study Group. Preoperative treatment of postmenopausal breast cancer patients with letrozole. A randomized double-blind multicenter study. Ann Oncology 12:1527–1532.

    Article  CAS  Google Scholar 

  71. The ATAC Trialist’s Group (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359:2131–2139.

    Article  Google Scholar 

  72. Fiegelson HS, Ross RK, Yu MC, et al (1996) Genetic susceptibility to cancer from exogenous and endogenous exposures. J Cell Biochem 25S:15–22.

    Article  Google Scholar 

  73. Miller WR (1996) Estrogens and endocrine therapy for breast cancer. In: Estrogen and Breast Cancer. Austin, Texas: RG Landes Company, 125–150.

    Google Scholar 

  74. Yager JD, Liehr JG (1996) Molecular mechanisms of estrogen carcinogenesis. Annual Rev Pharmacol Toxicol 36:203–232.

    Article  CAS  Google Scholar 

  75. Santen RJ, Yue, W, Naftolin F, et al (1999) The potential of aromatase inhibitors in breast cancer prevention. Endocrine Related Cancer 6:235–243.

    Article  PubMed  CAS  Google Scholar 

  76. Raftogianis R, Creveling C, Weinshilboum R, et al (2000) Estrogen metabolism by conjugation. J Natl Canc Inst Monograph 27:131–124.

    Google Scholar 

  77. Roy D, Liehr JG (1999) Estrogen, DNA damage and mutations. Mutation Res 424:107–115.

    PubMed  CAS  Google Scholar 

  78. Yue W, Santen RJ, Wang JP, et al (2003) Genotoxic metabolites of estradiol in breast: potential mechanism of estradiol induced carcinogenesis. J Steroid Biochem& Mol Biol 86:477–486.

    Article  CAS  Google Scholar 

  79. The ATAC Trialist’s Group (2002) Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 359:2131–2139.

    Article  Google Scholar 

  80. Santen RJ, Samojlik E, Wells SA (1980) Resistance of the ovary to blockade of aromatization with aminoglutethimide. J Clin Endocrinol Metab 51:473–477.

    Article  PubMed  CAS  Google Scholar 

  81. Harris AL, Dowsett M, Jeffcoate SL, et al (1982) Endocrine and therapeutic effects of aminoglutethimide in premenopausal patients with breast cancer. J Clin Endocrinol Metab 55:718–720.

    PubMed  CAS  Google Scholar 

  82. Wander HE, Blossey HC, Nagel GA (1986) Aminoglutethimide in the treatment of premenopausal patients with metastatic breast cancer. Euro J Canc Clin Oncol 22:1371–1374.

    Article  CAS  Google Scholar 

  83. Harper-Wynne C, Ross G, Sacks N, et al (2002) Effects of the aromatase inhibitor letrozole on normal breast epithelial cell proliferation and metabolic indices in postmenopausal women: a pilot study for breast cancer prevention. Cancer Epidemiol Biomarkers Prev 11:614–621.

    PubMed  CAS  Google Scholar 

  84. Goss PE (2002) Aromatase inhibitors and chemoprevention of breast cancer. In: Miller WR, Ingle JN (eds): Endocrine Therapy in Breast Cancer, Basel, CH: Marcel Dekker, 309–317.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Edinburgh Breast Unit Research Group, University of Edinburgh, Western General Hospital, Edinburgh, Scotland

    William R. Miller

Authors
  1. William R. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Division of Etiology and Prevention of Hormonal Cancers, The University of Kansas Medical Center, 3901 Rainbow Boulevard, 2010 Breidenthal, Kansas City, KS, 66160-7417

    Jonathan J. Li (Profesor of Pharmacology, Toxicology and Therapeutics and Director) & Sara A. Li (Associate Research Professor of Pharmacology, Toxicology and Therapeutics) (Profesor of Pharmacology, Toxicology and Therapeutics and Director) &  (Associate Research Professor of Pharmacology, Toxicology and Therapeutics)

  2. Departmento de Patologia, Facultad de Medicina y Odontologia, Camino de Vera s/n, Valencia, 46071, Spain

    Antonio Llombart-Bosch (Director) (Director)

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer Science+Business Media, Inc.

About this chapter

Cite this chapter

Miller, W.R. (2005). Aromatase Inhibition and Breast Cancer. In: Li, J.J., Li, S.A., Llombart-Bosch, A. (eds) Hormonal Carcinogenesis IV. Springer, Boston, MA. https://doi.org/10.1007/0-387-23761-5_14

Download citation

  • DOI: https://doi.org/10.1007/0-387-23761-5_14

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-0-387-23783-1

  • Online ISBN: 978-0-387-23761-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation