Skip to main content
SpringerLink
Log in

The role of aromatase in breast tumors

  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Aromatization of androstenedione to estrone in peripheral tissues is the major source of estrogen in postmenopausal women. The aromatase enzyme complex, which mediates the conversion of androstenedione to estrone, is present in several tissues, including adipose tissue and normal and malignant breast tissues. Aromatase activity is detectable in 50–60% of breast tumors, but the contribution that tumor aromatase makes to estrogen concentration in tumors and whether the estrogen formed is biologically important remains a controversial matter. Since concentrations of androstenedione are higher in tumors than in blood, and tumor aromatase activityin vivo may be enhanced by growth factors and by cytokines, the contribution of tumor aromatase to tumor estrogen levels may be higher than suggested by the original calculations. Measurements of tumor aromatase, tumor estrone concentrations, and DNA polymerase α activity (a marker of cellular proliferation), in samples obtained before and after treatment with the aromatase inhibitor 4-hydroxyandrostenedione, lend some support to a biological role for estrone formed locally.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. James VHT, Reed MJ: Steroid hormones and human cancer. Prog Cancer Res Ther 14:471–487, 1980.

    Google Scholar 

  2. Grodin JM, Siiteri PK, MacDonald PC: Sources of estrogen production in postmenopausal women. J Clin Endocrinol Metab 36:207–214, 1973.

    Google Scholar 

  3. Reed MJ, Hutton JD, Baxendale PM, James VHT, Jacobs HS, Fisher RP: The conversion of androstenedione to oestrone in women with endometrial cancer. J Steroid Biochem 11:905–911, 1979.

    Google Scholar 

  4. Nimrod A, Ryan KJ: Aromatization of androgens by human abdominal and breast fat tissue. J Clin Endocrinol Metab 40:367–372, 1975.

    Google Scholar 

  5. Smuk M, Schwers J: Aromatization of androstenedione by human adult liverin vitro. J Clin Endocrinol Metab 45:1009–1012, 1977.

    Google Scholar 

  6. Longcope C, Pratt JH, Schneider SH, Fineberg SE:In vivo studies on the metabolism of estrogens by muscle and adipose tissue of normal males. J Clin Endocrinol Metab 43:1134–1145, 1976.

    Google Scholar 

  7. Miller WR, Forrest APM: Oestradiol synthesis from C19 steroids by human breast cancer. Br J Cancer 33:16–18, 1974.

    Google Scholar 

  8. Vermeulen A, Deslypere JP, Paridaens R, Leclercq C, Roy F, Heuson JC: Aromatase, 17β hydroxysteroid dehydrogenase and intratissular sex hormone concentrations in cancerous and normal breast tissue in postmenopausal women. Eur J Cancer Clin Oncol 22:515–525, 1986.

    Google Scholar 

  9. James VHT, McNeill JM, Lai LC, Newton CJ, Ghilchik MW, Reed MJ: Aromatase activity in normal breast and breast tumour tissues:in vivo andin vitro studies. Steroids 50: 269–279, 1987.

    Google Scholar 

  10. Reed MJ, Cheng RW, Noel CT, Dudley HAF, James VHT: Plasma levels of estrone, estrone sulphate and estradiol and the percentage of unbound estradiol in postmenopausal women with or without breast disease. Cancer Res 43:3940–3943, 1983.

    Google Scholar 

  11. Reed MJ, Beranek PA, Cheng RW, Ghilchik MW, James VHT: The distribution of oestradiol in plasma from postmenopausal women with or without breast cancer: relationships with metabolic clearance rates of oestradiol. Int J Cancer 35: 457–460, 1985.

    Google Scholar 

  12. Bonney RC, Reed MJ, Davidson K, Beranek PA, James VHT: The relationship between 17β hydroxysteroid dehydrogenase activity and oestrogen concentrations in human breast tumours and in normal breast tissue. Clin Endocrinol 11:141–150, 1979.

    Google Scholar 

  13. Van Landeghem AAJ, Poortman J, Nabuurs M, Thijssen JHH: Endogenous concentrations and subcellular distribution of androgens in normal and malignant human breast tissue. Cancer Res 45: 2907–2912, 1985.

    Google Scholar 

  14. Fishman J, Nisselbaum JS, Menendez-Botet CJ, Schwartz MK: Estrone and estradiol content in human breast tumors: relationship to estradiol receptors. J Steroid Biochem 8: 893–896, 1977.

    Google Scholar 

  15. Edery M, Goussard J, Dehennin L, Scholler R, Reiffsteck J, Drosdowsky MA: Endogenous oestradiol 17β concentration in breast tumours determined by mass fragmentography and by radioimmunoassay: relationship to receptor content. Eur J Cancer 17:115–120, 1981.

    Google Scholar 

  16. Siiteri PK, Murai JT, Hammond GL, Nisker JA, Raymoure WJ, Kuhn RW: The serum transport of steroid hormones. Recent Prog Horm Res 38:457–503, 1982.

    Google Scholar 

  17. Pardridge WM, Mietus LJ, Frumar AM, Davidson BJ, Judd HL: Effects of human serum on transport of testosterone and estradiol into rat brain. Am J Physiol 239:E103-E108, 1980.

    Google Scholar 

  18. Rosner W: The functions of corticosteroid-binding globulin and sex hormone-binding globulin: recent advances. Endocrinol Rev 11:80–91, 1990.

    Google Scholar 

  19. Bradlow HL: A reassessment of the role of breast tumor aromatase. Cancer Res (Suppl) 42:3382s-3386s, 1992.

    Google Scholar 

  20. Reed MJ, Owen AM, Lai LC, Coldham NG, Ghilchik MW, Shaikh NA, James VHT:In situ oestrone synthesis in normal breast and breast tumour tissues: effect of treatment with 4-hydroxyandrostenedione. Int J Cancer 44:233–237, 1989.

    Google Scholar 

  21. Reed MJ, Coldham NG, Patel S, Ghilchik MW, James VHT: Interleukin-1 and interleukin-6 in breast cyst fluid: their role in regulating aromatase activity in breast cancer cells. J Endocrinol 132:R5-R8, 1992.

    Google Scholar 

  22. Reed MJ, Topping L, Coldham NG, Purohit A, Ghilchik MW, James VHT: Control of aromatase activity in breast cancer cells: the role of cytokines and growth factors. J Steroid Biochem Molec Biol 44:589- 596, 1993.

    Google Scholar 

  23. Leuprasitsakul P, Longcope C: Aromatase activity in human adipose tissue stromal cells: the effect of fetal bovine serum fractions on dexamethasone-stimulated aromatization. J Steroid Biochem Molec Biol 39:353–357, 1991.

    Google Scholar 

  24. Miller WR, O'Neill JS: The importance of local synthesis of estrogen within the breast. Steroids 50: 537–547, 1987.

    Google Scholar 

  25. Singh A, Ghilchik MW, Patel SR, Blench I, Morris HR, Reed MJ: Identification of albumin in breast tumor cytosol as a factor involved in the stimulation of estradiol 17β hydroxysteroid dehydrogenase (reductive) activity. Molec Cell Endocrinol 83:85–92, 1992.

    Google Scholar 

  26. Miller WR, Mullen P: Factors influencing aromatase activity in the breast. J Steroid Biochem Molec Biol 44: 597–604, 1993.

    Google Scholar 

  27. Simpson ER, Ackerman GE, Smith ME, Mendelson CR: Estrogen formation in stromal cells of adipose tissue in women: induction by glucocorticoids. Proc Natl Acad Sci USA 78:5690–5694, 1981.

    Google Scholar 

  28. Folkerd EJ, James VHT: Aromatization of steroids in peripheral tissues. J Steroid Biochem 19:687–690, 1983.

    Google Scholar 

  29. Rizkallah TH, Tovell HMM, Kelley WG: Production of estrone and fractional conversion of circulating androstenedione to estrone in women with endometrial carcinoma. J Clin Endocrinol Metab 40:1045–1056, 1975.

    Google Scholar 

  30. Reed MJ, Beranek PA, Franks S, James VHT: The effect of glucocorticoids on thein vivo conversion of androstenedione to oestrone. Horm Metabol Res 18: 635–637, 1986.

    Google Scholar 

  31. Longcope C: Peripheral aromatization: studies on controlling factors. Steroids 50:253–267, 1987.

    Google Scholar 

  32. Santner SJ, Chen S, Zhou D, Korsunsky Z, Martel J, Santen RJ: Effect of androstenedione on growth of untransfected and aromatase-transfected MCF-7 cells in culture. J Steroid Biochem Molec Biol 44:611–616, 1993.

    Google Scholar 

  33. Esteban JM, Warsi Z, Haniu M, Hall P, Shively JE, Chen S: Detection of intratumoral aromatase in breast carcinomas. An immunohistochemical study with clinicopathologic correlation. Am J Path 140:337–343, 1992.

    Google Scholar 

  34. Roselli CE, Ellinwood WE, Resko JA: Regulation of brain aromatase in rats. Endocrinology 11:192–199, 1983.

    Google Scholar 

  35. Connolly PB, Roselli CE, Resko JA: Aromatase activity in adult guinea pig brain is androgen dependent. Biol Reprod 43:698–703, 1990.

    Google Scholar 

  36. Elbrecht A, Smith RG: Aromatase enzyme and sex determination in chickens. Science 255:467–470, 1992.

    Google Scholar 

  37. Purohit A, Flanagan AM, Reed MJ: Estrogen synthesis by osteoblast cell lines. Endocrinology 131: 2027–2029, 1992.

    Google Scholar 

  38. Zhou D, Pompou D, Chen S: Stable expression of human aromatase complementary DNA in mammalian cells: A useful system for aromatase inhibitor screening. Cancer Res 50:6949–6954, 1990.

    Google Scholar 

  39. Kitawaki J, Fukuoka M, Yamamoto T, Honjo H, Okada H: Contribution of aromatase to the deoxyribonucleic acid synthesis of MCF-7 human breast cancer cells and its suppression by aromatase inhibitors. J Steroid Biochem Molec Biol 42:267–277, 1992.

    Google Scholar 

  40. Leavitt WW, Chen TJ, Do YS, Carlton BD, Allen TC: Biology of progesterone receptors.In: O'Malley BW, Birnbaumer L (eds) Receptors and Hormone Action, Vol II. Academic Press, 1978.

  41. Tilson-Mallett N, Santner SJ, Feil PD, Santen RJ: Biological significance of aromatase activity in human breast tumors. J Clin Endocrinol Metab 57:1125–1128, 1983.

    Google Scholar 

  42. James VHT, Reed MJ, Adams EF, Ghilchik M, Lai LC, Coldham NG, Newton CJ, Purohit A, Owen AM, Singh A, Islam S: Oestrogen uptake and metabolismin vivo. Proc Royal Soc Edinburgh 95B:185–193, 1989.

    Google Scholar 

  43. Bezwoda WR, Mansoor N, Dansey R: Correlation of breast tumour aromatase activity and response to aromatase inhibition with aminoglutethimide. Oncology 44:345–349, 1987.

    Google Scholar 

  44. Lipton A, Santen RJ, Santner SJ, Harvey HA, White-Hershey D, Bartholomew MJ, Sharkey FE: Correlation of aromatase activity with histological differentiation of breast cancer — a morphometric analysis. Breast Cancer Res Treat 12:31–35, 1988.

    Google Scholar 

  45. Bolufer P, Ricart E, Lluch A, Vazquez C, Rodriguez A, Ruiz A, Llopis F, Garcia-Conde J, Romero R: Aromatase activity and estradiol in human breast cancer: its relationship to estradiol and epidermal growth factor receptors and to tumor-node-metastasis staging. J Clin Oncol 10:438–446, 1992.

    Google Scholar 

  46. Silva MC, Rowlands MG, Dowsett D, Gusterson B, McKinna JA, Fryatt I, Coombes RC: Intratumoral aromatase as a prognostic factor in human breast carcinoma. Cancer Res 49:2588–2591, 1989.

    Google Scholar 

  47. Santen RJ, Santner SJ, Davis B, Veldhuis J, Samojlik E, Ruby E: Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 47:1257–1265, 1978.

    Google Scholar 

  48. Reed MJ, Lai LC, Owen AM, Singh A, Coldham NG, Purohit A, Ghilchik MW, Shaikh NA, James VHT: Effect of treatment with 4-hydroxyandrostenedione on the peripheral conversion of androstenedione to estrone andin vivo tumor aromatase activity in postmenopausal women with breast cancer. Cancer Res 50:193–196, 1990.

    Google Scholar 

  49. Miller WR:In vitro andin vivo effects of 4-hydroxyandrostenedione on steroid and tumor metabolism.In: Coombes RC, Dowsett M (eds) 4-Hydroxyandrostenedione — A New Approach to Hormone-Dependent Cancer. Royal Soc Med Int Cong Ser 180, 1991, pp 45–49.

  50. Reed MJ, Aherne GW, Ghilchik MW, Patel S, Chakraborty J: Concentrations of oestrone and 4-hydroxyandrostenedione in malignant and normal breast tissues. Int J Cancer 49:562–565, 1991.

    Google Scholar 

  51. Coldham NG, Lai LC, Ghilchik MW, Walker MM, James VHT, Reed MJ: The effect of treatment with 4-hydroxyandrostenedione or medroxyprogesterone acetate on human breast tumour regression. Anticancer Res 13:753–758, 1993.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Unit of Metabolic Medicine, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, Norfolk Place, W2 1PG, London, UK

    M. J. Reed

Authors
  1. M. J. Reed
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Reed, M.J. The role of aromatase in breast tumors. Breast Cancer Res Tr 30, 7–17 (1994). https://doi.org/10.1007/BF00682737

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00682737

Key words

Search

Navigation