Intra-Mammary Steroid Transformation: Implications for Tumorigenesis and Natural Progression

  • W. R. Miller
Part of the Reproductive Biology book series (RBIO)


Steroid hormones are heavily implicated in the development and continued growth of breast cancer. Castration, especially early in life has a major impact in reducing risk of breast cancer (Feinleib, 1968), a protection which may be abolished if replacement steroids are administered. Similarly, it has long been recognized that therapy based on steroid hormone deprivation may be associated with regression of established breast cancer. The presence of estrogen receptors in hormone dependent cancers (McGuire et al., 1975) and the effects of estrogen and anti-estrogen in cultures of breast cancer cells (Lippmann et al., 1983) point to the central role of estradiol amongst the steroid hormones. More recent work (Lippman et al., 1986) has suggested that the growth promoting properties of estrogen may at least in part be due to their ability to stimulate tumor cell secretion of polypeptide factors which possess the potential to trigger cell division in an autocrine or paracrine fashion (Figure 1A). It has also been suggested that hormone independent growth simply reflects an estrogen by-pass resulting from cellular adaptation towards the constitutive production of the same or similar growth factors (Dickson and Lippman, 1986).


Breast Cancer Adipose Tissue Estrogen Receptor Aromatase Activity Steroid Metabolism 
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  1. Abul-Hajj Y.J. 1975. Metabolism of dehydroepiandrosterone by hormone dependent and independent human breast cancer. Steroids 26:488.PubMedCrossRefGoogle Scholar
  2. Abul-Hajj Y.J., Iverson R. and Kiang D.T. 1979. Aromatization of androgens by human breast cancer. Steroids 33:205.PubMedCrossRefGoogle Scholar
  3. Beranek P.A., Fokerd E.J., Newton C.J., Reed M.J., Chilchick M.W. and James V.H.T. 1985. The relationship between 17β-hydroxysteroid dehydrogenase and breast tumour site and size. Int. J. Cancer. 36:685.PubMedCrossRefGoogle Scholar
  4. Bonney R.C., Reed M.J., Davidson K., Beranek P.A. and James V.H.T. 1983. The relationship between 17β-hydroxysteroid dehydrogenase activity and oestrogen concentration in human breast tumours and in normal breast. Clin. Endocrinol. 19:727.CrossRefGoogle Scholar
  5. Buirchell B.J. and Hahnel R. 1985. Metabolism of estradiol-17β in human endometrium during the menstrual cycle. J. Steroid Biochem. 6:1489.CrossRefGoogle Scholar
  6. Channing C.P. and Segal S. 1981. Intraovarian control mechanisms. Plenum Press: New York.Google Scholar
  7. Dickson R.B. and Lippman M.E. 1986. Hormonal control of human breast cancer cell lines. Cancer Surv. 5:617.PubMedGoogle Scholar
  8. De Ome K.B., Franklin L.J. and Bern H.A. 1959. Development of mammary tumours from hyperplastic nodules transplanted into gland free mammary fat pads of female C3H mice. Cancer Research 19:515.Google Scholar
  9. Deslypere J.P., Verdonck L. and Vermeulen A. 1985. Fat tissue: a steroid reservoir and site of steroid metabolism. J. Clin. Endocrinol. Metab. 61:564.PubMedCrossRefGoogle Scholar
  10. Durnberger H., Heuberger B., Schwartz P., Wasner G. and Kratochwil K. 1978. Mesenchyme-mediated effect of testosterone on embryonic mammary epithelium. Cancer Research 38:4066.PubMedGoogle Scholar
  11. Durning P., Schor S.L. and Sellwood A.B. 1984. Fibroblasts from patients with breast cancer show abnormal migratory behaviours in vitro. The Lancet 2:890.CrossRefGoogle Scholar
  12. De Waard F. 1983. Epidemiology of breast cancer: a review. Eur. J. Cancer Clin. Oncol. 19:1671.PubMedCrossRefGoogle Scholar
  13. Feinleib M. 1968. Breast cancer and artificial menopause: A cohort study. J. Natl. Cancer Inst. 41:315.PubMedGoogle Scholar
  14. Haslam S.Z. 1986. Mammary fibroblast influence on normal mouse mammary epithelial cell response to oestrogen in vitro. Cancer Research 46:310.PubMedGoogle Scholar
  15. Hawkins R.A., Thijssen J.H.H. and Miller W.R. 1987. Die bedeutung der Aromatase-und Sulfatasestoffwechselwege fur die intrazellulare Ostrogensynthese beim Mammakarzinom postmenopausoler Frauen. Act. Onkol. 38:3.Google Scholar
  16. Hawkins R.A., Roberts M.M. and Forrest A.P.M. 1980. Oestrogen receptors and breast cancer: current status. Br. J. Surg. 67:153.PubMedCrossRefGoogle Scholar
  17. Horgan K., Jones D.L. and Mansel R.E. 1987. Mitogenicity of human fibroblasts in vivo for human breast cancer cells. Br. J. Surg. 74:227.PubMedCrossRefGoogle Scholar
  18. James V.H.T. 1989. Oestrogen uptake and metabolism in vivo. Proc. Roy. Soc. (Edin). (in press).Google Scholar
  19. Lawrence B.V., Lipton A., Harvey H.A., Santen R.J., Wells S.A., Cox C.E., White D.S. and Smart E.E. 1980. Influence of estrogen receptor status on response of metastatic breast cancer to aminoglutethimide therapy. Cancer 45:786.PubMedCrossRefGoogle Scholar
  20. Li K. and Adams J.B. 1981. Aromatization of testosterone and oestrogen receptors levels in human breast cancer. J. Steroid Biochem. 14:269.PubMedCrossRefGoogle Scholar
  21. Lippman M.E., Bolan G. and Huff K. 1983. The effects of estrogens and antiestrogens on hormone-responsive human breast cancer cell line. Cancer Research 43:1244.Google Scholar
  22. McGuire W.L., Carbone P.P., Sears M.E. and Escher G.C. 1975. Estrogen receptors in human breast cancer: an overview. In: “Estrogen Receptors Human Breast Cancer”, (W.L. McGuire, P.P. Carbone and E.P. Vollmer, eds.), Raven Press, New York, p.1.Google Scholar
  23. McNeil J.M., Reed M.J., Beranek P.A., Bonney R.C., Chilchick M.W., Robinson D.J. and James V.H.T. 1986(a). A comparison of the in vivo uptake and metabolism of 3H-oestrone and 3H oestradiol by normal breast and breast tumour tissue in postmenopausal women. Int. J. Cancer 38:193.CrossRefGoogle Scholar
  24. McNeil J.M., Reed M.J., Beranek P.A., Newton C.J., Chilchik M.W. and James V.H.T. 1986(b). The effect of epidermal growth factor, transforming growth factor and breast tumour homogenates on the activity of oestradiol 17α-hydroxysteroid dehydrogenase in adipose tissue. Cancer Reports 31:213.Google Scholar
  25. Miller W.R. and O’Neill J.S. 1989. The relevance of local oestrogen metabolism within the breast. Proc. Roy. Soc. (Edin). (in press).Google Scholar
  26. O’Neill J.S. and Miller W.R. 1987. Aromatase activity in breast adipose tissue from women with benign and malignant breast disease. Br. J. Cancer 56:601.PubMedCrossRefGoogle Scholar
  27. O’Neill J.S., Elton R.A. and Miller W.R. 1988. Aromatase activity in adipose tissue from breast quadrants: a link with tumour site. Br. Med. J. 296:741.CrossRefGoogle Scholar
  28. Perel E., Wilkin D. and Killinger D.W. 1980. The conversion of androstenedione to estrone, estradiol and testosterone in breast tissue. J. steroid Biochem. 13:89.PubMedCrossRefGoogle Scholar
  29. Perel E., Blackstein M.E. and Killinger D.W. 1983. Control of aromatase activity in cultured human breast carcinoma cells. J. Steroid Biochem. 19: suppl 645 (Abs. 191).CrossRefGoogle Scholar
  30. Pollow K., Boquoi E., Banmann J., Schmidt-Gollwitzer M. and Pollow B. 1977. Comparison of the in vitro conversion of estradiol to estrone of normal and neoplastic human breast tissue. Mol. Cell. Endocrinol. 3:33.Google Scholar
  31. Preschtel K. 1977. Benign disease of the female breast: histology, normal and abnormal. In: “Proceedings of the VIIIth World Congress on Gynaecology and Obstetrics”, (L. Castelazo-Ayalah and C. MacGregor, eds.). p.135.Google Scholar
  32. Rozengurt E., Sinnett-Smith J. and Taylor-Papadimitriou J. 1985. Production of PDGF-like growth factor by breast cancer cell lines. Int. J. Cancer 36:247.PubMedCrossRefGoogle Scholar
  33. Schor S.L., Schor A.M., Howell A. and Crowther D. 1987. Hypothesis: the persistent expression of fetal-like phenotypic characteristics by fibroblasts is associated with an increased susceptibility to neoplastic disease. Exp. Cell Biol. 55:11.PubMedGoogle Scholar
  34. Simpson E.R. and Mendelson C.R. 1987. Effect of aging and obesity on aromatase activity of human adipose cells. Am. J. Clin. Nut. 45:290.Google Scholar
  35. Strombeck J.O. 1944. Macromastia in women and its surgical treatment: a clinical study based on 1042 cases. Acta Chir. Scand. suppl 341:33.Google Scholar
  36. Tanzer M.L. and Spring-Mills E. 1984. Breast cancer, epithelial cells and extracellular matrix. J. Natl. Cancer Inst. 73:999.Google Scholar
  37. Tilson-Mallet N., Santner S.J., Feil P.D. and Santen R.J. 1983. Biological significance of aromatase activity in human breast tumours. J. Clin. Endocrinol. Metab. 57:1125.CrossRefGoogle Scholar
  38. Van Landegham A.A.J., Poortman J., Nabuurs M. and Thyssen J.H.H. 1985. Endogenous concentration and subcellular distribution of estrogens in normal and malignant breast tissue. Cancer Research 45:2900.Google Scholar
  39. Vermeulen A. 1986. Human mammary cancer as a site of sex steroid metabolism. Cancer Surv. 5:585.PubMedGoogle Scholar
  40. Vermeulen A., Deslypere J.P., Paridaens R., Leclerq C., Roy F. and Heuson J.C. 1986. Aromatase, 17β-hydroxysteroid dehydrogenase and intratissular sex hormone concentration in cancerous and normal glandular breast tissue in postmenopausal women. Eur. J. Cancer Clin. Oncol. 22:515.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • W. R. Miller
    • 1
  1. 1.University Department of SurgeryRoyal InfirmaryEdinburghScotland

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