Hostname: page-component-78c5997874-ndw9j Total loading time: 0 Render date: 2024-11-02T22:56:07.973Z Has data issue: false hasContentIssue false
  • English
  • Français

The relevance of local oestrogen metabolism within the breast

Published online by Cambridge University Press:  05 December 2011

W. R. Miller  and
J. S. O'Neill
W. R. Miller
Affiliation:
Department of Surgery, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, Scotland, U.K.
J. S. O'Neill
Affiliation:
Department of Surgery, University of Edinburgh, Royal Infirmary, Lauriston Place, Edinburgh EH3 9YW, Scotland, U.K.
Get access

Synopsis

Ovarian oestrogens appear to have a central role in the development of the breast. However, peripheral tissues including the breast and its tumours have the potential to synthesise and metabolise oestrogens. When ovarian secretion of hormones is low, for example, after the menopause, such extra-gonadal steroidogenesis may assume biological significance.

While no individual steroid conversion in the breast has been shown to correlate with levels of endogenous oestrogens, certain positive associations have been observed between enzyme activities and the presence, stage and hormone dependence of breast cancer.

Thus biosynthesis of oestrogen (aromatisation) in breast fat is significantly higher in patients with breast cancer as compared to that from women with benign breast disease. Within the breasts of women with cancer, oestrogen biosynthesis is enhanced in quadrants bearing tumour. In contrast, levels of 17β-hydroxysteroid dehydrogenase are not associated with the presence of malignancy, but in women with breast cancer, activity is significantly higher in breast fat of patients with large tumours and those with nodal metastasis. There is also evidence that oestrogen sulphurylation in breast cancer is associated with hormone dependence and among postmenopausal patients with oestrogen-receptor-positive tumours, response to the aromatase inhibitor, aminoglutethimide, is restricted to cancers possessing aromatase activity.

Type
Research Article
Information
Proceedings of the Royal Society of Edinburgh, Section B: Biological Sciences , Volume 95: Oestrogen and the Human Breast , 1989 , pp. 203 - 217
Copyright
Copyright © Royal Society of Edinburgh 1989

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Abul-Hajj, Y. J., Iverson, R. & Kiang, D. T. 1979. Aromatization of androgens by human breast cancer. Steroids 33, 205–222.CrossRefGoogle ScholarPubMed
Adams, J. B., Pewnim, T., Chandra, D. P., Archibald, L. & San Foo, M. 1979. A correlation between estrogen sulfotransferase levels and estrogen receptor status in human primary breast carcinoma. Cancer Research 39, 5124–5126.Google ScholarPubMed
Beranek, P. A., Folkerd, E. J., Ghilchick, M. W. & James, V. H. T. 1984. 17β-hydroxysteroid dehydrogenase and aromatase activity in breast fat from women with benign and malignant breast tumours. Clinical Endocrinology 29, 205–212.CrossRefGoogle Scholar
Beranek, P. A., Folkerd, E. J., Newton, C. J., Reed, M. J., Ghilchick, M. W. & James, V. H. T. 1985. The relationship between 17β-hydroxysteroid dehydrogenase and breast tumour site and size. International Journal of Cancer 36, 685–688.CrossRefGoogle Scholar
Bolt, H. M. & Gobel, P. 1972. Formation of oestrogens from androgens by human subcutaneous adipose tissue in vitro. Hormone and Metabolic Research 4, 312–313.CrossRefGoogle ScholarPubMed
Bonney, R. C., Reed, M. J., Davidson, K., Beranek, P. A. & James, V. H. T. 1983. The relationship between 17β-hydroxysteroid dehydrogenase activity and oestrogen concentration in human breast tumours and in normal breast. Clinical Endocrinology 19, 727–739.CrossRefGoogle Scholar
Dao, T. L. & Libby, P. R. 1972. Steroid sulfate formation in human breast tumors and hormone dependency. In Estrogen Target Tissue and Neoplasia, Dao, T. L., pp. 181–200. Chicago: Chicago University Press.Google Scholar
De Ome, K. B., Franklin, L. J. & 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, 515–520.Google Scholar
Edery, M., Goussard, J., Dehennin, L., Scholler, R., Reiffsteck, J. & Drosdowsky, M.A. 1981. Endogenous oestradiol-17β concentration in breast tumours determined by mass fragmentography and by radio-immunoassay: relationship to receptor content. European Journal of Cancer 17, 115–120.CrossRefGoogle Scholar
Feher, T., Bodrogi, L., Valient, K. & Ribai, Z. 1982. Role of human adipose tissue in the production and metabolism of steroid hormones. Endocrinologie 80, 173–180.Google ScholarPubMed
Feinleib, M. 1968. Breast cancer and artificial menopause: a cohort study. Journal of the National Cancer Institute 44, 315–329.Google Scholar
Fishman, J. Nisselbaum, J. S., Menendez-Botet, C. J. & Schwartz, M. K. 1977. Estrone and estradiol content in human-breast tumours: relationship to estradiol receptors. Journal of Steroid Biochemistry 8, 893–896.CrossRefGoogle ScholarPubMed
Geier, A., Horn, H., Levij, I. S., Lichstein, E. & Finkelstein, M. 1975. The metabolism of3H-estradiol-17β in human breast cancer in organ culture. European Journal of Cancer 11, 127–130.CrossRefGoogle Scholar
Hawkins, R. A., Thomson, M. L. & Killen, E. 1985. Oestrogen sulphate, adipose tissue and breast cancer. Breast Cancer Research and Treatment 6, 75–87.CrossRefGoogle ScholarPubMed
Hawkins, R. A., Thijssen, J. H. H. & Miller, W. R. 1987. Die bedeutung der Aromatase und Sulfatase stoffwech-selwege für die intrazellulare Oestrogensynthese beim Mammakarzinom postmenopausaler Frauen. Actuelle Onkologie 38, 3–10.Google Scholar
James, V. H. T., Reed, M. J., Adams, E. F., Ghilchik, M., Lai, L. C., Coldham, N. G., Newton, C. J., Purohit, A., Owen, A. M., Singh, A. & Islam, S. 1989. Oestrogen uptake and metabolism in vivo. Proceedings of the Royal Society of Edinburgh 95B, 185–193.Google Scholar
Leung, B. B., Fletcher, W. S., Lindell, T. D., Wood, D. C. & Krippach, W. W. 1973. Predictability of response to endocrine ablation in advanced breast cancer. Archives of Surgery 106, 515–519.CrossRefGoogle Scholar
Li, K. & Adams, J. B. 1981. Aromatization of testosterone and oestrogen receptor levels in human breast cancer. Journal of Steroid Biochemistry 14, 269–272.CrossRefGoogle ScholarPubMed
Lippman, M. E., Dickson, R. B., Bates, S. Knabbe, C., Huff, K., Swain, S., McManaway, M., Bronzert, D., Kasid, A. & Gelman, E. P. 1986. Autocrine and paracrine growth regulation of human breast cancer. Breast Cancer Research and Treatment 7, 59–70.CrossRefGoogle ScholarPubMed
McGuire, W. L., Carbone, P. P., Sears, M. E. & Esher, G. C. 1975. Estrogen receptors in human breast cancer: an overview. In Estrogen Receptors in Human Breast Cancer, eds. McGuire, W. L., Carbone, P. P. & Vollmer, E. P., pp. 1–8. New York: Raven Press.Google ScholarPubMed
McNeil, J. M., Reed, M. J., Beranek, P. A., Bonney, R. C., Ghilchick, M. W., Robinson, D. J. & James, V. H. T. 1986a. 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. International Journal of Cancer 38, 193–196.CrossRefGoogle Scholar
McNeil, J. M., Reed, M. J., Beranek, P. A., Newton, C. J., Ghilchick, M. W. & James, V. H. T. 1986b. The effect of epidermal growth factor, transforming growth factor and breast tumour homogenates on the activity of oestradiol 17β-hydroxysteroid dehydrogenase in adipose tissue. Cancer Letters 31, 213–219.CrossRefGoogle Scholar
Miller, W. R. 1986. Steroid metabolism in breast cancer. In Breast Cancer: Treatment and Prognosis, ed. Stoll, B. A., pp. 156–172. Oxford: Blackwell Scientific Publications 12.Google Scholar
Miller, W. R. & Forrest, A. P. M. 1974. Oestradiol synthesis from C19 steroids by human breast cancer. British Journal of Cancer 33, 16–18.Google Scholar
Miller, W. R. & O'Neill, J. 1987. Mammary steroidogenesis: therapeutic implications. Nuclear Medicine and Biology 14, 369–376.Google ScholarPubMed
Millington, D., Jenner, D. A., Jones, T. & Griffiths, K. 1974. Endogenous steroid concentrations in human breast tumours determined by high-resolution mass fragmentography. Biochemical Journal 139, 473–475.CrossRefGoogle ScholarPubMed
Nimrod, A. & Ryan, K. J. 1975. Aromatization of androstenedione by human abdominal and breast fat tissue. Journal of Clinical Endocrinology and Metabolism 40, 367–372.CrossRefGoogle ScholarPubMed
O'Neill, J. S., Elton, R. A. & Miller, W. R. 1988. Aromatase activity in adipose tissue from breast quadrants: a link with tumour site. British Medical Journal 296, 741–743.CrossRefGoogle ScholarPubMed
O'Neill, J. S. & Miller, W. R. 1987. Aromatase activity in breast adipose tissue from women with benign and malignant breast disease. British Journal of Cancer 56, 601–604.CrossRefGoogle Scholar
Perel, E., Wilkin, D. & Killinger, D. W. 1980. The conversion of androstenedione to estrone, estradiol and testosterone in breast tissue. Journal of Steroid Biochemistry 13, 89–94.CrossRefGoogle ScholarPubMed
Perel, E. & Killinger, D. W. 1979. The interconversion and aromatization of androgens by human adipose tissue. Journal of Steroid Biochemistry 10, 623–627.CrossRefGoogle ScholarPubMed
Pollow, K., Buquoi, E., Baumann, J., Schmidt-Gollwitzer, M. & Pollow, B. 1977. Comparison of the in vitro conversion of estradiol to estrone in normal and neoplastic human breast tissue. Molecular and Cellular Endocrinology 6, 333–348.CrossRefGoogle ScholarPubMed
Preschtel, K. 1977. Benign disease of the female breast: histology, normal and abnormal. In Proceedings of the VIIIth World Congress on Gynaecology and Obstetrics, eds Castelazo-Ayala, L. & McGregor, C., pp. 135–138. Amsterdam: Excerpta Medica.Google Scholar
Santner, S. J., Leszozynski, D., Wright, C., Mann, A., Feil, P. D. & Santen, R. J. 1986. Estrone sulphate: a potential source of estradiol in human breast cancer tissues. Breast Cancer Research and Treatment 7, 35–44.CrossRefGoogle ScholarPubMed
Sasano, N., Tateno, H. & Stemmerman, G. N. 1978. Volume and hyperplastic lesions in breast of Japanese women in Hawaii and Japan. Preventative Medicine 7, 196–204.CrossRefGoogle ScholarPubMed
Schweikert, H. U., Milewich, L. & Wilson, J. D. 1976. Aromatization of androstenedione by cultured human fibroblasts. Journal of Clinical Endocrinology and Metabolism 43, 785–795.CrossRefGoogle ScholarPubMed
Simpson, E. R. & Mendelson, C. R. 1987. Effect of aging and obesity on aromatase activity of human adipose cells. American Journal of Clinical Nutrition 45, 290–295.CrossRefGoogle ScholarPubMed
Strombeck, J. O. 1964. Macromastia in women and its surgical treatment: a clinical study based on 1042 cases. Acta Chirugia Scandanavia (Supplement) 341, 33–36.Google Scholar
Tilson-Mallet, N., Santner, S. J., Feil, P. D. & Santen, R. J. 1983. Biological significance of aromatase activity in human breast tumours. Journal of Clinical Endocrinology and Metabolism 57, 1125–1128.CrossRefGoogle Scholar
Van Landeghem, A. A. J., Poortman, J., Nabuurs, M. & Thyssen, J. H. H. 1985. Endogenous concentration and subcellular distribution of estrogens in normal and malignant breast tissue. Cancer Research 45, 2900–2904.Google Scholar
Vermeulen, A. 1986. Human mammary cancer as a site of sex steroid metabolism. Cancer Surveys 5, 585–595.Google ScholarPubMed
Vermeulen, A., Deslypere, J. P., Paridaens, R., Leclercq, C., Roy, F. & Heuson, J. C. 1986. Aromatase, 17β-hydroxysteroid dehydrogenase and intratissular sex hormone concentration in cancerous and normal glandular breast tissue in postmenopausal women. European Journal of Cancer and Clinical Oncology 22, 515–525.CrossRefGoogle Scholar
Wellings, S. R., Jensen, H. M. & Marcum, R. G. 1975. An atlas of subgross pathology of the human breast with special reference to possible precancerous conditions. Journal of the National Cancer Institute 55, 231–273.Google Scholar