Hostname: page-component-669899f699-qzcqf Total loading time: 0 Render date: 2025-05-02T20:44:42.307Z Has data issue: false hasContentIssue false
  • English
  • Français

Current controversies in the role of antioestrogens in the treatment of carcinoma of the breast

Published online by Cambridge University Press:  05 December 2011

M. Baum ,
S. C. A. Fraser ,
A. A. Colletta  and
S. R. Ebbs
M. Baum
Affiliation:
Department of Surgery, Rayne Institute, King's College Hospital School of Medicine and Dentistry, 123 Coldharbour Lane, London SE5 9NU, U.K.
S. C. A. Fraser
Affiliation:
Department of Surgery, Rayne Institute, King's College Hospital School of Medicine and Dentistry, 123 Coldharbour Lane, London SE5 9NU, U.K.
A. A. Colletta
Affiliation:
Department of Surgery, Rayne Institute, King's College Hospital School of Medicine and Dentistry, 123 Coldharbour Lane, London SE5 9NU, U.K.
S. R. Ebbs
Affiliation:
Department of Surgery, Rayne Institute, King's College Hospital School of Medicine and Dentistry, 123 Coldharbour Lane, London SE5 9NU, U.K.
Get access

Synopsis

The development of the triphenylethylene derivatives has been a major advance in the treatment of breast carcinoma, due to their low toxicity. Currently there is controversy not only about their mode of action but in three main areas of clinical practice: (A) adjuvant therapy in premenopausal and oestrogen receptor-negative cases; (B) primary therapy in the elderly; (C) the prevention of breast cancer.

The United States' National Institute of Health consensus of 1985 that adjuvant tamoxifen be confined to postmenopausal women with positive nodes and ER positive tumours has been refuted by randomised clinical trials. The evidence that ER negative tumours also respond to tamoxifen has added to laboratory evidence that tamoxifen acts other than purely by oestrogen antagonism at the ER.

The use of tamoxifen as sole treatment in primary breast cancer in the elderly is being evaluated in randomised clinical trials. Two that have been reported so far have flaws which make their contradictory conclusions difficult to assess.

Recent results from the CRC trial suggest that tamoxifen has more benefit than simply preventing cancer deaths and clarification of the effects of triphenylethylenes on bone metabolism and the cardiovascular system may strengthen the case for a trial of prophylactic tamoxifen in those at risk of developing breast carcinoma.

Type
Research Article
Information
Proceedings of the Royal Society of Edinburgh, Section B: Biological Sciences , Volume 95: Oestrogen and the Human Breast , 1989 , pp. 221 - 229
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.)

Article purchase

Temporarily unavailable

References

Allan, S. G., Rodger, A., Smyth, J. F., Leonard, R. C. F., Chetty, U. & Forrest, A. P. M. 1985. Tamoxifen as primary treatment of breast cancer in elderly or frail patients: A practical management. British Medical Journal 290, 358.Google Scholar
Beaglehole, R. 1988. Oestrogens and cardiovascular disease. British Medical Journal 297, 571–572.Google Scholar
Bradbeer, J. W. & Kyngdon, J. 1983. Primary treatment of breast cancer in elderly women with tamoxifen. Clinics in Oncology 9, 31–34.Google Scholar
CRC Adjuvant Breast Trial Working Party 1988. Cyclophosphamide and tamoxifen as adjuvant therapies in the management of breast cancer. British Journal of Cancer 57, 604–607.Google Scholar
Christiansen, C., Christiansen, M. S. & Transbol, I. 1981. Bone mass in postmenopausal women after withdrawal of oestrogen/gestagen replacement therapy. Lancet (i), 459–61.Google Scholar
Cole, M. P., Jones, C. T. A. & Todd, I. D. H. 1971. A new anti-oestrogen agent in late breast cancer. An elderly clinical appraisal of ICI 46474. British Journal of Cancer 25, 270–275.Google Scholar
Cunha, G. R., Chung, K. W. K., Shannon, J. M., Taguchi, O. & Fugii, H. 1983. Hormone-induced morphogenesis and growth: role of mesenchymal-epithelial interactions. Recent progress in Hormone Research 39, 559–598.Google ScholarPubMed
Cusick, J., Wang, D. Y. & Bulbrook, R. D. 1986. The prevention of breast cancer. Lancet (i), 83–86.Google Scholar
Cusick, J. & Baum, M. 1985. Tamoxifen and contralateral breast cancer. Lancet (ii), 282 (letter).Google Scholar
Dickson, R. B., Huff, K. K., Spencer, E. M. & Lippman, M. E. 1986. Induction of epidermal growth factor-related polypeptides by 17-beta oestradiol in MCF-7 human breast cancer cells. Endocrinology 118, 138–142.Google Scholar
Early Breast Cancer Trialists' Collaborative Group 1989. Effects of adjuvant tamoxifen and of cytotoxic therapy on mortality in early breast cancer: An overview among 28896 women. New England Journal of Medicine 319, 1681–1692.Google Scholar
Ebbs, S. R., Roberts, J. V. & Baum, M. 1987. Alternative mechanisms of action of “anti-oestrogens” in breast cancer. Lancet (ii), 621.Google Scholar
Enami, J., Enami, S. & Koga, M. 1983. Growth of normal and neoplastic mouse mammary epithelial cells in primary culture: stimulation by conditioned medium from mouse mammary fibroblasts. Gann 74, 845–853.Google Scholar
Eriksen, E. F., Colvard, D. S., Berg, N. J., Graham, M. L., Mann, K. G., Spelsberg, T. C. & Riggs, B. L. 1988. Evidence of estrogen receptors in normal human osteoblast-like cells. Science 241, 84–86.Google Scholar
Fentiman, I. S., Caleffi, M., Murby, B. & Fogelman, I. 1988. Dosage, duration and short term effect on bone mineral content of tamoxifen treatment of mastalgia. British Journal of Clinical Practice (Suppl) 56.Google Scholar
Gazet, J.-C., Markopoulos, Ch., Ford, H. T., Coombes, R. C., Bland, J. M. & Dixon, R. C. 1988. Prospective randomised trial of tamoxifen versus surgery in elderly patients with breast cancer. Lancet (i), 679–681.Google Scholar
Goldhirsch, A., Gelber, R. D. & Davis, B. W. 1986. Adjuvant chemotherapy trials in breast cancer: an appraisal and lessons for patient care outside the trials. In Breast Disease, ed. Forbes, J. G., pp. 123–138. Edinburgh: Churchill-Livingstone.Google Scholar
Gotfredsen, A., Christiansen, C. & Palshof, T. 1984. The effect of tamoxifen on bone mineral content in premenopausal women with breast cancer. Cancer 53, 853–857.Google Scholar
Gulino, A., Barrera, G., Vacca, A., Farina, A., Ferretti, C., Screpanti, I., Dianzani, M. U. & Frati, L. 1986. Calmodulin antagonism and growth-inhibiting activity of triphenylethylene anti-oestrogens in MCF-7 human breast cancer cells. Cancer Research 46, 6274–8.Google Scholar
Haggie, J. A., Sellwood, R. A., Howell, A., Birch, J. M. & Schor, S. L. 1987. Fibroblasts of patients with hereditary breast cancer show fetal-like behaviour in vitro. Lancet (i), 1455–1457.Google Scholar
Harris, A. L. & Neal, D. E. 1987. Epidermal growth factor and its receptor in human breast cancer. In Growth factors and oncogenes in breast cancer, ed. Sluyser, M., Chap 4, pp. 60–90. Chichester, England: Ellis Horwood Ltd.Google Scholar
Horgan, K., Jones, D. L. & Mansel, R. E. 1987. Mitogenicity of human fibroblasts in vivo for human breast cancer cells. British Journal of Surgery 74, 227–229.Google Scholar
Kaplan, F. S., Fallon, M. D., Boden, S. D., Schmidt, R., Senior, M. & Haddad, J. G. 1988. Estrogen receptors in bone in a patient with polyostotic fibrous dysplasia (McCune-Albright syndrome). New England Journal of Medicine 319, 421–425.Google Scholar
Kiel, D. P., Felson, D. T., Anderson, J. J. et al. 1987. Hip fracture and the use of oestrogens in postmenopausal women (Framingham study). New England Journal of Medicine 317, 1169–74.CrossRefGoogle ScholarPubMed
Knabbe, C., Lippman, M. E. & Wakefield, L. M. 1987. Evidence that TGF-beta is a hormonally regulated growth factor in human breast cancer cells. Cell 48, 417–428.Google Scholar
Komm, B. S., Terpening, C. M., Benz, D. J., Greame, K. A., Gallegos, A., Korc, M., Greene, G. L., O'Malley, B. W. & Haussler, M. R. 1988. Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. Science 241, 81–84.Google Scholar
Murphy, P., Alexander, P., Senior, P. V., Fleming, J., Kirkham, N., Taylor, I. 1988. Mechanisms of organ selective tumour growth by bloodborne cancer cells. British Journal of Cancer 57, 19.CrossRefGoogle ScholarPubMed
NATO 1988. Controlled trial of tamoxifen as single adjuvant agent in the management of early breast cancer. British Journal of Cancer 57, 608–611.CrossRefGoogle Scholar
Paganini-Hill, A., Ross, R. K. & Henderson, B. E. 1988. Postmenopausal oestrogen treatment and stroke: a prospective study. British Medical Journal 297, 519–522.Google Scholar
Preece, P. E., Wood, R. A. B., Mackie, C. R. & Cuschieri, A. 1982. Tamoxifen as initial sole treatment of localised breast cancer in elderly women. British Medical Journal 284, 869–70.Google Scholar
Roberts, A. B., Thompson, N. L., Heine, U., Flanders, C. & Sporn, M. B. 1988. Transforming growth factor-beta: possible roles in carcinogenesis. British Journal of Cancer 57, 594–600.CrossRefGoogle ScholarPubMed
Roberts, A. B. & Sporn, M. B. in press. Transforming Growth Factor-Beta. Advances in Cancer Research.Google Scholar
Robertson, J. F. R., Todd, J. H., Elston, C. W. & Blamey, R. W. 1988. Comparison of mastectomy with tamoxifen for treating elderly patients with operable breast cancer. British Medical Journal 297, 511–524.Google Scholar
Robey, P. G., Young, M. F., Flanders, K. C., Roche, N. S., Kondaiah, P., Hari Reddi, A., Termine, J., Sporn, M. B. & Roberts, A. B. 1987. Osteoblasts synthesise and respond to TGF-beta in vitro. Journal of Cell Biology 105, 457.Google Scholar
Rose, D. P., Davis, T. E. 1980. Effects of adjuvant chemohormonal therapy on the ovarian and adrenal function of breast cancer patients. Cancer Research 40, 4043–4047.Google Scholar
Sainsbury, J. R. C., Farndon, J. R., Sherbet, G. V. & Harris, A. L. 1985. Epidermal growth factor receptors and oestrogen receptors in human breast cancer. Lancet (i), 364–366.Google Scholar
Sainsbury, J. R. C., Farndon, J. R., Heedham, G. K., Malcolm, A. J. & Harris, A. L. 1987. Epidermal growth factor receptor status as a predictor of early recurrence of and death from breast cancer. Lancet (i), 1398–1402.Google Scholar
Savvas, M., Brincat, M. & Studd, J. W. W. 1987. Postmenopausal Osteoporosis. British Journal of Hospital Medicine 38, 16.Google Scholar
Scottish Cancer Trials Office 1987. Adjuvant tamoxifen in the management of operable breast cancer: the Scottish trial. Lancet (ii), 171–175.Google Scholar
Skipper, D., Jeffrey, M. J., Cooper, A. J., Taylor, I. & Alexander, P. 1988. Preferential growth of bloodborne cancer cells in colonic anastamoses. British Journal of Cancer 57, 564–568.CrossRefGoogle Scholar
Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A. & McGuire, W. L. 1987. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235, 177–182.CrossRefGoogle ScholarPubMed
Smith, I. 1988. Adjuvant tamoxifen for early breast cancer. British Journal of Cancer 57, 527–528.Google Scholar
Sutherland, R. L., Murphy, L. C., San Foo, M. & Green, M. D. 1980. High affinity anti-oestrogen binding site distinct from the oestrogen receptor. Nature 288, 273–275.Google Scholar
Turner, R. T., Wakley, G. K., Hannon, K. S. & Bell, N. H. 1987. Tamoxifen prevents the skeletal effects of hormone deficiency in rats. Journal of Bone and Mineral Research 2(5), 449–456.CrossRefGoogle ScholarPubMed
Venter, D. J., Tuzi, N. I., Kumar, S. & Gullick, W. J. 1987. Overexpression of the c-erbB-2 oncoprotein in human breast carcinomas: immunohistological assessment correlates with gene amplification. Lancet (ii), 69–72.Google Scholar
Wilson, A. J., Baum, M., Singh, L. & Kangas, L. 1987. Anti-oestrogen therapy of pure mesenchymal tumour. Lancet (i), 508.Google Scholar