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British Journal of Cancer logoLink to British Journal of Cancer
. 1984 Sep;50(3):357–361. doi: 10.1038/bjc.1984.183

Endocrine and clinical consequences of combination tamoxifen-aminoglutethimide in postmenopausal breast cancer.

M Dowsett, A L Harris, I E Smith, S L Jeffcoate
PMCID: PMC1976801  PMID: 6540595

Abstract

By analogy with combination chemotherapy, endocrine agents with different mechanisms of action have been combined in the treatment of patients with advanced breast cancer. The clinical use of tamoxifen+aminoglutethimide+hydrocortisone showed no clinical benefit over the individual use of tamoxifen or aminoglutethimide+hydrocortisone. The endocrine changes occurring in postmenopausal patients as a consequence of their treatment with tamoxifen+aminoglutethimide+hydrocortisone have been examined. Suppression of gonadotrophin and oestrogen levels and increased levels of sex hormone binding globulin were observed. These changes might be expected to be of benefit in the treatment of advanced breast cancer, and do not explain the lack of clinical benefit in combining the treatments. Non-responders to this combination therapy had higher levels of oestrone and dehydroepiandrosterone sulphate whilst on treatment than responders, confirming previous observations in patients treated with aminoglutethimide+hydrocortisone.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson D. C. Sex-hormone-binding globulin. Clin Endocrinol (Oxf) 1974 Jan;3(1):69–96. doi: 10.1111/j.1365-2265.1974.tb03298.x. [DOI] [PubMed] [Google Scholar]
  2. Brodie A. M., Garrett W. M., Hendrickson J. R., Tsai-Morris C. H., Williams J. G. 1. Estrogen antagonists. Aromatase inhibitors, their pharmacology and application. J Steroid Biochem. 1983 Jul;19(1A):53–58. [PubMed] [Google Scholar]
  3. Dowsett M., Harris A. L., Smith I. E., Jeffcoate S. L. Endocrine changes associated with relapse in advanced breast cancer patients on aminoglutethimide therapy. J Clin Endocrinol Metab. 1984 Jan;58(1):99–104. doi: 10.1210/jcem-58-1-99. [DOI] [PubMed] [Google Scholar]
  4. Dowsett M., McGarrick G. E., Harris A. L., Coombes R. C., Smith I. E., Jeffcoate S. L. Prognostic significance of serum prolactin levels in advanced breast cancer. Br J Cancer. 1983 Jun;47(6):763–769. doi: 10.1038/bjc.1983.129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fehér T., Halmy L. Dehydroepiandrosterone and dehydroepiandrosterone sulfate dynamics in obesity. Can J Biochem. 1975 Feb;53(2):215–222. doi: 10.1139/o75-030. [DOI] [PubMed] [Google Scholar]
  6. Ferguson K. M., Hayes M., Jeffcoate S. L. A standardised multicentre procedure for plasma gonadotrophin radioimmunoassay. Ann Clin Biochem. 1982 Sep;19(Pt 5):358–361. doi: 10.1177/000456328201900507. [DOI] [PubMed] [Google Scholar]
  7. Golder M. P., Phillips M. E., Fahmy D. R., Preece P. E., Jones V., Henk J. M., Griffiths K. Plasma hormones in patients with advanced breast cancer treated with tamoxifen. Eur J Cancer. 1976 Sep;12(9):719–723. doi: 10.1016/0014-2964(76)90022-0. [DOI] [PubMed] [Google Scholar]
  8. Harris A. L., Dowsett M., Jeffcoate S. L., Smith I. E. Aminoglutethimide dose and hormone suppression in advanced breast cancer. Eur J Cancer Clin Oncol. 1983 Apr;19(4):493–498. doi: 10.1016/0277-5379(83)90112-8. [DOI] [PubMed] [Google Scholar]
  9. Harris A. L., Dowsett M., Smith I. E., Jeffcoate S. L. Endocrine effects of low dose aminoglutethimide alone in advanced postmenopausal breast cancer. Br J Cancer. 1983 May;47(5):621–627. doi: 10.1038/bjc.1983.100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Harris A. L., Dowsett M., Smith I. E., Jeffcoate S. Aminoglutethimide induced hormone suppression and response to therapy in advanced postmenopausal breast cancer. Br J Cancer. 1983 Oct;48(4):585–594. doi: 10.1038/bjc.1983.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hayward J. L., Carbone P. P., Heusen J. C., Kumaoka S., Segaloff A., Rubens R. D. Assessment of response to therapy in advanced breast cancer. Br J Cancer. 1977 Mar;35(3):292–298. doi: 10.1038/bjc.1977.42. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Iqbal M. J., Johnson M. W. Study of steroid-protein binding by a novel "two-tier" column employing Cibacron Blue F3G-A-Sepharose 4B. I-Sex hormone binding globulin. J Steroid Biochem. 1977 Sep;8(9):977–983. doi: 10.1016/0022-4731(77)90196-0. [DOI] [PubMed] [Google Scholar]
  13. MacDonald P. C., Edman C. D., Hemsell D. L., Porter J. C., Siiteri P. K. Effect of obesity on conversion of plasma androstenedione to estrone in postmenopausal women with and without endometrial cancer. Am J Obstet Gynecol. 1978 Feb 15;130(4):448–455. doi: 10.1016/0002-9378(78)90287-9. [DOI] [PubMed] [Google Scholar]
  14. McGuire W. L. Steroid hormone receptors in breast cancer treatment strategy. Recent Prog Horm Res. 1980;36:135–156. doi: 10.1016/b978-0-12-571136-4.50010-3. [DOI] [PubMed] [Google Scholar]
  15. Reed M. J., Hutton J. D., Baxendale P. M., James V. H., Jacobs H. S., Fisher R. P. The conversion of androstenedione to oestrone and production of oestrone in women with endometrial cancer. J Steroid Biochem. 1979 Jul;11(1C):905–911. doi: 10.1016/0022-4731(79)90028-1. [DOI] [PubMed] [Google Scholar]
  16. Rochefort H., Borgna J. L., Evans E. Cellular and molecular mechanism of action of antiestrogens. J Steroid Biochem. 1983 Jul;19(1A):69–74. [PubMed] [Google Scholar]
  17. Sakai F., Cheix F., Clavel M., Colon J., Mayer M., Pommatau E., Saez S. Increases in steroid binding globulins induced by tamoxifen in patients with carcinoma of the breast. J Endocrinol. 1978 Feb;76(2):219–226. doi: 10.1677/joe.0.0760219. [DOI] [PubMed] [Google Scholar]
  18. Santen R. J., Santner S., Davis B., Veldhuis J., Samojlik E., Ruby E. Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab. 1978 Dec;47(6):1257–1265. doi: 10.1210/jcem-47-6-1257. [DOI] [PubMed] [Google Scholar]
  19. Santen R. J., Worgul T. J., Samojlik E., Boucher A. E., Lipton A., Harvey H. Adequacy of estrogen suppression with aminoglutethimide and hydrocortisone as treatment of human breast cancer: correlation of hormonal data with clinical responses. Cancer Res. 1982 Aug;42(8 Suppl):3397s–3401s. [PubMed] [Google Scholar]
  20. Smith I. E., Harris A. L., Morgan M., Gazet J. C., McKinna J. A. Tamoxifen versus aminoglutethimide versus combined tamoxifen and aminoglutethimide in the treatment of advanced breast carcinoma. Cancer Res. 1982 Aug;42(8 Suppl):3430s–3433s. [PubMed] [Google Scholar]
  21. Smith I. E., Harris A. L., Stuart-Harris R., Ford H. T., Gazet J. C., White H., Harmer C. L., Carr L., McKinna J. A., Morgan M. Combination treatment with tamoxifen and aminoglutethimide in advanced breast cancer. Br Med J (Clin Res Ed) 1983 May 21;286(6378):1615–1616. doi: 10.1136/bmj.286.6378.1615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Vermeulen A. The hormonal activity of the postmenopausal ovary. J Clin Endocrinol Metab. 1976 Feb;42(2):247–253. doi: 10.1210/jcem-42-2-247. [DOI] [PubMed] [Google Scholar]
  23. Wakeling A. E., O'Connor K. M., Newboult E. Comparison of the biological effects of tamoxifen and a new antioestrogen (LY 117018) on the immature rat uterus. J Endocrinol. 1983 Dec;99(3):447–453. doi: 10.1677/joe.0.0990447. [DOI] [PubMed] [Google Scholar]
  24. Willis K. J., London D. R., Ward H. W., Butt W. R., Lynch S. S., Rudd B. T. Recurrent breast cancer treated with the antioestrogen tamoxifen: correlation between hormonal changes and clinical course. Br Med J. 1977 Feb 12;1(6058):425–428. doi: 10.1136/bmj.1.6058.425. [DOI] [PMC free article] [PubMed] [Google Scholar]

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