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. 1983 Oct;48(4):585–594. doi: 10.1038/bjc.1983.232

Aminoglutethimide induced hormone suppression and response to therapy in advanced postmenopausal breast cancer.

A L Harris, M Dowsett, I E Smith, S Jeffcoate
PMCID: PMC2011499  PMID: 6684948

Abstract

Eighty-one postmenopausal women with advanced breast cancer were studied for the effects of treatment with aminoglutethimide (AG) plus hydrocortisone on peripheral hormones and response to therapy. There were 40 responders (R) and 41 non-responders (NR) at 3 months from the start of treatment. Plasma oestrone concentrations were higher in non-responders at 1 and 2 months after starting AG (Means: NR 106 +/- 50, R 84 +/- 26 pmol l-1, P less than 0.05; highest value NR 121 +/- 51, R 99 +/- 24 pmol l-1, P less than 0.05). High oestrone levels were correlated with bulky liver secondaries, but not with age, tumour-free interval, time from last menstrual period, time from relapse to start of AG or body weight. Non-responders had higher mean prolactin levels on treatment (prolactin less than 500 mIUl-1 in 14/40 NR, 2/35 R, P less than 0.01). High oestrone or prolactin levels were present in 28/41 NR and 6/40 R (P less than 0.001). Dehydroepiandrosterone sulphate suppression did not differ between R and NR. The differences in peripheral endocrine environment in non-responding patients suggest that oestrogen metabolism may differ in non-responding patients and that sub-groups could be selected for rational endocrine therapy.

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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. Atkins H., Bulbrook R. D., Falconer M. A., Hayward J. L., MacLean K. C., Schurr P. H. Urinary steroids in the prediction of response to adrenalectomy or hypophysectomy. A second clinical trial. Lancet. 1968 Dec 14;2(7581):1261–1263. doi: 10.1016/s0140-6736(68)91758-3. [DOI] [PubMed] [Google Scholar]
  3. BULBROOK R. D., GREENWOOD F. C., HADFIELD G. J., SCOWEN E. F. Oophorectomy in breast cancer; an attempt to correlate clinical results with oestrogen production. Br Med J. 1958 Jul 5;2(5087):7–11. doi: 10.1136/bmj.2.5087.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bates T., Rubens R. D., Bulbrook R. D., Goodwin P. R., Wang D. Y., Knight R. K., Hayward J. L. Comparison of pituitary function and clinical response after transphenoidal and transfrontal hypophysectomy for advanced breast cancer. Eur J Cancer. 1976 Oct;12(10):775–782. doi: 10.1016/0014-2964(76)90091-8. [DOI] [PubMed] [Google Scholar]
  5. Borkowski A., L'hermite M., Dor P., Longeval E., Rozencweig M., Muquardt C., Van Cauter E. Steroid sex hormones and prolactin in postmenopausal women with generalized mammary carcinoma during prolonged dexamethasone treatment. J Endocrinol. 1977 May;73(2):235–246. doi: 10.1677/joe.0.0730235. [DOI] [PubMed] [Google Scholar]
  6. Dexter R. N., Fishman L. M., Ney R. L., Liddle G. W. Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: studies of the mechanism of action. J Clin Endocrinol Metab. 1967 Apr;27(4):473–480. doi: 10.1210/jcem-27-4-473. [DOI] [PubMed] [Google Scholar]
  7. Durant J. A., Miller H. Non-specific factors that may influence significance of urinary steroid excretion in breast cancer. Br Med J. 1973 Dec 29;4(5895):767–770. doi: 10.1136/bmj.4.5895.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Gordon G. G., Olivo J., Rafil F., Southren A. L. Conversion of androgens to estrogens in cirrhosis of the liver. J Clin Endocrinol Metab. 1975 Jun;40(6):1018–1026. doi: 10.1210/jcem-40-6-1018. [DOI] [PubMed] [Google Scholar]
  10. Grodin J. M., Siiteri P. K., MacDonald P. C. Source of estrogen production in postmenopausal women. J Clin Endocrinol Metab. 1973 Feb;36(2):207–214. doi: 10.1210/jcem-36-2-207. [DOI] [PubMed] [Google Scholar]
  11. Harris A. L., Dowsett M., Jeffcoate S. L., McKinna J. A., Morgan M., Smith I. E. Endocrine and therapeutic effects of aminoglutethimide in premenopausal patients with breast cancer. J Clin Endocrinol Metab. 1982 Oct;55(4):718–722. doi: 10.1210/jcem-55-4-718. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Harris A. L., Powles T. J., Smith I. E. Aminoglutethimide in the treatment of advanced postmenopausal breast cancer. Cancer Res. 1982 Aug;42(8 Suppl):3405s–3408s. [PubMed] [Google Scholar]
  14. Hawkins R. A., Roberts M. M., Forrest A. P. Oestrogen receptors and breast cancer: current status. Br J Surg. 1980 Mar;67(3):153–169. doi: 10.1002/bjs.1800670302. [DOI] [PubMed] [Google Scholar]
  15. Hemsell D. L., Grodin J. M., Brenner P. F., Siiteri P. K., MacDonald P. C. Plasma precursors of estrogen. II. Correlation of the extent of conversion of plasma androstenedione to estrone with age. J Clin Endocrinol Metab. 1974 Mar;38(3):476–479. doi: 10.1210/jcem-38-3-476. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. JURET P., HAYEM M. [Implantation of intrapituitary radioactive material (Au-198 and Y-90) in metastatic cancers of the breast. Clinical and biological review apropos of 75 cases]. Rev Fr Etud Clin Biol. 1961 Jan;6:19–34. [PubMed] [Google Scholar]
  18. King R. J. Clinical relevance of steroid-receptor measurements in tumours. Cancer Treat Rev. 1975 Dec;2(4):273–293. doi: 10.1016/s0305-7372(75)80009-0. [DOI] [PubMed] [Google Scholar]
  19. Kirschner M. A., Cohen F. B., Ryan C. Androgen-estrogen production rates in postmenopausal women with breast cancer. Cancer Res. 1978 Nov;38(11 Pt 2):4029–4035. [PubMed] [Google Scholar]
  20. Kley H. K., Krüskemper H. L., Keck E. Estrone and estradiol in patients with cirrhosis of the liver: effects of ACTH and dexamethasone. J Clin Endocrinol Metab. 1976 Sep;43(3):557–560. doi: 10.1210/jcem-43-3-557. [DOI] [PubMed] [Google Scholar]
  21. Lawrence B. V., Lipton A., Harvey H. A., Santen R. J., Wells S. A., Jr, Cox C. E., White D. S., Smart E. K. Influence of estrogen receptor status on response of metastatic breast cancer to aminoglutethimide therapy. Cancer. 1980 Feb 15;45(4):786–791. doi: 10.1002/1097-0142(19800215)45:4<786::aid-cncr2820450429>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  22. McGuire W. L. Hormone receptors: their role in predicting prognosis and response to endocrine therapy. Semin Oncol. 1978 Dec;5(4):428–433. [PubMed] [Google Scholar]
  23. SWYER G. I., LEE A. E., MASTERTON J. P. Oestrogen excretion of patients with breast cancer. Br Med J. 1961 Mar 4;1(5226):617–619. doi: 10.1136/bmj.1.5226.617. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. Santen R. J., Samojlik E., Lipton A., Harvey H., Ruby E. B., Wells S. A., Kendall J. Kinetic, hormonal and clinical studies with aminoglutethimide in breast cancer. Cancer. 1977 Jun;39(6 Suppl):2948–2958. doi: 10.1002/1097-0142(197706)39:6<2948::aid-cncr2820390681>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Santen R. J., Wells S. A., Cohn N., Demers L. M., Misbin R. I., Foltz E. L. Compensatory increase in TSH secretion without effect on prolactin secretion in patients treated with aminoglutethimide. J Clin Endocrinol Metab. 1977 Oct;45(4):739–746. doi: 10.1210/jcem-45-4-739. [DOI] [PubMed] [Google Scholar]
  28. Santen R. J., Worgul T. J., Lipton A., Harvey H., Boucher A., Samojlik E., Wells S. A. Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma. Ann Intern Med. 1982 Jan;96(1):94–101. doi: 10.7326/0003-4819-96-1-94. [DOI] [PubMed] [Google Scholar]
  29. Smith I. E., Fitzharris B. M., McKinna J. A., Fahmy D. R., Nash A. G., Neville A. M., Gazet J. C., Ford H. T., Powles T. J. Aminoglutethimide in treatment of metastatic breast carcinoma. Lancet. 1978 Sep 23;2(8091):646–649. doi: 10.1016/s0140-6736(78)92759-9. [DOI] [PubMed] [Google Scholar]
  30. Smith I. E., Harris A. L., Morgan M., Ford H. T., Gazet J. C., Harmer C. L., White H., Parsons C. A., Villardo A., Walsh G. Tamoxifen versus aminoglutethimide in advanced breast carcinoma: a randomized cross-over trial. Br Med J (Clin Res Ed) 1981 Nov 28;283(6304):1432–1434. doi: 10.1136/bmj.283.6304.1432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tormey D. C., Simon R. M., Lippman M. E., Bull J. M., Myers C. E. Evaluation of tamoxifen dose in advanced breast cancer: a progress report. Cancer Treat Rep. 1976 Oct;60(10):1451–1459. [PubMed] [Google Scholar]
  32. Vermeulen A., Verdonck L. Sex hormone concentrations in post-menopausal women. Clin Endocrinol (Oxf) 1978 Jul;9(1):59–66. doi: 10.1111/j.1365-2265.1978.tb03572.x. [DOI] [PubMed] [Google Scholar]
  33. Victor A., Lundberg P. O., Johansson E. D. Induction of sex hormone binding globulin by phenytoin. Br Med J. 1977 Oct 8;2(6092):934–935. doi: 10.1136/bmj.2.6092.934-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Ward H. W. Combined anti-prolactin and anti-oestrogen therapy for breast carcinoma. Clin Oncol. 1977 Mar;3(1):91–95. [PubMed] [Google Scholar]
  35. 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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