Skip to main content
SpringerLink
Log in

Influence of aminoglutethimide on plasma oestrogen levels in breast cancer patients on 4-hydroxyandrostenedione treatment

  • Report
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

The clinical and biochemical effects of combined treatment with the two aromatase inhibitors aminoglutethimide and 4-hydroxyandrostenedione were evaluated in 10 patients suffering from advanced breast cancer. All patients had become resistant to treatment with one of the drugs before having combined treatment. Seven patients progressing on 4-hydroxyandrostenedione who had aminoglutethimide added to their treatment and achieved a further suppression of plasma oestradiol by a mean of 40.0% (p<0.05). Plasma oestrone was suppressed by a mean of 40.6% (p<0.025) and plasma oestrone sulphate was suppressed by a mean of 63.6% (p<0.025). Two of the patients, neither of whom had responded to 4-hydroxyandrostenedione alone, experienced objective tumour regression when aminoglutethimide was given in concert. Three patients progressing on aminoglutethimide who had 4-hydroxyandrostenedione added showed no further suppression of their plasma oestrogen levels, and no tumour regression was observed. These findings suggest a dose-response relationship between plasma oestrogen suppression at low postmenopausal levels and objective tumour response in breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Santen RJ, Manni A, Harvey H, Redmond C: Endocrine treatment of breast cancer in women. Endocrine Reviews 11: 221–265, 1990

    PubMed  Google Scholar 

  2. Lønning PE, Kvinnsland S: Mechanisms of action of aminoglutethimide as endocrine therapy of breast cancer. Drugs 35: 685–710, 1988

    PubMed  Google Scholar 

  3. Goss PE, Powles TJ, Dowsett M, Hutchinson G, Brodie AMH: Treatment of advanced postmenopausal breast cancer with an aromatase inhibitor, 4-hydroxyandrostenedione: Phase II report. Cancer Res 46: 4823–4826, 1986

    Google Scholar 

  4. Haynes BP, Jarman M, Dowsett M, Mehta A, Lønning PE: Pharmacokinetics and pharmacodynamics of the aromatase inhibitor 3-ethyl-3(4-pyridyl)piperidine-2,6-dione in patients with postmenopausal breast cancer. Cancer Chemother Pharmacol 27: 367–372, 1991

    PubMed  Google Scholar 

  5. Stein RC, Dowsett M, Davenport J, Hedley A, Ford HT: Preliminary study of the treatment of advanced breast cancer in postmenopausal women with the aromatase inhibitor CGS 16949A. Cancer Res 50: 1381–1385, 1990

    PubMed  Google Scholar 

  6. Barone RM, Shamonki IM, Siiteri PK, Judd HL: Inhibition of peripheral aromatization of androstenedione to estrone in postmenopausal women with breast cancer using Δ1-testolactone. J Clin Endocrinol Metab 49: 672–676, 1979

    PubMed  Google Scholar 

  7. Dowsett M, Santner SJ, Santen RJ, Jeffcoate SL, Smith IE: Effective inhibition by low-dose aminoglutethimide of peripheral aromatisation in postmenopausal breast cancer patients. Br J Cancer 52: 31–35, 1985

    PubMed  Google Scholar 

  8. Lønning PE, Jacobs S, Jones A, Haynes B, Powles T. Dowsett M: The influence of CGS.16949A on peripheral aromatisation in breast cancer patients. Br J Cancer 63: 789–793, 1991

    PubMed  Google Scholar 

  9. Reed MJ, Lai LC, Owen AM, Singh A, Coldham NG: Effect of treatment with 4-hydroxyandrostenedione on the pheripheral conversion of androstenedione to estrone andin vitro tumor aromatase activity in postmenopausal women with breast cancer. Cancer Res 50: 193–196, 1990

    PubMed  Google Scholar 

  10. Santen RJ, Santner S, Davis B, Veldhuis J, Samojlik E: Aminoglutethimide inhibits extra-glandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 47: 1257–1265, 1978

    PubMed  Google Scholar 

  11. Dowsett M, Cunningham DC, Stein RC, Evans S, Dehennin L, Hedley A, Coombes RC: Dose-related endocrine effects and pharmacokinetics of oral and intramuscular 4-hydroxyandrostenedione in postmenopausal breast cancer patients. Cancer Res 49: 1306–1312, 1989

    PubMed  Google Scholar 

  12. Santen RJ, Worgul TJ, Lipton A, Harvey H, Boucher A, Samojlik E, Wells SA: Aminoglutethimide as treatment of postmenopausal women with advanced breast carcinoma. Ann Intern Med 96: 94–101, 1982

    PubMed  Google Scholar 

  13. Vermeulen A, Paridaens R, Heuson JC: Effects of aminoglutethimide on adrenal steroid secretion. Clin Endocr 19: 673–682, 1983

    PubMed  Google Scholar 

  14. Murray R, Pitt P: Low-dose aminoglutethimide without steroid replacement in the treatment of postmenopausal women with advanced breast cancer. Eur J Cancer Clin Oncol 21: 19–22, 1985

    PubMed  Google Scholar 

  15. Dowsett M, Harris AL, Stuart-Harris R, Hill M, Cantwell BMJ, Smith IE, Jeffcoate SL: A comparison of the endocrine effects of low dose aminoglutethimide with and without hydrocortisone in postmenopausal breast cancer patients. Br J Cancer 52: 525–529, 1985

    PubMed  Google Scholar 

  16. Vermeulen A, Paridaens R, Heuson JC: Effects of aminoglutethimide on adrenal steroid secretion. Clin Endocrinol 19: 673–682, 1983

    Google Scholar 

  17. Lønning PE, Johannessen DC, Thorsen T: Alterations in the production rate and the metabolism of oestrone and oestrone sulphate in breast cancer patients treated with aminoglutethimide. Br J Cancer 60: 107–111, 1989

    PubMed  Google Scholar 

  18. Santner SJ, Feil PD, Santen RJ:In situ estrogen production via the estrone sulfatase pathway in breast tumours: relative importance versus the aromatase pathway. J Clin Endocrinol Metab 59: 29–33, 1984

    PubMed  Google Scholar 

  19. Pasqualini JR, Gelly C, Nguyen B-L, Vella C: Importance of estrogen sulfates in breast cancer. J Steroid Biochem 34: 155–163, 1989

    PubMed  Google Scholar 

  20. Brodie AMH, Wing LY, Goss P, Dowsett M, Coombes RC: Aromatase inhibitors and the treatment of breast cancer. J Steroid Biochem 24: 91–97, 1986

    PubMed  Google Scholar 

  21. Dowsett M, Goss PE, Powles TJ, Hutchinson G, Brodie AMH, Jeffcoate SL, Coombes RC: Use of the aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: optimization of therapeutic dose and route. Cancer Res 47: 1957–1961, 1987

    Google Scholar 

  22. Cunningham D, Powles TJ, Dowsett M, Hutchison G, Brodie AMH, Ford HT, Gazet J-C, Coombes RC: Oral 4-hydroxyandrostenedione, a new endocrine treatment for disseminated breast cancer. Cancer Chemother Pharmacol 20: 253–255, 1987

    PubMed  Google Scholar 

  23. Stein RC, Dowsett M, Hedley A, Davenport J, Gazet J-C, Ford HT, Coombes RC: Treatment of advanced breast cancer in postmenopausal women with 4-hydroxyandrostenedione. Cancer Chemother Pharmacol 26: 75–78, 1990

    PubMed  Google Scholar 

  24. Höffken K, Jonat W, Possinger K, Kölbel M, Kunz T, Wagner H, Becher R, Callies R, Friederich P, Willmanns W, Maas H, Schmidt CG: Aromatase inhibition with 4-hydroxyandrostenedione in the treatment of postmenopausal patients with advanced breast cancer: a phase II study. J Clin Oncol 8: 875–880, 1990

    PubMed  Google Scholar 

  25. Hayward JL, Rubens RD, Carbone PP, Heuson J-C, Kumaoka S, Segaloff A: Assessment of response to therapy in advanced breast cancer. Brit J Cancer 35: 292–298, 1977

    PubMed  Google Scholar 

  26. Lønning PE, Johannessen DC, Thorsen T, Ekse D: Effects of aminoglutethimide on plasma estrone sulfate not caused by aromatase inhibition. J Steroid Biochem 33: 541–545, 1989

    PubMed  Google Scholar 

  27. Santner SJ, Rosen H, Osawa Y, Santen RJ: Additive effects of aminoglutethimide testololactone, and 4-hydroxyandrostenedione as inhibitors of aromatase. J Steroid Biochem 20: 1239–1242, 1983

    Google Scholar 

  28. Samojlik E, Santen RJ, Worgul TJ: Plasma estrone-sulfate assessment of reduced estrogen production during treatment of metastatic breast carcinoma. Steroids 39: 497–507, 1982

    PubMed  Google Scholar 

  29. Santen RJ, Demers LM, Adlercreutz H, Harvey H, Santner S, Sanders S, Lipton A: Inhibition of aromatase with CGS 16949A in postmenopausal women. J Clin Endocrinol Metab 68: 99–106, 1989

    PubMed  Google Scholar 

  30. Lønning PE, Dowsett M, Powles TJ: Postmenopausal estrogen synthesis and metabolism: alteration caused by aromatase inhibitors used for the treatment of breast cancer. J Steroid Biochem 35: 355–366, 1990

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Oncology, Haukeland University Hospital, 5021, Bergen, Norway

    P. E. Lønning, D. Ekse & D. C. Johannessen

  2. Department of Academic Biochemistry, The Royal Marsden Hospital, Fulham Road, SW3 6JJ, London, UK

    M. Dowsett & S. Jacobs

  3. Department of Medicine, The Royal Marsden Hospital, Surrey, UK

    A. Jones, F. McNeil & T. J. Powles

Authors
  1. P. E. Lønning
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Dowsett
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Jones
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Ekse
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. Jacobs
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. F. McNeil
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. D. C. Johannessen
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T. J. Powles
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lønning, P.E., Dowsett, M., Jones, A. et al. Influence of aminoglutethimide on plasma oestrogen levels in breast cancer patients on 4-hydroxyandrostenedione treatment. Breast Cancer Res Tr 23, 57–62 (1992). https://doi.org/10.1007/BF01831476

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01831476

Key words

Search

Navigation