Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Oct;74(8):1286–1291. doi: 10.1038/bjc.1996.531

Influence of anastrozole (Arimidex), a selective, non-steroidal aromatase inhibitor, on in vivo aromatisation and plasma oestrogen levels in postmenopausal women with breast cancer.

J Geisler 1, N King 1, M Dowsett 1, L Ottestad 1, S Lundgren 1, P Walton 1, P O Kormeset 1, P E Lønning 1
PMCID: PMC2075919  PMID: 8883419

Abstract

The effect of anastrozole ('Arimidex', ZD1033), a new, selective, non-steroidal aromatase inhibitor on in vivo aromatisation and plasma oestrogen levels was evaluated in post-menopausal women with breast cancer. Twelve patients progressing after treatment with tamoxifen were randomised to receive anastrozole 1 mg or 10 mg once daily for a 28 day period in a double-blinded crossover design. In vivo aromatisation and plasma oestrogen levels were determined before commencing treatment and at the end of each 4-week period. Treatment with anastrozole 1 and 10 mg reduced the percentage aromatisation from 2.25% to 0.074% and 0.043% (mean suppression of 96.7% and 98.1% from baseline) and suppressed plasma levels of oestrone, oestradiol and oestrone sulphate by > or = 86.5%, > or = 83.5% and > or = 93.5% respectively, irrespective of dose. Notably, several patients had their oestrone and oestradiol values suppressed beneath the sensitivity limit of the assays. In conclusion, anastrozole was found to be highly effective in inhibiting in vivo aromatisation with no difference in efficacy between the two drug doses. Contrary to previous studies on other aromatase inhibitors, this study revealed an internal consistency between the percentage aromatase inhibition and suppression of plasma oestrone sulphate.

Full text

PDF
1289

Selected References

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

  1. Cash R., Brough A. J., Cohen M. N., Satoh P. S. Aminoglutethimide (Elipten-Ciba) as an inhibitor of adrenal steroidogenesis: mechanism of action and therapeutic trial. J Clin Endocrinol Metab. 1967 Sep;27(9):1239–1248. doi: 10.1210/jcem-27-9-1239. [DOI] [PubMed] [Google Scholar]
  2. Coombes R. C., Goss P., Dowsett M., Gazet J. C., Brodie A. 4-Hydroxyandrostenedione in treatment of postmenopausal patients with advanced breast cancer. Lancet. 1984 Dec 1;2(8414):1237–1239. doi: 10.1016/s0140-6736(84)92795-8. [DOI] [PubMed] [Google Scholar]
  3. Demers L. M., Lipton A., Harvey H. A., Kambic K. B., Grossberg H., Brady C., Santen R. J. The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer. J Steroid Biochem Mol Biol. 1993 Mar;44(4-6):687–691. doi: 10.1016/0960-0760(93)90283-3. [DOI] [PubMed] [Google Scholar]
  4. Dowsett M., Cunningham D. C., Stein R. C., Evans S., Dehennin L., Hedley A., Coombes R. C. Dose-related endocrine effects and pharmacokinetics of oral and intramuscular 4-hydroxyandrostenedione in postmenopausal breast cancer patients. Cancer Res. 1989 Mar 1;49(5):1306–1312. [PubMed] [Google Scholar]
  5. Dowsett M., Goss P. E., Powles T. J., Hutchinson G., Brodie A. M., Jeffcoate S. L., Coombes R. C. Use of the aromatase inhibitor 4-hydroxyandrostenedione in postmenopausal breast cancer: optimization of therapeutic dose and route. Cancer Res. 1987 Apr 1;47(7):1957–1961. [PubMed] [Google Scholar]
  6. Dowsett M., Jones A., Johnston S. R., Jacobs S., Trunet P., Smith I. E. In vivo measurement of aromatase inhibition by letrozole (CGS 20267) in postmenopausal patients with breast cancer. Clin Cancer Res. 1995 Dec;1(12):1511–1515. [PubMed] [Google Scholar]
  7. Dowsett M., Stein R. C., Mehta A., Coombes R. C. Potency and selectivity of the non-steroidal aromatase inhibitor CGS 16949A in postmenopausal breast cancer patients. Clin Endocrinol (Oxf) 1990 May;32(5):623–634. doi: 10.1111/j.1365-2265.1990.tb00906.x. [DOI] [PubMed] [Google Scholar]
  8. Evans T. R., Di Salle E., Ornati G., Lassus M., Benedetti M. S., Pianezzola E., Coombes R. C. Phase I and endocrine study of exemestane (FCE 24304), a new aromatase inhibitor, in postmenopausal women. Cancer Res. 1992 Nov 1;52(21):5933–5939. [PubMed] [Google Scholar]
  9. Fotsis T., Adlercreutz H. The multicomponent analysis of estrogens in urine by ion exchange chromatography and GC-MS--I. Quantitation of estrogens after initial hydrolysis of conjugates. J Steroid Biochem. 1987 Aug;28(2):203–213. doi: 10.1016/0022-4731(87)90379-7. [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. Iveson T. J., Smith I. E., Ahern J., Smithers D. A., Trunet P. F., Dowsett M. Phase I study of the oral nonsteroidal aromatase inhibitor CGS 20267 in healthy postmenopausal women. J Clin Endocrinol Metab. 1993 Aug;77(2):324–331. doi: 10.1210/jcem.77.2.8345035. [DOI] [PubMed] [Google Scholar]
  12. Jacobs S., Lønning P. E., Haynes B., Griggs L., Dowsett M. Measurement of aromatisation by a urine technique suitable for the evaluation of aromatase inhibitors in vivo. J Enzyme Inhib. 1991;4(4):315–325. doi: 10.3109/14756369109030396. [DOI] [PubMed] [Google Scholar]
  13. Johnston S. R., Smith I. E., Doody D., Jacobs S., Robertshaw H., Dowsett M. Clinical and endocrine effects of the oral aromatase inhibitor vorozole in postmenopausal patients with advanced breast cancer. Cancer Res. 1994 Nov 15;54(22):5875–5881. [PubMed] [Google Scholar]
  14. Jones A. L., MacNeill F., Jacobs S., Lonning P. E., Dowsett M., Powles T. J. The influence of intramuscular 4-hydroxyandrostenedione on peripheral aromatisation in breast cancer patients. Eur J Cancer. 1992;28A(10):1712–1716. doi: 10.1016/0959-8049(92)90074-c. [DOI] [PubMed] [Google Scholar]
  15. Lipton A., Demers L. M., Harvey H. A., Kambic K. B., Grossberg H., Brady C., Adlercruetz H., Trunet P. F., Santen R. J. Letrozole (CGS 20267). A phase I study of a new potent oral aromatase inhibitor of breast cancer. Cancer. 1995 Apr 15;75(8):2132–2138. doi: 10.1002/1097-0142(19950415)75:8<2132::aid-cncr2820750816>3.0.co;2-u. [DOI] [PubMed] [Google Scholar]
  16. Lønning P. E., Dowsett M., Powles T. J. Postmenopausal estrogen synthesis and metabolism: alterations caused by aromatase inhibitors used for the treatment of breast cancer. J Steroid Biochem. 1990 Mar;35(3-4):355–366. doi: 10.1016/0022-4731(90)90241-j. [DOI] [PubMed] [Google Scholar]
  17. Lønning P. E., Ekse D. A sensitive assay for measurement of plasma estrone sulphate in patients on treatment with aromatase inhibitors. J Steroid Biochem Mol Biol. 1995 Dec;55(3-4):409–412. doi: 10.1016/0960-0760(95)00180-8. [DOI] [PubMed] [Google Scholar]
  18. Lønning P. E., Helle S. I., Johannessen D. C., Adlercreutz H., Lien E. A., Tally M., Ekse D., Fotsis T., Anker G. B., Hall K. Relations between sex hormones, sex hormone binding globulin, insulin-like growth factor-I and insulin-like growth factor binding protein-1 in post-menopausal breast cancer patients. Clin Endocrinol (Oxf) 1995 Jan;42(1):23–30. doi: 10.1111/j.1365-2265.1995.tb02594.x. [DOI] [PubMed] [Google Scholar]
  19. Lønning P. E., 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. 1991 May;63(5):789–793. doi: 10.1038/bjc.1991.175. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lønning P. E., Kvinnsland S. Mechanisms of action of aminoglutethimide as endocrine therapy of breast cancer. Drugs. 1988 Jun;35(6):685–710. doi: 10.2165/00003495-198835060-00005. [DOI] [PubMed] [Google Scholar]
  21. MacNeill F. A., Jones A. L., Jacobs S., Lønning P. E., Powles T. J., Dowsett M. The influence of aminoglutethimide and its analogue rogletimide on peripheral aromatisation in breast cancer. Br J Cancer. 1992 Oct;66(4):692–697. doi: 10.1038/bjc.1992.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Masamura S., Adlercreutz H., Harvey H., Lipton A., Demers L. M., Santen R. J., Santner S. J. Aromatase inhibitor development for treatment of breast cancer. Breast Cancer Res Treat. 1995;33(1):19–26. doi: 10.1007/BF00666067. [DOI] [PubMed] [Google Scholar]
  23. Plourde P. V., Dyroff M., Dowsett M., Demers L., Yates R., Webster A. ARIMIDEX: a new oral, once-a-day aromatase inhibitor. J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):175–179. doi: 10.1016/0960-0760(95)00045-2. [DOI] [PubMed] [Google Scholar]
  24. Plourde P. V., Dyroff M., Dukes M. Arimidex: a potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res Treat. 1994;30(1):103–111. doi: 10.1007/BF00682745. [DOI] [PubMed] [Google Scholar]
  25. Reed M. J., Lai L. C., Owen A. M., Singh A., Coldham N. G., Purohit A., Ghilchik M. W., Shaikh N. A., James V. H. Effect of treatment with 4-hydroxyandrostenedione on the peripheral conversion of androstenedione to estrone and in vitro tumor aromatase activity in postmenopausal women with breast cancer. Cancer Res. 1990 Jan 1;50(1):193–196. [PubMed] [Google Scholar]
  26. Santen R. J., Demers L. M., Adlercreutz H., Harvey H., Santner S., Sanders S., Lipton A. Inhibition of aromatase with CGS 16949A in postmenopausal women. J Clin Endocrinol Metab. 1989 Jan;68(1):99–106. doi: 10.1210/jcem-68-1-99. [DOI] [PubMed] [Google Scholar]
  27. Santen R. J., Santner S. J., Tilsen-Mallett N., Rosen H. R., Samojlik E., Veldhuis J. D. In vivo and in vitro pharmacological studies of aminoglutethimide as an aromatase inhibitor. Cancer Res. 1982 Aug;42(8 Suppl):3353s–3359s. [PubMed] [Google Scholar]
  28. 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]
  29. Vermeulen A., Paridaens R., Heuson J. C. Effects of aminoglutethimide on adrenal steroid secretion. Clin Endocrinol (Oxf) 1983 Dec;19(6):673–682. doi: 10.1111/j.1365-2265.1983.tb00044.x. [DOI] [PubMed] [Google Scholar]
  30. van der Wall E., Donker T. H., de Frankrijker E., Nortier H. W., Thijssen J. H., Blankenstein M. A. Inhibition of the in vivo conversion of androstenedione to estrone by the aromatase inhibitor vorozole in healthy postmenopausal women. Cancer Res. 1993 Oct 1;53(19):4563–4566. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES