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A Laboratory Model To Explain the Survival Advantage Observed in Patients Taking Adjuvant Tamoxifen Therapy

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Adjuvant Therapy of Breast Cancer IV

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 127))

Abstract

The nonsteroidal antiestrogen tamoxifen was first described in 1967 [1]. It was initially intended, based on its activity in rodents, for use as an antifertility agent. It was found, however, that tamoxifen actually induces ovulation in subfertile women. The antitumor effects of tamoxifen were more promising. The drug first entered clinical trials in the United Kingdom in 1971 [2] and was approved for use in the United States in 1978. It was initially used as a palliative treatment for advanced breast cancer in postmenopausal, primarily elderly, women. In a randomly selected sample of patients with advanced breast cancer, about 30%–40% have a favorable response to tamoxifen therapy. However, among patients whose primary tumors are estrogen and progesterone receptor positive response rates to tamoxifen are in the range of 70%–80% [3].

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References

  1. Harper MJK, Walpole AL (1967) A new derivative of triphenylethylene: effect on implantation and mode of action in rats. J Reprod Fertil 13:101–119

    Article  PubMed  CAS  Google Scholar 

  2. Cole MP, Jones CJA, Todd IDH (1971) A new antioestrogenic agent in late breast cancer. Br J Cancer 25:270–275

    Article  PubMed  CAS  Google Scholar 

  3. Jordan VC, Wolf MF, Mirecki DM, Whitford DA, Welshons WV (1988) Hormone receptor assays: clinical usefulness in the management of carcinoma of the breast. CRC Crit Rev Clin Lab Sci 26:97–152

    Article  CAS  Google Scholar 

  4. Powles TJ, Hardy JR, Ashley SE, Farrington GM, Cosgrove D, Davey JB, Dowsett M, McKinna A, Nash AG, Sinnett HD, Tillyer CR, Treleven JG (1989) A pilot trial to evaluate the acute toxicity and feasibility of tamoxifen for prevention of breast cancer. Br J Cancer 60:126–131

    Article  PubMed  CAS  Google Scholar 

  5. Powles TJ, Tillyer CR, Jones AJ, Ashley SE, Treleven J, Davey JB, McKenna JA (1990) Prevention of breast cancer with tamoxifen - an update on the Royal Marsden Hospital pilot programme. Eur J Cancer 26:680–684

    Article  PubMed  CAS  Google Scholar 

  6. Early Breast Cancer Trialists’ Collaborative Group (1992) Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy: 133 randomized trials involving 31000 recurrences and 24000 deaths among 75000 women. Lancet 339:1–15, 71–85

    Google Scholar 

  7. Gottardis MM, Jordan VC (1988) Development of tamoxifen-stimulated growth of MCF-7 tumors in athymic mice after long-term antiestrogen administration. Cancer Res 48:5183–5187

    PubMed  CAS  Google Scholar 

  8. Osborne CK, Coronado E, Allred DC, Wiebe V, DeGregorio M (1991) Acquired tamoxifen resistance: correlation with reduced breast tumor levels of tamoxifen and isomerization of trans-4-hydroxytamoxifen. J Natl Cancer Inst 83:1477

    Article  PubMed  CAS  Google Scholar 

  9. Osborne CK, Coronado EB, Robinson JP (1987) Human breast cancer in the athymic nude mouse: cytostatic effects of long term antiestrogen therapy. Eur J Cancer Clin Oncol 23:1189

    Article  PubMed  CAS  Google Scholar 

  10. Lippman ME, Bolan G (1975) Oestrogen-responsive human breast cancer in long-term tissue culture. Nature 256:592

    Article  PubMed  CAS  Google Scholar 

  11. Lippman ME, Bolan G, Huff K (1976) The effects of estrogens and antiestrogens on hormone-responsive breast cancer in long term culture. Cancer Res 36:4595–4601

    PubMed  CAS  Google Scholar 

  12. Shafie SM, Grantham FH (1981) Role of hormones in the growth and regression of human breast cancer cells (MCF-7) transplanted into athymic nude mice. J Natl Cancer Inst 67:51–56

    PubMed  CAS  Google Scholar 

  13. Soule HD, McGrath CM (1980) Estrogen responsive proliferation of clonal human breast cancer cells in athymic mice. Cancer Lett 10:177–189

    Article  PubMed  CAS  Google Scholar 

  14. Huseby RA, Maloney TM, McGrath CM (1984) Evidence for a direct growth- stimulatory effect of estradiol on human MCF-7 cells in vivo. Cancer Res 44:2654–2659

    PubMed  CAS  Google Scholar 

  15. Osborne CK, Hobbs K, Clark GM (1985) Effect of estrogens and antiestrogens on growth of human breast cancer cells in athymic nude mice. Cancer Res 45:584–590

    PubMed  CAS  Google Scholar 

  16. Gottardis MM, Robinson SP, Jordan VC (1988) Estradiol-stimulated growth of MCF-7 tumors implanted in athymic mice: a model to study the tumoristatic action of tamoxifen. J Steroid Biochem 30:311–314

    Article  PubMed  CAS  Google Scholar 

  17. Jordan VC (1975) The anti-tumour effect of tamoxifen in the dimethyl- benzanthracene-induced rat mammary carcinoma model. In: Proceedings of the symposium on the hormonal control of breast cancer, Alderley Park. ICI Pharniaceuticals Division PLC, Macclesfield, pp 11–17

    Google Scholar 

  18. Jordan VC (1976) Antiestrogenic and antitumor properties of tamoxifen in laboratory animals. Cancer Treat Rep 60:1409–1419

    PubMed  CAS  Google Scholar 

  19. Jordan VC (1976) Effect of tamoxifen (ICI 46474) on initiation and growth of DMBA-induced rat mammary carcinoma. Eur J Cancer Clin Oncol 12:419–424

    CAS  Google Scholar 

  20. Jordan VC (1978) Use of the DMBA-induced rat mammary carcinoma system for the evaluation of tamoxifen treatment as a potential adjuvant therapy. Rev Endocrine-related Cancer. Oct Suppl: 49–55

    Google Scholar 

  21. Jordan VC, Lababidi MK, Mirecki DM (1990) Anti-oestrogenic and anti-tumour properties of prolonged tamoxifen therapy in C3H/OUJ mice. Eur J Cancer 26:718–721

    Article  PubMed  CAS  Google Scholar 

  22. Jordan VC, Lababidi MK, Langan-Fahey S (1991) Suppression of mouse mammary tumorigenesis by long-term tamoxifen therapy. J Natl Cancer Inst 83:492–496

    Article  PubMed  CAS  Google Scholar 

  23. Gottardis MM, Jiang S-Y, Jeng M-H, Jordan VC (1989) Inhibition of tamoxifen- stimulated growth of an MCF-7 tumor variant in athymic mice by novel steroidal antiestrogens. Cancer Res 49:4090–4093

    PubMed  CAS  Google Scholar 

  24. Murphy CS, Langan-Fahey S, McCague R, Jordan VC (1990) Structure-function relationships of hydroxylated metabolites of tamoxifen that control the proliferation of estrogen-responsive T47D breast cancer cells in vitro. Mol Pharmacol 38:737–783

    PubMed  CAS  Google Scholar 

  25. McCague R, Kuroda R, LeClerq G, Stoessel S (1986) Synthesis and estrogen receptor binding of 6,7-dihydro-8-phenyl-9-[4-[2-(dimethylamino)ethoxy] phenyl] 5H-benzocyclo-heptene, a nonisomerizable analogue of tamoxifen. X-ray crystallographic studies. J Med Chem 29:2053

    Article  PubMed  CAS  Google Scholar 

  26. Langan-Fahey SM, Tormey DC, Jordan VC (1990) Tamoxifen metabolites in patients on long-term adjuvant tamoxifen therapy for breast cancer. Eur J Cancer 26:883–888

    Article  PubMed  CAS  Google Scholar 

  27. Robinson SP, Langan-Fahey SM, Johnson DA, Jordan VC (1991) Metabolites, pharmacodynamics and pharmacokinetics of tamoxifen in rats and mice compared to the breast cancer patient. Drug Metab Dispos 19:36

    PubMed  CAS  Google Scholar 

  28. Turken S, Siris E, Seldin D, Foster E, Hyman G, Lindsay R (1989) Effects of tamoxifen on spinal density of women with breast cancer. J Natl Cancer Inst 81:1086–1088

    Article  PubMed  CAS  Google Scholar 

  29. Love RR, Newcomb PA, Wiebe DA, Surawicz TS, Jordan VC, Carbone PP, DeMets DL (1990) Lipid and lipoprotein effects of tamoxifen therapy in postmenopausal patients with node negative breast cancer. J Natl Cancer Inst 82:1327–1332

    Article  PubMed  CAS  Google Scholar 

  30. Breast Cancer Trials Committee, Scottish Cancer Trials Office (MRC) (1987) Adjuvant tamoxifen in the management of operable breast cancer: the Scottish Trial. Lancet 2:171–174

    Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, WI, 53792, USA

    D. M. Wolf & V. C. Jordan

Authors
  1. D. M. Wolf
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  2. V. C. Jordan
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Editor information

Editors and Affiliations

  1. Department of Medicine C, Kantonsspital, CH-9007, St. Gallen, Switzerland

    Hans-Jörg Senn  & Beat Thürlimann  & 

  2. Division of Biostatistics, Dana Farber Cancer Institute, 44, Binney Street, Boston, MA, 02115, USA

    Richard D. Gelber Ph.D.

  3. Ospedale Civico, CH-6900, Lugano, Switzerland

    Aron Goldhirsch

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© 1993 Springer-Verlag Berlin · Heidelberg

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Wolf, D.M., Jordan, V.C. (1993). A Laboratory Model To Explain the Survival Advantage Observed in Patients Taking Adjuvant Tamoxifen Therapy. In: Senn, HJ., Gelber, R.D., Goldhirsch, A., Thürlimann, B. (eds) Adjuvant Therapy of Breast Cancer IV. Recent Results in Cancer Research, vol 127. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-84745-5_4

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  • DOI: https://doi.org/10.1007/978-3-642-84745-5_4

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-84747-9

  • Online ISBN: 978-3-642-84745-5

  • eBook Packages: Springer Book Archive

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