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LH-RH Agonists in the Treatment of Metastatic Breast Cancer: Ten Years’ Experience

  • J. G. M. Klijn
Part of the Recent Results in Cancer Research book series (RECENTCANCER, volume 124)

Abstract

Different steroid and peptide hormones, growth factors and other tropic substances are involved in the growth regulation of breast cancer cells. Estrogens play an especially important role. Since the observation of tumor growth remission after surgical castration by Beatson in 1896, various treatment modalities have been developed which suppress gonadal and/or peripheral estrogen production or which antagonize the stimulatory effects of estrogens at the level of the tumor cells [1, 2]. Apart from castration by surgical or radiotherapeutic means, it is possible to suppress pituitary-gonadal function by different kinds of medical treatment. In the past decade it became clinically apparent that luteinizing hormone releasing hormone (LH-RH) analogs are of great interest for suppressing pituitary-gonadal function in the treatment of metastatic breast and prostate cancer, especially because of the absence of serious side effects [3–6].

Keywords

Luteinizing Hormone Release Hormone LHRH Agonist LHRH Analog Medical Castration Plasma Estradiol Level 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Santen RJ, Manni A, Harvey H, Redmond C (1990) Endocrine treatment of breast cancer in women. Endocr Rev 11:221–265PubMedCrossRefGoogle Scholar
  2. 2.
    Dowsett M (1990) Novel approaches for the endocrine therapy of breast cancer. Eur J Cancer 26:989–992PubMedCrossRefGoogle Scholar
  3. 3.
    Klijn JGM, de Jong FH (1982) Treatment with a luteinizing hormone-releasing-hormone analogue (Buserelin) in premenopausal patients with metastatic breast cancer. Lancet 1:1213–1216PubMedCrossRefGoogle Scholar
  4. 4.
    Schally AV, Redding TW, Comaru-Schally AM (1984) Potential use of analogs of luteinizing hormone-releasing hormones in the treatment of hormone-sensitive neoplasms. Cancer Treat Rep 68:281–289PubMedGoogle Scholar
  5. 5.
    Manni A, Santen R, Harvey H, Lipton A, Max D (1986) Treatment of breast cancer with gonadotropin releasing hormone. Endocr Rev 7:89–94PubMedCrossRefGoogle Scholar
  6. 6.
    Waxman J (1987) Gonadotrophin hormone releasing analogues open new doors in cancer treatment. Br Med J 295:1084–1085CrossRefGoogle Scholar
  7. 7.
    Corbin A (1982) From contraception to cancer: a review of the therapeutic applications of LH-RH analogues as antitumor agents. Yale J Biol Med 55:27–47PubMedGoogle Scholar
  8. 8.
    Furr BJA, Nicholson RI (1982) Use of analogues of luteinizing hormone-releasing hormone for the treatment of cancer. J Reprod Fertil 64:529–539PubMedCrossRefGoogle Scholar
  9. 9.
    Sandow J (1983) Clinical applications of LH-RH and its analogues. Clin Endocrinol (Oxf) 18:571–592CrossRefGoogle Scholar
  10. 10.
    Schally AV, Srkalovic G, Szende B, Redding TW, Janaky T, Juhasz A, Korkut E, Cai RZ, Szepeshazik, Radulovic S, Bokser L, Groot K, Serfozo P, Comaru-Schally AM (1990) Antitumor effects of analogs of LH-RH and somatostatin: experimental and clinical studies. J Steroid Biochem Mol Biol 37:1061–1069PubMedCrossRefGoogle Scholar
  11. 11.
    Conn PM, Crowly WF (1991) Gonadotropin-releasing hormone and its analogues. N EnglJ Med 324:93–103CrossRefGoogle Scholar
  12. 12.
    Desombre ER, Johnson ES, White WF (1976) Regression of rat mammary tumors effected by a gonadoliberin analog. Cancer Res 36:3830–3833PubMedGoogle Scholar
  13. 13.
    Danguy A, Legros N, Heuson-Stiennon JA, Pasteeis JL, Atassi G, Heuson JC (1977) Effects of a gonadotropin-releasing hormone (GnRH) analogue (A-43818) on 7,12-di-methylbenz(a)anthracene-induced rat mammary tumours. Histological and endocrine studies. Eur J Cancer 13:1089–1094PubMedGoogle Scholar
  14. 14.
    Klijn JGM, Foekens JA (1989) Extrapituitary actions. In: Vickery BH, Lunenfeld B (eds) GnRH analogues in cancer and human reproduction: basic aspects, vol 1. Kluwer, Dordrecht, pp 71–85Google Scholar
  15. 15.
    Klijn JGM (1988) LH-RH agonists in the treatment of metastatic breast cancer: five years experience. In: Höffken K (ed) LH-RH Agonists in Oncology. Springer, Berlin Heidelberg New York, pp 139–147CrossRefGoogle Scholar
  16. 16.
    Sharoni Y, Bosin E, Münster A, Levy J, Schally AV (1989) Inhibition of growth of human mammary tumor cells by potent antagonists of luteinizing hormone-releasing hormone. Proc Natl Acad Sci USA 86:1648–1651PubMedCrossRefGoogle Scholar
  17. 17.
    Szende B, Srkalovic G, Groot K, Lapis K, Schally AV (1990) Growth inhibition of mouse MXT mammary tumor by the luteinizing hormone-releasing hormone antagonist SB-75. J Natl Cancer Inst 82:513–517PubMedCrossRefGoogle Scholar
  18. 18.
    Klijn JGM (1984) Long-term LH-RH-agonist treatment in metastatic breast cancer as a single treatment and in combination with other additive endocrine treatment. Med Oncol Tumor Pharmacother 1:123–128PubMedGoogle Scholar
  19. 19.
    Klijn JGM, de Jong FH, Blankenstein MA, Docter R, Alexieva-Figusch J, Blonk-van der Wijst J, Lamberts SWJ (1984) Antitumor and endocrine effects of chronic LH-RH agonist (Buserelin) treatment with or without tamoxifen in premenopausal metastatic breast cancer. Breast Cancer Res Treat 4:209–220PubMedCrossRefGoogle Scholar
  20. 20.
    Klijn JGM, de Jong FH (1984) Long-term treatment with the LH-RH-agonist Buserelin (Hoe 766) for metastatic breast cancer in single and combined drug regimen. In: Labrie F, Bélanger A, Dupont A (eds) LH-RH and its analogues, basic and clinical aspects. Excerpta Medica, Amsterdam, pp 425–437Google Scholar
  21. 21.
    Klijn JGM, de Jong FH, Lamberts SWJ, Blankenstein MA (1985) LH-RH-agonist treatment in clinical and experimental human breast cancer. J Steroid Biochem 23:867–873PubMedCrossRefGoogle Scholar
  22. 22.
    Klijn JGM, Henkelman MS, Bakker GH (1987) Treatment of premenopausal women with advanced breast cancer or endometriosis with LH-RH analogues. In: Engelsman E (ed) Proceedings of the symposium on endocrine-related tumours (May 1985, Noord-wijkerhout). Update Siebert, Guildford, pp 160–169Google Scholar
  23. 23.
    Klijn JGM, de Jong FH (1987) Long-term LH-RH-agonist (Buserelin) treatment in metastatic premenopausal breast cancer. In: Klijn JGM, Paridaens R, Foekens JA (eds) Hormonal manipulation of cancer: peptides, growth factors and new (anti)steroidal agents. Raven, New York, pp 343–352 (EORTC Monograph Series, vol 18)Google Scholar
  24. 24.
    Klijn JGM, Foekens JA (1987) Long-term peptide hormone treatment with LH-RH agonists in metastatic breast cancer. In: Santen R, Juhos E (eds) Proceedings of the international symposium on endocrine-dependent breast cancer: critical assessment of recent advances. 14th International Cancer Congress, Budapest (23rd August 1986). Hans Huber, Bern, pp 92–102Google Scholar
  25. 25.
    Nicholson RI, Walker KJ, Turkes A, Dyas J, Plowman PN, Williams M, Blarney RW (1985) Endocrinological and clinical aspects of LH-RH action (ICI-118630) in hormone dependent breast cancer. J Steroid Biochem 23:843–849PubMedCrossRefGoogle Scholar
  26. 26.
    Nicholson RI, Walker KJ, Turkes A, Dyas J, Plowman PN, Williams M, Elston CW, Blarney RW (1987) The British experience with LH-RH agonist Zoladex (ICI-118630) in the treatment of breast cancer. In: Klijn JGM, Paridaens R, Foekens JA (eds) Hormonal manipulation of cancer: peptides, growth factors and new (anti)steroidal agents. Raven, New York, pp 331–343 (EORTC Monograph Series, vol 18)Google Scholar
  27. 27.
    Harvey HA, Lipton A, Max DT (1984) LH-RH-analogs for human mammary carcinoma. In: Vickery BH, Nestor JJ, Hafex ESE (eds) LH-RH and its analogues, contraceptive and clinical application. MTP Press, Lancaster, pp 329–338Google Scholar
  28. 28.
    Harvey HA, Lipton A, Max DT, Pearlman HG, Diaz-Perches R, de la Garza J (1985) Medical castration produced by the GnRH analogue Leuprolide to treat metastatic breast cancer. J Clin Oncol 3:1068–1072PubMedGoogle Scholar
  29. 29.
    Höffken K, Miller B, Fischer P, Becker R, Kurschel E, Scheulen ME, Miller AA, Callies R, Schmidt CG (1986) Buserelin in treatment of premenopausal advanced breast cancer. Eur J Cancer Clin Oncol 22:746CrossRefGoogle Scholar
  30. 30.
    Mathé G, Keiling R, Vovan ML, Gastiaburu J, Prévôt G, Vannetzel JM, Despax R, Jasmin C, Lévi F, Musset M, Machover D, Misset JL (1986) Phase II trial of D-Trp-6-LH-RH in advanced breast cancer. Eur J Cancer Clin Oncol 22:723CrossRefGoogle Scholar
  31. 31.
    Klijn JGM, van Geel AN, Sandow J, de Jong FH (1988) Treatment with high dose LH-RH agonist (buserelin) plus tamoxifen and with buserelin implants in premenopausal patients: an endocrine and pharmacokinetic study. In: Bresciani F, King RJB, Lippman ME, Raynaud JP (eds) Hormones and Cancer 3. Raven, New York, pp 365–368Google Scholar
  32. 32.
    Klijn JGM, van Geel AN, de Jong FH, Sandow J (1990) Endocrine, pharmacokinetic and clinical effects of LH-RH analogue treatment in patients with malignant and benign breast disease. In: Vickery BH, Lunenfeld B (eds) GnRH analogues in cancer and human reproduction: benign and malignant tumours, vol 3. Kluwer, Dordrecht, pp 193–203CrossRefGoogle Scholar
  33. 33.
    Klijn JGM, van Geel B, de Jong FH, Sandow J, Krauss B (1991) The relation between pharmacokinetlcs and endocrine effects of buserelin implants in patients with mastalgia. Clin Endocrinol 34:253–258CrossRefGoogle Scholar
  34. 34.
    Nicholson RI, Walker KJ (1989) Use of LH-RH agonists in the treatment of breast disease. In: Beck JS (ed) Oestrogen and the human breast. The Royal Society of Edinburgh, Edinburgh, pp 271–283Google Scholar
  35. 35.
    Nicholson RI, Walker KJ, Bouzubar N, Wills RJ, Gee JMW, Rushmere NK, Davies P (1990) Estrogen deprivation in breast cancer: clinical, experimental, and biological aspects. Ann New York Acad Sci 595:316–327CrossRefGoogle Scholar
  36. 36.
    Nicholson RI, Walker KJ, McClelland RA, Dixon A, Robertson JFR, Blarney RW (1990) Zoladex plus tamoxifen versus Zoladex alone in pre-and perimenopausal meta-static breast cancer. J Steroid Biochem Mol Biol 37:989–997PubMedCrossRefGoogle Scholar
  37. 37.
    Dixon AR, Robertson JFR, Jackson L, Nicholson RI, Walker KJ, Blarney RW (1990) Goserelin (Zoladex) in premenopausal advanced breast cancer: duration of response and survival. Br J Cancer 62:868–870PubMedCrossRefGoogle Scholar
  38. 38.
    Kaufmann M, Jonat W, Klieberg U, Eiermann W, Jänicke F, Hilfrich J, Kreienberg R, Albrecht M, Weitzel HK, Schmid H, Stunz P, Schachner-Wünschmann E, Bastert G, Maas H, German Zoladex Trial Group (1989) Goserelin, a depot gonadotrophin-releas-ing hormone agonist in the treatment of premenopausal patients with metastatic breast cancer. J Clin Oncol 7:1113–1119PubMedGoogle Scholar
  39. 39.
    Dowsett M, Mehta A, Mansi J, Smith IE (1990) A dose-comparative endocrine-clinical study of leuprolin in premenopausal breast cancer patients. Br J Cancer 62:834–837PubMedCrossRefGoogle Scholar
  40. 40.
    Smith IE (1991) LH-RH analogues in breast cancer: clever, but do we need them? Br J Cancer 63:15–16PubMedCrossRefGoogle Scholar
  41. 41.
    Sandow J, Clayton RH (1983) The disposition, metabolism, kinetics and receptor binding properties of LH-RH and its analogues. In: Briggs M, Corbin A (eds) Progress in hormone-biochemistry and pharmacology, vol 2. Eden, Montreal, pp 63–106Google Scholar
  42. 42.
    Sandow J, Seidel HR, Krauss B, Jerabek-Sandow G (1987) Pharmacokinetic of LH-RH agonists in different delivery systems and the relation to endocrine function. In: Klijn JGM, Paridaens R, Foekens JA (eds) Hormonal manipulation of cancer: peptides, growth factors and new (anti)steroidal agents. Raven, New York, pp 203–212 (EORTC Monograph Series, vol. 18)Google Scholar
  43. 43.
    Sandow J, Fraser HM, Seidel H, Krauss B, Jerabek-Sandow G, von Rechenberg W (1987) Buserelin: pharmacokinetics, metabolism and mechanisms of action. Br J Clin Pract 41 [Suppl 48]:6–13Google Scholar
  44. 44.
    Tharandt L, Schulte H, Benker G, Hackenberg K, Reinwein D (1979) Binding of luteinizing hormone-releasing hormone to human serum proteins — influence of a chronic treatment with a more potent analogue of LH-RH. Horm Metab Res 11:391PubMedCrossRefGoogle Scholar
  45. 45.
    Manni A, Pearson OH (1980) Antiestrogen-induced remissions in premenopausal women with stage IV breast cancer: effects on ovarian function. Cancer Treat Rep 64:779–785PubMedGoogle Scholar
  46. 46.
    Klijn JGM, van Maarschalkerweerd MW, Sandow J, de Jong FH (1988) Treatment with LH-RH agonist (buserelin) implants once every 8 weeks in combination with tamoxifen for premenopausal metastatic breast cancer. Cancer Chemother Pharmacol 23 [Suppl. C47] (abstract 185)Google Scholar
  47. 47.
    Dowsett M, Cantwell B, Anshumala L, Jeffcoate SL, Harris AL (1988) Suppression of postmenopausal ovarian steroidogenesis with the luteinizing hormone-releasing hormone agonist goserelin. J Clin Endocrinol Metab 66:672–677PubMedCrossRefGoogle Scholar
  48. 48.
    Harris AL, Carmichael J, Cantwell BMJ, Dowsett M (1989) Zoladex: endocrine and therapeutic effects in postmenopausal breast cancer. Br J Cancer 59:97–99PubMedCrossRefGoogle Scholar
  49. 49.
    Williamson K, Robertson JFR, Ellis IO, Elston CW, Nicholson RI, Blarney RW (1988) Effect of LH-RH agonist Zoladex on ovarian histology. Br J Surg 75:595–596PubMedCrossRefGoogle Scholar
  50. 50.
    Bakker GH, Setyono-Han B, Portengen H, de Jong FH, Foekens JA, Klijn JGM (1989) Endocrine and antitumor effects of combined treatment with an antiprogestin and anti-estrogen or luteinizing hormone-releasing hormone agonist in female rats bearing mammary tumors. Endocrinology 125:1593–1598PubMedCrossRefGoogle Scholar
  51. 51.
    Waxman JH, Harland SJ, Coombes RC, Wrigley PFM, Malpas JS, Powles T, Lister TA (1985) The treatment of postmenopausal women with advanced breast cancer with buserelin. Cancer Chemother Pharmacol 15:171–173PubMedCrossRefGoogle Scholar
  52. 52.
    Plowman PN, Nicholson RI, Walker KJ (1986) Remissions of postmenopausal breast cancer during treatment with the luteinizing hormone-releasing hormone agonist ICI 118630. Br J Cancer 54:903–909PubMedCrossRefGoogle Scholar
  53. 53.
    Crighton IL, Dowsett M, Lal A, Man A, Smith IE (1989) Use of luteinizing hormone-releasing hormone agonist (leuprorelin) in advanced postmenopausal breast cancer: clinical and endocrine effects. Br J Cancer 60:644–648PubMedCrossRefGoogle Scholar
  54. 54.
    Schwartz L, Guiochet N, Keiling R (1988) Two partial remissions induced by an LH-RH analogue in two postmenopausal women with metastatic breast cancer. Cancer 62:2498–2500PubMedCrossRefGoogle Scholar
  55. 55.
    Wander HE, Kleeberg UR, Schachner-Wünschmann E, Nagel GA (1987) A long-acting depot preparation of a synthetic GnRH agonist (Zoladex) in the treatment of pre-and postmenopausal advanced breast cancer. J Steroid Biochem 28 [Suppl. 104 S] (abstract C-017)Google Scholar
  56. 56.
    Kaufmann M (1987) Treatment of advanced breast cancer with a long-acting depot preparation of a synthetic GnRH-agonist (Zoladex) in premenopausal patients. Abstract book of the 4th EORTC breast cancer working conference. (Abstract F 1.8)Google Scholar
  57. 57.
    Bianco AR, Calabresi F, Fiorentino M, Fosser V, Lenti R, Rosso R, Sismondi PG (1989) Gn-RH analogue goserelin (Zoladex) in the treatment of pre-and perimenopausal women with metastatic breast cancer. 5th European conference on clinical oncology (London, September 3-7)Google Scholar
  58. 58.
    Höffken K, Weinhardt O, Wandl U, Gimzel K, Overkamp F, Scheulen ME, Calies R, Sandow J, Schmidt CG (1989) Depot buserelin in premenopausal breast cancer: a pharmacokinetic and endocrinological phase I-II study. 5th European conference on clinical oncology (London, September 3-7)Google Scholar
  59. 59.
    Nomura (1989) Zoladex in the treatment of breast cancer. International symposium on current controversies in breast cancer (Cambridge, September 8-9)Google Scholar
  60. 60.
    Klijn JGM (1991) Future trials of endocrine therapy in the management of advanced breast cancer. In: Howell A (ed) Current controversies in the treatment of cancer, vol. 1: the role of antihormones. Parthenon, Carnforth, pp 51–65Google Scholar
  61. 61.
    Planting AST, Alexieva-Figusch J, Blonk-van der Wijst J, van Putten WLJ (1985) Tamox-ifen therapy in premenopausal women with metastatic breast cancer. Cancer Treat Rep 69:363–368PubMedGoogle Scholar
  62. 62.
    Buchanan RB, Blarney RW, Durrant KR, Howell A, Paterson AG, Preece PE, Smith DC, Williams CJ, Wilson RG (1986) A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer. J Clin Oncol 4:1326–1330PubMedGoogle Scholar
  63. 63.
    Ingle JN, Krook JE, Green SJ, Kubista TP, Everson LK, Ahmann DL, Chang MN, Bisel HF, Windschitl HE, Twito DI, Pfeifle DM (1986) Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer. J Clin Oncol 4:178–185PubMedGoogle Scholar
  64. 64.
    Labrie F, Bélanger A, Dupont A, Emond J, Lacoursiere Y, Monfette G (1984) Combined treatment with LH-RH agonist and pure antiandrogen in advanced carcinoma of prostate. Lancet 11:1090CrossRefGoogle Scholar
  65. 65.
    Klijn JGM, de Voogt HJ, Schröder FH, de Jong FH (1985) Combined treatment with Buserelin and cyproterone acetate in metastatic prostatic carcinoma. Lancet II: 493Google Scholar
  66. 66.
    Schröder FH, Lock TMTW, Chadha DR, Debruyne FMJ, Karthaus HFM, de Jong FH, Klijn JGM, Matroos AW, de Voogt HJ (1987) Metastatic cancer of the prostate managed with buserelin plus cyproterone acetate. J Urol 137:912–919Google Scholar
  67. 67.
    Foekens JA, Henkelman MS, Fukkink JF, Blankenstein MA, Klijn JGM (1986) Combined effects of buserelin, estradiol and tamoxifen on the growth of MCF-7 human breast cancer cells in vitro. Biochem Biophys Res Commun 140:550–556PubMedCrossRefGoogle Scholar
  68. 68.
    Szende B, Serially AV, Srkalovic G, Comaru-Schally AM, Wittliff JL (1989) Adverse effect of tamoxifen with LHRH agonist on oestrogen-receptor-negative mammary carcinoma. Lancet 11:222–223CrossRefGoogle Scholar
  69. 69.
    Stein RC, Dowsett M, Hedley A, Gazet JC, Ford HT, Coombes RC (1990) The clinical and endocrine effects of 4-hydroxyandrostenedione alone and in combination with goserelin in premenopausal women with advanced breast cancer. Br J Cancer 62:679–683PubMedCrossRefGoogle Scholar
  70. 70.
    Szende B, Lapis K, Redding TW, Srkalovic G, Serially AV (1989) Growth inhibition of MXT mammary carcinoma by enhancing programmed cell death (apoptosis) with analogs of LH-RH and somatostatin. Breast Cancer Res Treatm 4:307–314CrossRefGoogle Scholar
  71. 71.
    Bakker GH, Setyono-Han B, Foekens JA, Portengen H, van Putten WLJ, de Jong FH, Lamberts SWJ, Reubi JC, Klijn JGM (1990) The somatostatin analog Sandostatin (SMS 201-995) in treatment of DMBA-induced rat mammary tumors. Breast Cancer Res Treatm 17:23–32CrossRefGoogle Scholar
  72. 72.
    Bakker GH, Setyono-Han B, Henkelman MS, de Jong FH, Lamberts SWJ, van der Schoot P, Klijn JGM (1987) Comparison of the actions of the antiprogestin Mifepristone (RU486), the progestin megestrol acetate, the LHRH analog buserelin, and ovariectomy in treatment of rat mammary tumors. Cancer Treat Rep 71:1021–1027PubMedGoogle Scholar
  73. 73.
    Klijn JGM, van Zijl J, Beex L, Mauriac L, Becquart D, Julien JP, Garcia-Conde J, Piccart M, Jassem J, Burghouts J, Namer M, Mignolet F, Sylvester R, EORTC Breast Cancer Coop Group (1991) LHRH agonist versus LHRH agonist plus tamoxifen versus tamoxifen alone in the treatment of premenopausal breast cancer: a randomized phase III study (EORTC 10881). 5th EORTC breast cancer working conference (Leu-ven, September 3-6)Google Scholar
  74. 74.
    Pike MC, Ross RK, Lobo RA, Key TJA, Potts M, Henderson BE (1989) LHRH agonist and the prevention of breast and ovarian cancer. Br J Cancr 60:142–148CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1992

Authors and Affiliations

  • J. G. M. Klijn
    • 1
  1. 1.Division of Endocrine Oncology, Department of Medical OncologyRotterdam Cancer Institute (Dr. Daniel den Hoed Cancer Center)RotterdamThe Netherlands

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