Anabolic-Androgenic Steroids and Experimental Mammary Tumors

Part of the Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology book series (HEP, volume 43)

Abstract

Androgens have been used with success for the treatment of advanced disease states in patients with breast cancer. In a large collaborative study, conducted by the Cooperative Breast Cancer Group (1964), an overall remission rate of 21% was found. The criteria used for defining a remission were quite strict. Another finding from this study was that efficacy was related to menopausal status of the patient, with the highest remission rates found in women who were at least 5 years postmenopausal. This cooperative group clearly established that remission was correlated with prolongation of survival, since the responders to androgen therapy survived on the average twice as long as the patients who failed to respond. The androgens employed in these studies were either testosterone propionate or fluoxymesterone, both potent androgens that produce obvious masculinization (Segaloff et al., 1951). Active programs were initiated to devise compounds having equal or better antitumor effects, but with less androgenic “side-effects.” 1

Keywords

Leukemia Propionate Adenoma Progesterone Prolactin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abe, O., Herranen, A., Dorfman, R.I.: Influence of 2α-methyl-17β-hydroxy-5α-androstan-3-one on incorporation of glycine-2-C14 into proteins of a rat mammary fibroadenoma. A possible bioassay method. Proc. Soc. exp. Biol. (N.Y.) 111, 706–708 (1962).Google Scholar
  2. Bogden, A.E., Esber, H.J., Taylor, D.J., Gray, J.H.: Comparative study on the effects of surgery, chemotherapy, and immunotherapy, alone and in combination, on metastases of the 13762 mammary adenocarcinoma. Cancer Res. 34, 1627–1631 (1974).PubMedGoogle Scholar
  3. Bruchovsky, N., Meakin, J.W.: The metabolism and binding of testosterone in androgen-de-pendent and autonomous transplantable mouse mammary tumors. Cancer Res. 33, 1689–1695 (1973).PubMedGoogle Scholar
  4. Bruchovsky, N., Sutherland, D.J.A., Meakin, J.W., Minesita, T.: Androgen receptors: relationship to growth response and to intracellular androgen transport in nine variant lines of the Shionogi mouse mammary carcinoma. Biochim. biophys. Acta (Amst.) 381, 61–71 (1975).Google Scholar
  5. Burstein, N.A., Carey, R.W.: In vitro assay for human breast cancer hormone responsiveness. Oncology 29, 470–483 (1974).PubMedCrossRefGoogle Scholar
  6. Chayen, J., Altmann, F. P., Bitensky, L., Daly, J.R.: Response of human breast cancer tissue to steroid hormones in vitro. Lancet 1970I, 868–870.Google Scholar
  7. Cooperative Breast Cancer Group: Testosterone propionate therapy of breast cancer. J. Amer. med. Assoc. 188, 1069–1072 (1964).Google Scholar
  8. Dao, T.L., Sunderland, H.: Mammary carcinogenesis by 3-methylcholanthrene. I. Hormonal aspects in tumor induction and growth. J. nat. Cancer Inst. 23, 567–585 (1959).PubMedGoogle Scholar
  9. Dorfman, R.I.: Inhibition of tumor growth by steroids. Methods in Hormone Research, Vol.4, Chap. 7, pp. 165–192. New York: Academic Press 1965.Google Scholar
  10. Dunning, W.F.: Response of some isologously transplanted rat neoplasms to steroids. Ann. N.Y. Acad. Sci. 76, 696–704 (1958).PubMedCrossRefGoogle Scholar
  11. Dunning, W. F.: Steroid-responsive neoplasms in rats and mice. Biological Activities of Steroids in Relation to Cancer, pp.225–256. New York: Academic Press 1960.Google Scholar
  12. Emge, L.A., Murphy, K.M.: Effect of rapidly repeated pregnancies on transplantable mammary rat adenofibromas. Proc. Soc. exp. Biol. (N.Y.) 37, 620–621 (1938).Google Scholar
  13. Fels, E.: Treatment of breast cancer with testosterone propionate. A preliminary report. J. clin. Endocr. 4, 121–125 (1944).CrossRefGoogle Scholar
  14. Finkelstein, M., Geier, A., Horn, H., Levij, I.S., Ever-Hadani, P.: Effect of testosterone and estradiol-17β on synthesis of DNA, RNA and protein in human breast in organ culture. Int. J. Cancer 15, 78–90 (1975).PubMedCrossRefGoogle Scholar
  15. Flax, H., Salih, H., Newton, K.A., Hobbs, J.R.: Are some women’s breast cancers androgen dependent? Lancet 1973I, 1204–1207.Google Scholar
  16. Furth, J., Clifton, K.H.: Screening techniques and problems of hormone-responsive tumors. Ann. N.Y. Acad. Sci. 76, 681–695 (1958).PubMedCrossRefGoogle Scholar
  17. Glenn, E.M., Richardson, S.L., Bowman, B. J.: A method of assay of antitumor activity using a rat mammary fibroadenoma. Endocrinology 64, 379–389 (1959 a).PubMedCrossRefGoogle Scholar
  18. Glenn, E.M., Richardson, S.L., Bowman, B.J., Lyster, S.C.: Steroids and experimental mammary cancer Biological Activities of Steroids in Relation to Cancer, pp. 257–305. New York: Academic Press 1960.Google Scholar
  19. Glenn, E.M., Richardson, S.L., Lyster, S.C., Bowman, B.J.: Inhibition of mammary fibroadenoma of female rats by steroids of the androstane series. Endocrinology 64, 390–399 (1959 b).PubMedCrossRefGoogle Scholar
  20. Griswold, D.P., Green, C.H.: Observations on the hormone sensitivity of 7, 12-dimethylbenz-(a)anthracene-induced mammary tumors in the Sprague-Dawley rat. Cancer. Res. 30, 819–826 (1970).PubMedGoogle Scholar
  21. Griswold, D.P., Laster, W.R., Snow, M.Y., Schabel, F.M., Skipper, H.E.: Experimental evaluation of potential anticancer agents. XII. Quantitative drug response of SA 180, CA 755 and leukemia L 1210 systems to a standard list of active and inactive agents. Cancer Res. 23, Part 2, 271–519 (1963).Google Scholar
  22. Griswold, D.P., Skipper, H.E., Laster, W.R., Jr., Wilcox, W.S., Schabel, F.M., Jr.: Induced mammary carcinoma in the female rat as a drug evaluation system. Cancer Res. 26, 2160–2180 (1966).Google Scholar
  23. Heiman, J., Krehbiel, O.F.: The influence of hormones on breast hyperplasia and tumor growths in white rats. Amer. J. Cancer 27, 450–473 (1936).Google Scholar
  24. Heise, E., Gorlich, M.: Growth and therapy of mammary tumors induced by 7, 12-dimethylbenz-anthracene in rats. Brit. J. Cancer 20, 539–545 (1966).PubMedCrossRefGoogle Scholar
  25. Hilf, R.: Milk-like fluid in a mammary carcinoma: biochemical characterization. Science 155, 826–827 (1967).PubMedCrossRefGoogle Scholar
  26. Hilf, R.: Biochemical studies of experimental mammary tumors as related to human breast cancer. Meth. Cancer Res. 7, 55–114 (1973).Google Scholar
  27. Hilf, R., Freeman, J.J., Johnson, M. M., Stagg, R., Borman, A.: Effects of steroids on three transplantable mammary tumors in the Fischer rat. Cancer Chemother. Rpts. 30, 1–8 (1963 a).Google Scholar
  28. Hilf, R., Freeman, J.J., Michel, I., Borman, A.: Characterization of a transplantable lactating mammary tumor: endocrinological, morphological and biochemical aspects. Cancer Res. 24, 812–824 (1964).PubMedGoogle Scholar
  29. Hilf, R., Goldenberg, H., Michel, I., Carrington, M.J., Bell, C., Gruenstein, M., Meranze, D.R., Shimkin, M.B.: Biochemical characteristics of mammary glands and mammary tumors of rats induced by 3-methylcholanthrene and 7, 12-dimethylbenz(a)anthracene. Cancer Res. 29, 977–988 (1969).PubMedGoogle Scholar
  30. Hilf, R., Johnson, M.M., Breuer, C., Freeman, J.J., Borman, A.: Comparative biochemistry of three transplantable mammary tumors as influenced by steroid therapy. J. nat. Cancer Inst. 31, 541–555 (1963 b).PubMedGoogle Scholar
  31. Hilf, R., Lerner, L.J., Harris, D.N.: The effect of actidione and actinomycin D on androgen-induced biochemical changes in the R 3230 AC mammary carcinoma and uterus of the rat. Trans. N.Y. Acad. Sci. 30, 794–803 (1968a).PubMedGoogle Scholar
  32. Hilf, R., Michel, I., Bell, C.: Biochemical and morphological responses of normal and neoplastic mammary tissue to hormonal treatment. Recent Progr. Hormone Res. 23, 229–295 (1967).PubMedGoogle Scholar
  33. Hilf, R., Michel, I., Bell, C., Freeman, J.J., Borman, A.: Biochemical and morphological properties of a new lactating mammary tumor line in the rat. Cancer Res. 25, 286–299 (1965).PubMedGoogle Scholar
  34. Hilf, R., Segaloff, A., Lerner, L.J.: Influence of hormonal treatment of Fischer rats on the biochemistry of a transplantable dimethylbenz(a)-anthracene-induced mammary carcinoma and its sublines. Cancer Res. 28, 1550–1558 (1968 b).PubMedGoogle Scholar
  35. Hilgar, A.G., Hummel, D.J.: Androgenic and myogenic endocrine bioassay data. Bethesda, Md.: Cancer Chemotherapy National Service Center, 1964.Google Scholar
  36. Hirschberg, E.: Patterns of response of animal tumors to anticancer agents. Cancer Res. 23, Part 2, 521–980 (1963).PubMedGoogle Scholar
  37. Huggins, C., Briziarelli, G., Sutton, H., Jr.: Rapid induction of mammary carcinoma in the rat and the influence of hormones on the tumors. J. exp. Med. 109, 25–42 (1959).PubMedCrossRefGoogle Scholar
  38. Huggins, C., Grand, L.C., Brillantes, F.P.: Mammary cancer induced by a single feeding of polynuclear hydrocarbons, and its suppression. Nature (Lond.) 189, 204–207 (1961a).CrossRefGoogle Scholar
  39. Huggins, C., Mainzer, K.: Hormonal influences on mammary tumors of the rat. II. Retardation of growth of a transplanted fibroadenoma in intact female rats by steroids in the androstane series. J. exp. Med. 105, 485–501 (1957).PubMedCrossRefGoogle Scholar
  40. Huggins, C., Morii, S., Grand, L.C.: Mammary cancer induced by a single dose of polynuclear hydrocarbons: routes of administration. Ann. Surg. 154, 315–318 (1961b).PubMedCrossRefGoogle Scholar
  41. Huggins, C., Torralba, Y., Mainzer, K.: Hormonal influences on mammary tumors of the rat. I. Acceleration of growth of transplanted fibroadenoma in ovariectomized and hypophysec-tomized rats. J. exp. Med. 104, 525–543 (1956).PubMedCrossRefGoogle Scholar
  42. Jensen, E.V., Block, G.E., Smith, S., Kyser, K., Desombre, E.R.: Estrogen receptors and hormone dependency. Estrogen Target Tissues and Neoplasia, pp.23–58. Chicago: University of Chicago Press 1972.Google Scholar
  43. Jungblut, P.W., Hughes, S.F., Gorlich, L., Gowers, U., Wagner, R.K.: Simultaneous occurrence of individual estrogen and androgen receptors in female and male target organs. Hoppe-Seylers Z. Physiol. Chem. 352, 1603–1610 (1971).PubMedCrossRefGoogle Scholar
  44. King, R.J.B., Mainwaring, W.I.P.: Steroid-Cell Interactions. Baltimore: University Park Press 1974.Google Scholar
  45. Korenchevsky, V., Dennison, M.: Histological changes in the organs of rats injected with oestrone alone or simultaneously with oestrone and testicular hormone. J. Path. Bact. 41, 323–337 (1935).CrossRefGoogle Scholar
  46. Lacassagne, A.: Tentatives pour modifier, par la progesterone ou par la testosterone, l’apparition des adenocarcinomes mammaires provoques par l’oestrone chez la souris. C. R. Soc. Biol. (Paris) 126, 385–387 (1937).Google Scholar
  47. Loeser, A.A.: Mammary carcinoma: response to implantation of male hormone and progesterone. Lancet 2, 698–700 (1941).CrossRefGoogle Scholar
  48. Mainwaring, W.I.P., Mangan, F.R.: A study of the androgen receptors in a variety of androgen-sensitive tissues. J. Endocr. 59, 121–139 (1973).PubMedCrossRefGoogle Scholar
  49. Maisin, J., Coolen, M.-L.: Au sujet du pouvoir cancerigene du methylcholanthrene. C. R. Soc. Biol. (Paris) 123, 159–160 (1936).Google Scholar
  50. Matsumoto, K., Kotoh, K., Kosai, H., Minesita, T., Yamaguchi, K.: Subcellular localization of radioactive steroids following administration of testosterone-3H in the androgen dependent mouse tumor, Shionogi carcinoma 115. Steroids 20, 311–320 (1972).PubMedCrossRefGoogle Scholar
  51. Minesita, T., Yamaguchi, K.: An androgen-dependent mouse mammary tumor. Cancer Res. 25, 1168–1175 (1965).PubMedGoogle Scholar
  52. Mohs, F. E.: Effect of estrogen and androgens on growth of mammary fibroma in rats. Proc. Soc. exp. Biol. (N.Y.) 43, 270–272 (1940).Google Scholar
  53. Nathanson, I. T.: Endocrine aspects of human cancer. Recent Progr. Hormone Res. 1, 261–291 (1946).Google Scholar
  54. Nathanson, I. T., Andervont, H.B.: Effect of testosterone propionate on development and growth of mammary carcinoma in female mice. Proc. Soc. exp. Biol. (N.Y.) 40, 421–422 (1939).Google Scholar
  55. Orr, J. W.: Mammary carcinoma in mice following the intranasal administration of methylcholanthrene. J. Path. Bact. 55, 483–488 (1943).CrossRefGoogle Scholar
  56. Prohaska, J.V., Brunschwig, A., Wilson, H.: Oral administration of methylcholanthrene to mice. Arch. Surg. 38, 328–333 (1939).Google Scholar
  57. Rees, E.D., Huggins, W.: Steroid influences on respiration, glycolysis, and levels of pyridine nucleotide-linked dehydrogenases of experimental mammary cancers. Cancer Res. 20, 963–971 (1960).PubMedGoogle Scholar
  58. Rienits, K.G.: The effects of estrone and testosterone on respiration of human mammary cancer in vitro. Cancer 12, 958–961 (1959).CrossRefGoogle Scholar
  59. Riley, P.A., Latter, T., Sutton, P. M.: Hormone assays on breast tumor cultures. Lancet 1973II, 818–821.Google Scholar
  60. Rooks, W.H.: Anti-mammary tumor activities in rats and mice. Methods in Hormone Research, Volume III, Chapter 4, pp. 139–184. New York: Academic Press 1964.Google Scholar
  61. Rooks, W.H., Baba, S., Abe, O., Harada, T., Dorfman, R.I.: Influence of various compounds, particularly steroids, on a transplantable rat mammary fibroadenoma and a transplantable mouse mammary adenocarcinoma. Current Concepts in Breast Cancer, pp. 63–79. Baltimore: Williams and Wilkins Co. 1967.Google Scholar
  62. Segaloff, A.: Hormones and breast cancer. Recent Progr. Hormone Res., 22, 351–379 (1966).PubMedGoogle Scholar
  63. Segaloff, A., Gordon, D., Horwitt, B.N., Schlosser, J.V., Murison, P.J.: Hormonal therapy in cancer of the breast. I. The effect of testosterone propionate therapy on clinical course and hormonal excretion. Cancer 4, 319–323 (1951).PubMedCrossRefGoogle Scholar
  64. Segaloff, A., Horwitt, B.N., Carabasi, R.A., Murison, P.J., Schlosser, J.V.: Hormonal therapy in cancer of the breast. V. The effect of methyltestosterone on clinical course and hormonal excretion. Cancer 6, 483–487 (1953).PubMedCrossRefGoogle Scholar
  65. Shay, H., Aegerter, E.A., Gruenstein, M., Komarov, S.A.: Development of adenocarcinoma of the breast in the Wistar rat following the gastric instillation of methylcholanthrene. J. nat. Cancer Inst. 10, 255–266 (1949).PubMedGoogle Scholar
  66. Shay, H., Gruenstein, M., Kessler, W.B.: Experimental mammary adenocarcinoma of rats: some considerations of methylcholanthrene dosage and hormonal treatment. J. nat. Cancer Inst. 27, 503–513 (1961).Google Scholar
  67. Shay, H., Harris, C., Gruenstein, M.: Influence of sex hormones on the incidence and form of tumors produced in male or female rats by gastric instillation of methylcholanthrene. J. nat. Cancer Inst. 13, 307–331 (1952).PubMedGoogle Scholar
  68. Shay, H., Harris, C., Gruenstein, M.: Studies in prophylaxis of methylcholanthrene induced breast cancer in the rat. Proc. II Internat. Symp. Mammary Cancer, pp.753–764. Univ. Perugia, 1957.Google Scholar
  69. Smith, J.A., King, R.J.B.: Effects of steroids on growth of an androgenindependent mouse mammary carcinoma in cell culture. Exp. Cell. Res. 73, 351–359 (1972).PubMedCrossRefGoogle Scholar
  70. Stock, C.C., Sugiura, K.: Screening steroids against a spectrum of tumors. Ann. N.Y. Acad. Sci. 76, 720–728 (1958).PubMedCrossRefGoogle Scholar
  71. Sutherland, D.J.A., Robins, E.C., Meakin, J.W.: Effects of androgens on Shionogi carcinoma 115 cells in vitro. J. nat. Cancer Inst. 52, 37–48 (1974).PubMedGoogle Scholar
  72. Takatani, O., Kumaoka, S., Abe, O., Sakauchi, N., Sato, R., Mori, H.: The effect of steroidal diosphenol agents on advanced breast cancer. Endocr. Jap. 14, 195–208 (1967).CrossRefGoogle Scholar
  73. Teller, M.N., Stock, C.C., Stohr, G., Merker, P.C., Kaufman, R.J., Escher, G.C., Bowie, M.: Biologic characteristics and chemotherapy of 7, 12-dimethylbenz(a)-anthracene-induced tumors in rats. Cancer Res. 26, 245–252 (1966).PubMedGoogle Scholar
  74. Ulrich, P.: Testosterone (hormone mâle) et son rôle possible dans le traitement de certains cancers du sein. Acta Union Internat. contre Cancer 4, 377 (1939).Google Scholar
  75. Wade, R.: Hormones. Experimental Chemotherapy, Chemotherapy of Neoplastic Diseases, Vol. 5, pp. 133–331. New York: Academic Press 1967.Google Scholar
  76. Yamaguchi, K., Kasai, H., Minesrra, T., Kotch, K., Matsumoto, K.: 5α-Reduction and binding of testosterone in androgen-dependent and -independent mouse mammary tumors. Endocrinology 95, 1424–1430 (1974).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin · Heidelberg 1976

Authors and Affiliations

  • R. Hilf

There are no affiliations available

Personalised recommendations