Effects of Estrogens and Antiestrogens on Cell Proliferation

Implications for the Treatment of Breast Cancer
  • C. Kent Osborne
Part of the Cancer Treatment and Research book series (CTAR, volume 39)

Abstract

It has been recognized for many years that breast cancer in some women is regulated in part by the female sex steroid hormone estrogen. About one-third of human breast carcinomas are ‘hormone-dependent’ and respond to various endocrine manipulations, which are usually designed to block the stimulatory effects of estrogen on tumor growth. Although the mechanisms by which additive hormone therapies, such as pharmacologic estrogens or progestins, inhibit tumor growth have not been defined, treatment by oophorectomy, adrenalectomy, hypophysectomy, luteinizing hormone-releasing hormone (LHRH) super agonists, and aromatase inhibitors such as amino-glutethimide presumably inhibit growth by reducing the concentration of estrogen available to the cancer cell. The nonsteroidal antiestrogens block the effects of endogenous estrogen at the cancer cell itself by competing with estrogen for its receptor.

Keywords

Osteoporosis Flare Doxorubicin Methotrexate Melphalan 

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References

  1. 1.
    Horwitz KB, McGuire WL (1978): Nuclear mechanisms of estrogen action. J Biol Chem 253:8185–8191.PubMedGoogle Scholar
  2. 2.
    Horwitz KB, McGuire WL (1978): Actinomycin D prevents nuclear processing of estrogen receptor. J Biol Chem 253:6319–6322.PubMedGoogle Scholar
  3. 3.
    Eckert RL, Katzenellenbogen BS (1982): Effects of estrogens and antiestrogens on estrogen receptor dynamics and the induction of progesterone receptor receptor in MCF-7 human breast cancer cells. Cancer Res 42:139–144.PubMedGoogle Scholar
  4. 4.
    Eckert RL, Mullick A, Rorke EA, Katzenellenbogen BS (1984): Estrogen receptor synthesis and turnover in MCF-7 breast cancer cells measured by a density shift technique. Endocrinology 114:629–637.PubMedCrossRefGoogle Scholar
  5. 5.
    Lippman M, Bolan G, Huff K (1976): The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. Cancer Res 36:4595–4601.PubMedGoogle Scholar
  6. 6.
    Osborne CK, Lippman ME (1978): Human breast cancer in tissue culture: The effects of hormones. In McGuire WL (ed): Breast Cancer — Advances in Research and Treatment, Vol 2. New York, Plenum, pp 103–154.Google Scholar
  7. 7.
    Aitken SC, Lippman ME (1983): Hormonal regulation of de novo pyrimidine synthesis and utilization in human breast cancer cells in tissue culture. Cancer Res 43:4681–4690.PubMedGoogle Scholar
  8. 8.
    Edwards DP, Murthy SR, McGuire WL (1980): Effects of estrogen and antiestrogen on DNA polymerase in human breast cancer. Cancer Res 40:1722–1726.PubMedGoogle Scholar
  9. 9.
    Rozengurt E, Sinnett-Smith J, Taylor-Papadimitriou J (1985): Production of PDGF-like growth factor by breast cancer cell lines. Int J Cancer 36:247–252.PubMedCrossRefGoogle Scholar
  10. 10.
    Huff KK, Kaufman D, Gabbay KH, et al (1986): Secretion of an insulin-like growth factor-I-related protein by human breast cancer cells. Cancer Res 46:4613–4619.PubMedGoogle Scholar
  11. 11.
    Salomon DS, Zwiebel JA, Bano M, et al (1984): Presence of transforming growth factors in human breast cancer cells. Cancer Res 44:4067–4077.Google Scholar
  12. 12.
    Dickson RB, Bates SE, McManaway ME, Lippman ME (1986): Characterization of estrogen responsive transforming activity in human breast cancer cell lines. Cancer Res 46:1707–1713.PubMedGoogle Scholar
  13. 13.
    Lippman M, Bolan G, Huff K (1976): Interactions of antiestrogens with human breast cancer in long-term tissue culture. Cancer Treat Rep 60:1421–1429.PubMedGoogle Scholar
  14. 14.
    Osborne CK, Boldt DH, Clark GM, Trent JM (1983): Effects of tamoxifen on human breast cancer cell cycle kinetics: accumulation of cells in early G1 phase. Cancer Res 43:3583–3585.PubMedGoogle Scholar
  15. 15.
    Osborne CK, Von Hoff DD, Mullins K (1985): Endocrine therapy testing of human breast cancers in the soft agar clonogenic assay. Breast Cancer Res Treat 6:229–235.PubMedCrossRefGoogle Scholar
  16. 16.
    Briand P, Lykkesfeldt AE (1984): Effect of estrogen and antiestrogen on the human breast cancer cell line MCF-7 adapted to growth at low serum concentration. Cancer Res 44: 1114–1119.PubMedGoogle Scholar
  17. 17.
    Shafie SM (1980): Estrogen and the growth of breast cancer: new evidence suggests indirect action. Science 209:701–702.PubMedCrossRefGoogle Scholar
  18. 18.
    Barnes D, Sato G (1979): Growth of a human mammary tumour cell line in a serum-free medium. Nature 281:388–389.PubMedCrossRefGoogle Scholar
  19. 19.
    Berthois Y, Katzenellenbogen JA, Katzenellenbogen BS (1986): Phenol red in tissue culture media is a weak estrogen: implications concerning the study of estrogen-responsive cells in culture. Proc Natl Acad Sci USA 83:2496–2500.PubMedCrossRefGoogle Scholar
  20. 20.
    Coezy E, Borgna J-L, Rochefort H (1982): Tamoxifen and metabolites in MCF7 cells: correlations between binding to estrogen receptor and inhibition of cell growth. Cancer Res 42: 317–323.PubMedGoogle Scholar
  21. 21.
    Osborne CK, Boldt DH, Estrada P (1984): Human breast cancer cell cycle synchronization by estrogens and antiestrogens in culture. Cancer Res 44:1433–1439.PubMedGoogle Scholar
  22. 22.
    Sutherland RL, Hall RE, Taylor IW (1983): Cell proliferation kinetics of MCF-7 human mammary carcinoma cells in culture and effects of tamoxifen on exponentially growing and plateau-phase cells. Cancer Res 43:3993–4006.Google Scholar
  23. 23.
    Soule HD, McGrath CM (1980): Estrogen responsive proliferation of clonal human breast cancer carcinoma cells in athymic mice. Cancer Lett 10:177–189.PubMedCrossRefGoogle Scholar
  24. 24.
    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.PubMedGoogle Scholar
  25. 25.
    Seibert K, Shafie SM, Triche TJ, et al (1983): Clonal variation of MCF-7 breast cancer cells in vitro and in athymic nude mice. Cancer Res 43:2223–2239.PubMedGoogle Scholar
  26. 26.
    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.PubMedGoogle Scholar
  27. 27.
    Osborne CK, Trent JM, Hobbs K (1987): Biological differences among MCF-7 human breast cancer cell lines from different laboratories. Breast Cancer Res Treat, 9:111–121, 1987.PubMedCrossRefGoogle Scholar
  28. 28.
    Osborne K, Coronado E, Robinson J, Coalson J (1986): Endocrine therapy inhibits proliferation but does not kill human breast cancer cells growing in the nude mouse. Proc AACR 27:219.Google Scholar
  29. 29.
    Fisher B, Redmond C, Brown A, et al (1986): Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the National Surgical Adjuvant Breast and Bowel Project trial. J Clin Oncol 4:459–471.PubMedGoogle Scholar
  30. 30.
    Pearson OH, Hubay CA, Marshall JS, et al (1983): Adjuvant endocrine therapy, cytotoxic chemotherapy, and immunotherapy in stage-II breast cancer: five-year results. Breast Cancer Res Treat 3(suppl 1):61–68.CrossRefGoogle Scholar
  31. 31.
    Benz C, Cadman E, Gwin J et al (1983): Tamoxifen and 5-fluorouracil in breast cancer: cytotoxic synergism in vitro. Cancer Res 43:5298–5303.PubMedGoogle Scholar
  32. 32.
    Hug V, Hortobagyi GN, Drewink B, Finders M (1985): Tamoxifen-citrate counteracts the antitumor effects of cytotoxic drugs in vitro. J Clin Oncol 3:1672–1677.PubMedGoogle Scholar
  33. 33.
    Weichselbaum RR, Hellman S, Piro AJ, et al (1978): Proliferation kinetics of a human breast cancer line in vitro following treatment with 17ß-estradiol and 1-ß-D-arabinofuranosylcy-tosine. Cancer Res 38:2339–2342.PubMedGoogle Scholar
  34. 34.
    Hug V, Johnston D, Finders M, Hortobagyi G (1986): Use of growth-stimulatory hormones to improve the in vitro therapeutic index of doxorubicin for human breast tumors. Cancer Res 46:147–152.PubMedGoogle Scholar
  35. 35.
    Dao TL, Sinha DK, Nemoto T, Patel J (1982): Effect of estrogen and progesterone on cellular replication of human breast tumors. Cancer Res 42:359–362.PubMedGoogle Scholar
  36. 36.
    Conte PF, Fraschini G, Alama A, et al (1985): Chemotherapy following estrogen-induced expansion of the growth fraction of human breast cancer. Cancer Res 45:5926–5930.PubMedGoogle Scholar
  37. 37.
    Allegra JC, Woodcock TM, Richman SP, et al (1982): A phase II trial of tamoxifen, premarin, methotrexate and 5-fluorouracil in metastatic breast cancer. Breast Cancer Res Treat 2:93–99.PubMedCrossRefGoogle Scholar
  38. 38.
    Bowman D (1983): A phase II evaluation of sequential tamoxifen, premarin, methotrexate, and 5-fluorouracil in refractory stage IV breast cancer. Proc ASCO 2:C-413.Google Scholar
  39. 39.
    Lippman ME, Cassidy J, Wesley M, Young RC (1984): A randomized attempt to increase the efficacy of cytotoxic chemotherapy in metastatic breast cancer by hormonal synchronization. J Clin Oncol 2:28–36.PubMedGoogle Scholar
  40. 40.
    Lippman M, Sorace R, Bagley C, et al (1985): Effective systemic management of locally advanced breast cancer. Proc ASCO4:C-249.Google Scholar
  41. 41.
    Conte PF, Pronzato P, Falcone A, et al (1987): Cytokinetic chemotherapy with estrogenic recruitment in locally advanced and metastatic breast cancer. In Iacobelli S (ed): First International Congress on Cancer and Hormones—Rome. Lancashire, England, Parthenon Publishing, in press.Google Scholar
  42. 42.
    Schiffer LM, Braunschweiger PG, Stragand JJ, Poulakos L (1979): The cell kinetics of human mammary cancers. Cancer 43:1707–1719.PubMedCrossRefGoogle Scholar
  43. 43.
    Meyer HS, McDivitt RW, Stone KR, et al (1984): Practical breast carcinoma cell kinetics: review and update. Breast Cancer Res Treat 4:79–88.PubMedCrossRefGoogle Scholar
  44. 44.
    Kodama F, Green GL, Salmon SE (1985): Relation of estrogen receptor expression to clonal growth and antiestrogen effects on human breast cancer cells. Cancer Res 45:2720–2724.PubMedGoogle Scholar
  45. 45.
    Fabian C, Sternson L, El-Serafi M, et al (1981): Clinical pharmacology of tamoxifen in patients with breast cancer. Cancer 48:876–882.PubMedCrossRefGoogle Scholar
  46. 46.
    Whittaker PG, Morgan MRA, Dean PDG, et al (1980): Serum equilin, oestrone, and oestradiol levels in postmenopausal women receiving conjugated equine oestrogens (Premarin). Lancet 1:14–16.PubMedCrossRefGoogle Scholar
  47. 47.
    Suarez AJ, Lamm DL, Radwin HM, et al (1982): Androgen priming and cytotoxic chemotherapy in advanced prostatic cancer. Cancer Chemother Pharmacol 8:261–265.PubMedCrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers, Boston 1988

Authors and Affiliations

  • C. Kent Osborne

There are no affiliations available

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