Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Tamoxifen: a most unlikely pioneering medicine

Abstract

For more than 25 years, tamoxifen has been the gold standard for the endocrine treatment of all stages of oestrogen-receptor-positive breast cancer, and the World Health Organization lists tamoxifen as an essential drug for the treatment of breast cancer. It is estimated that more than 400,000 women are alive today as a result of tamoxifen therapy, and millions more have benefited from palliation and extended disease-free survival. Interestingly, tamoxifen also became the first cancer chemopreventive approved by the Food and Drug Administration (FDA) for the reduction of breast-cancer incidence in both pre- and post-menopausal women at high risk. However, 40 years ago, it was hard to imagine that a non-toxic targeted treatment for breast cancer could be developed at all.

This is a preview of subscription content

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Figure 1: Getting the right formula.
Figure 2: Tamoxifen and beyond.

References

  1. 1

    Baumler, E. Paul Ehrlich: Scientist for Life (Holmes & Meier, New York, 1984).

    Google Scholar 

  2. 2

    Harper, M. J. & Walpole, A. L. Contrasting endocrine activities of cis and trans isomers in a series of substituted triphenylethylenes. Nature 212, 87 (1966).

    CAS  Article  Google Scholar 

  3. 3

    Harper, M. J. & Walpole, A. L. A new derivative of triphenylethylene: effect on implantation and mode of action in rats. J. Reprod. Fertil. 13, 101–119 (1967). First detailed report of the antifertility activity of tamoxifen in rats. The anti-oestrogen lowered circulating cholesterol but did not increase desmosterol.

    CAS  Article  Google Scholar 

  4. 4

    Harper, M. J. & Walpole, A. L. Mode of action of I. C. I. 46,474 in preventing implantation in rats. J. Endocrinol. 37, 83–92 (1967).

    CAS  Article  Google Scholar 

  5. 5

    Cole, M. P., Jones, C. T. & Todd, I. D. A new anti-oestrogenic agent in late breast cancer. An early clinical appraisal of ICI46474. Br. J. Cancer 25, 270–275 (1971). Reports the first clinical study to show tamoxifen had equivalent efficacy to historical results of standard endocrine therapy, but with fewer side effects.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  6. 6

    Ward, H. W. Anti-oestrogen therapy for breast cancer: a trial of tamoxifen at two dose levels. Br. Med. J. 1, 13–14 (1973).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  7. 7

    Ingle, J. N. et al. Randomized clinical trial of diethylstilbestrol versus tamoxifen in postmenopausal women with advanced breast cancer. N. Engl. J. Med. 304, 16–21 (1981).

    CAS  Article  Google Scholar 

  8. 8

    Beatson, G. T. On the treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment with illustrative cases. Lancet 2, 104–107 (1896).

    Article  Google Scholar 

  9. 9

    Boyd, S. On oophorectomy in cancer of the breast. BMJ 2, 1161–1167 (1900).

    Article  Google Scholar 

  10. 10

    Lathrop, A. E. & Loeb, L. Further investigations on the origins of tumors in mice III on the part played by internal secretions in the spontaneous development of tumors. J. Cancer Res. 1, 1–19 (1916).

    CAS  Google Scholar 

  11. 11

    Lacassagne, A. Hormonal pathogenesis of adenocarcinoma of the breast. Am. J. Cancer 27, 217–225 (1936).

    Article  Google Scholar 

  12. 12

    Lerner, L. J. in Nonsteroidal Antioestrogens: Molecular Pharmacology and Antitumour Activity (eds. Sutherland, R. L. & Jordan, V. C.) 1–6 (Sydney Academic Press, Sydney, Australia, 1981).

    Google Scholar 

  13. 13

    Lerner, L. J., Holthaus, J. F. & Thompson, C. R. A non-steroidal estrogen antagonist 1-(p-2-diethylaminoethoxyphenyl)-1-phenyl-2-p-methoxyphenylethanol. Endocrinology 63, 295–318 (1958). The initial report of the anti-oestrogen actions of a nonsteroidal compound. The compound was, unlike tamoxifen, anti-oestrogenic in all species tested.

    CAS  Article  Google Scholar 

  14. 14

    Duncan, G. W., Lyster, S. C., Clark, J. J. & Lednicer, D. Antifertility activities of two diphenyl-dihydroaphthalene derivatives. Proc. Soc. Exp. Biol. Med. 112, 439–442 (1963).

    CAS  Article  Google Scholar 

  15. 15

    Legha, S. S., Slavik, M. & Carter, S. K. Nafoxidine — an antiestrogen for the treatment of breast cancer. Cancer 38, 1535–1541 (1976).

    CAS  Article  Google Scholar 

  16. 16

    Holtkamp, D. E., Greslin, S. C., Root, C. A. & Lerner, L. J. Gonadotropin inhibiting and antifecundity effects of chloramiphene. Proc. Soc. Exp. Biol. Med. 105, 197–201 (1960).

    CAS  Article  Google Scholar 

  17. 17

    Greenblatt, R. B., Barfield, W. E., Jungck, E. C. & Ray, A. W. Induction of ovulation with MRL-41 — Preliminary Report. JAMA 178, 101–104 (1961).

    CAS  Article  Google Scholar 

  18. 18

    Greenblatt, R., Roy, S. & Mahesh, V. The induction of ovulation. Am. J. Obstet. Gynecol. 84, 900–912 (1962).

    Article  Google Scholar 

  19. 19

    Whitelaw, M. J. Clomiphene citrate experience with 217 patients. Fertil. Steril. 17, 584–604 (1966).

    CAS  Article  Google Scholar 

  20. 20

    Herbst, A. L., Griffiths, C. T. & Kistner, R. W. Clomiphene citrate (NSC-35770) in disseminated mammary carcinoma. Cancer Chemother. Rep. 43, 39–41 (1964).

    CAS  Google Scholar 

  21. 21

    Bloom, H. J. G. & Boesen, E. Antioestrogens in treatment of breast cancer: value of nafoxidine in 52 advanced cases. Br. Med. J. 2, 7–12 (1974).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  22. 22

    William S. Merrel Company. Official Literature on New Drugs: Clomiphene citrate (Clomid). Clin. Pharmacol. Ther. 8, 891–897 (1967).

    Article  Google Scholar 

  23. 23

    Hollander, W., Chobanian, A. V. & Wilkins, R. W. The effects of triparanol (MER-29) in subjects with and without coronary artery disease. JAMA 174, 87–94 (1960).

    Article  Google Scholar 

  24. 24

    Laughlin, R. C. & Carey, T. F. Cataracts in patients treated with triparanol. JAMA 181, 369–370 (1962).

    Article  Google Scholar 

  25. 25

    Avigan, J., Steinberg, D., Vroman, H. E., Thompson, M. J. & Mosettig, E. Studies of cholesterol biosynthesis. The identification of desmosterol in serum and tissues of animals and man treated with MER29. J. Biol. Chem. 235, 3123–3126 (1960).

    CAS  Google Scholar 

  26. 26

    Kraft, R. O. Triparanol in the treatment of disseminated mammary carcinoma. Cancer Chemother. Rep. 25, 113–115 (1962).

    CAS  Google Scholar 

  27. 27

    Haddow, A., Watkinson, J. M. & Paterson, E. Influence of synthetic oestrogens upon advanced malignant disease. BMJ 2, 393–398 (1944).

    CAS  Article  Google Scholar 

  28. 28

    Walpole, A. L. & Paterson, E. Synthetic oestrogens in mammary cancer. Lancet 2, 783–789 (1949).

    CAS  Article  Google Scholar 

  29. 29

    Bedford, G. & Richardson, D. N. Preparation and identification of cis and trans isomers of a substituted triphenylethylene. Nature 212, 733–734 (1966).

    CAS  Article  Google Scholar 

  30. 30

    Kilbourn, B., Mais, R. H. B. & Owston, P. G. Identification of isomers of a substituted triphenylethylene: the crystal structure of 1-p-(2-dimethylaminoethoxyphenyl)1,2 cis diphenyl but1–ene hydrobromide. Chem. Commun. 1, 291 (1968).

    Google Scholar 

  31. 31

    Labhsetwar, A. P. Role of oestrogen in spontaneous ovulation demonstrated by use of an antagonist of oestrogen ICI46,474. Nature 225, 80–81 (1970).

    CAS  Article  Google Scholar 

  32. 32

    Labhsetwar, A. P. Role of estrogen in ovulation a study using estrogen antagonist ICI46,474. Endocrinology 87, 542–551 (1970).

    CAS  Article  Google Scholar 

  33. 33

    Labhsetwar, A. P. Effects of antioestrogen on the corpus luteum of rabbits and rats. J. Reprod. Fertil. 25, 295–297 (1971).

    CAS  Article  Google Scholar 

  34. 34

    Labhsetwar, A. P. Role of estrogen in spontaneous ovulation: evidence for positive feedback in hamsters. Endocrinology 90, 941–946 (1972).

    CAS  Article  Google Scholar 

  35. 35

    Jordan, V. C. The development of tamoxifen for breast cancer therapy: a tribute to the late Arthur L. Walpole. Breast Cancer Res. Treat. 11, 197–209 (1988).

    CAS  Article  Google Scholar 

  36. 36

    Klopper, A. & Hall, M. New synthetic agent for the induction of ovulation. Preliminary trial in women. Br. Med. J. 1, 152–154 (1971).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  37. 37

    Williamson, J. G. & Ellis, J. D. The induction of ovulation by tamoxifen. J. Obstet. Gynaecol. Br Commonwealth 80, 844–847 (1973).

    CAS  Article  Google Scholar 

  38. 38

    El-Sheikha, Z., Klopper, A. & Beck, J. S. Treatment of menometrorrhagia with an anti-oestrogen. Clin. Endocrinology 1, 275–282 (1972).

    CAS  Article  Google Scholar 

  39. 39

    Palopoli, F. P., Feil, V. J., Allen, R. F., Holtkamp, D. E., and Richardson Jr., A. Substituted aminoalkoxyl-triarylhaloethylenes. J. Med. Chem. 10, 84–86 (1967).

    CAS  Article  Google Scholar 

  40. 40

    Ernst, S., Hite, G., Cantrell, J. S., Richardson Jr., A. & Benson, H. D. Stereochemistry of geometric isomers of clomiphene: a correction of structure–activity relationships. J. Pharm. Sci. 65, 148–150 (1976).

    CAS  Article  Google Scholar 

  41. 41

    Emmens, C. W. Postcoital contraception. Br. Med. Bull. 26, 45–51 (1970).

    CAS  Article  Google Scholar 

  42. 42

    Lunan, C. B. & Klopper, A. Antioestrogens: a review. Clin. Endocrinology 4, 551–572 (1975).

    CAS  Article  Google Scholar 

  43. 43

    Huggins, C., Grand, L. C. & Brillantes, F. P. Mammary cancer induced by a single feeding of polynuclear hydrocarbons and their suppression. Nature 189, 204 (1961).

    CAS  Article  Google Scholar 

  44. 44

    Jensen, E. V. & Jacobson, H. I. Basic guides to the mechanism of estrogen action. Recent Prog. Horm. Res. 18, 387–414 (1962). The pioneering studies to show the target site-specific action of radiolabelled oestradiol injected into immature rats.

    CAS  Google Scholar 

  45. 45

    Jensen, E. V., Block, G. E., Smith, S., Kyser, K. & DeSombre, E. R. Estrogen receptors and breast cancer response to adrenalectomy. Natl Cancer Inst. Monogr. 34, 55–70 (1971).

    CAS  Google Scholar 

  46. 46

    Skidmore, J. R., Walpole, A. L. & Woodburn, J. Effect of some triphenylethylenes on oestradiol binding in vitro to macromolecules from uterus and anterior pituitary. J. Endocrinol. 52, 289–298 (1972).

    CAS  Article  Google Scholar 

  47. 47

    Jordan, V. C., Collins, M. M., Rowsby, L. & Prestwich, G. A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. J. Endocrinol. 75, 305–316 (1977). The first study to show that tamoxifen, with a low affinity for the oestrogen receptor, was converted to anti-oestrogenic metabolites with high affinity. The publication of these data was delayed for more than a year to secure patent protection for the metabolites (note that tamoxifen did not have patent protection in the United States at the time.)

    CAS  Article  Google Scholar 

  48. 48

    Allen, K. E., Clark, E. R. & Jordan, V. C. Evidence for the metabolic activation of non-steroidal antioestrogens: a study of structure-activity relationships. Br. J. Pharmacol. 71, 83–91 (1980).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49

    Jordan, V. C. & Koerner, S. Tamoxifen (ICI 46,474) and the human carcinoma 8S oestrogen receptor. Eur. J. Cancer. 11, 205–206 (1975).

    CAS  Article  Google Scholar 

  50. 50

    Nicholson, R. I. & Golder, M. P. The effect of synthetic anti-oestrogens on the growth and biochemistry of rat mammary tumours. Eur. J. Cancer 11, 571–579 (1975).

    CAS  Article  Google Scholar 

  51. 51

    Jordan, V. C. & Dowse, L. J. Tamoxifen as an antitumour agent: effect on oestrogen binding. J. Endocrinol. 68, 297–303 (1976).

    CAS  Article  Google Scholar 

  52. 52

    Jordan, V. C. Effect of tamoxifen (ICI 46,474) on initiation and growth of DMBA-induced rat mammary carcinomata. Eur. J. Cancer 12, 419–424 (1976). Demonstrated that tamoxifen could not only be used to treat mammary cancer, but would also act as a preventative.

    CAS  Article  Google Scholar 

  53. 53

    Jordan, V. C. & Jaspan, T. Tamoxifen as an antitumour agent: oestrogen binding as a predictive test for tumour response. J. Endocrinol. 68, 453–460 (1976).

    CAS  Article  Google Scholar 

  54. 54

    Kiang, D. T. & Kennedy, B. J. Tamoxifen (antiestrogen) therapy in advanced breast cancer. Ann. Intern. Med. 87, 687–690 (1977).

    CAS  Article  Google Scholar 

  55. 55

    NATO. Controlled trial of tamoxifen as adjuvant agent in management of early breast cancer. Interim analysis at four years by Nolvadex Adjuvant Trial Organisation. Lancet 1, 257–261 (1983).

  56. 56

    NATO. Controlled trial of tamoxifen as a single adjuvant agent in the management of early breast cancer. 'Nolvadex' Adjuvant Trial Organisation. Br. J. Cancer 57, 608–611 (1988).

  57. 57

    EBCTCG. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351, 1451–1467 (1998).

  58. 58

    Colletta, A. A., Benson, J. R. & Baum, M. Alternative mechanisms of action of antioestrogens. Breast Cancer Res. Treat. 31, 5–9 (1994).

    CAS  Article  Google Scholar 

  59. 59

    Lippman, M. E. & Bolan, G. Oestrogen-responsive human breast cancer in long term tissue culture. Nature 256, 592–593 (1975).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  60. 60

    Jordan, V. C. & Allen, K. E. Evaluation of the antitumour activity of the non-steroidal antioestrogen monohydroxytamoxifen in the DMBA-induced rat mammary carcinoma model. Eur. J. Cancer 16, 239–251 (1980). The first study to demonstrate, in the laboratory, that long-term anti-oestrogen therapy and a strategy of complete oestrogen blockade was going to be the best way to treat patient with receptor-positive disease.

    CAS  Article  Google Scholar 

  61. 61

    Jordan, V. C., Dix, C. J. & Allen, K. E. in Adjuvant Therapy of Cancer (eds Salmon, S. E. & Jones, S. E.) 19–26 (Grune & Stratton, Inc., New York, 1979).

    Google Scholar 

  62. 62

    Jordan, V. C. in Reviews on Endocrine-related Cancer 49–55 (October Supplement) (1978).

    Google Scholar 

  63. 63

    Jordan, V. C., Allen, K. E. & Dix, C. J. Pharmacology of tamoxifen in laboratory animals. Cancer Treat. Rep. 64, 745–759 (1980).

    CAS  Google Scholar 

  64. 64

    Baum, M. et al. Improved survival among patients treated with adjuvant tamoxifen after mastectomy for early breast cancer. Lancet 2, 450 (1983). Clinical report demonstrating that extended adjuvant tamoxifen therapy saved lives.

    CAS  Article  Google Scholar 

  65. 65

    Fisher, B., Dignam, J., Bryant, J. & Wolmark, N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J. Natl Cancer Inst. 93, 684–690 (2001).

    CAS  Article  Google Scholar 

  66. 66

    Osborne, C. K., Coronado, E. B. & Robinson, J. P. Human breast cancer in the athymic nude mouse: cytostatic effects of long-term antiestrogen therapy. Eur. J. Cancer Clin. Oncol. 23, 1189–1196 (1987).

    CAS  Article  Google Scholar 

  67. 67

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

    CAS  Google Scholar 

  68. 68

    Jordan, V. C., Phelps, E. & Lindgren, J. U. Effects of anti-estrogens on bone in castrated and intact female rats. Breast Cancer Res. Treat. 10, 31–35 (1987). The first report that both tamoxifen and raloxifene would maintain bone density selectively, despite the fact that both prevented mammary cancer in rats.

    CAS  Article  Google Scholar 

  69. 69

    Jordan, V. C. & Robinson, S. P. Species-specific pharmacology of antiestrogens: role of metabolism. Fed. Proc. 46, 1870–1874 (1987). Initial report that the tamoxifen–oestrogen-receptor complex would switch on or switch off oestrogen action selectively in different target tissues.

    CAS  Google Scholar 

  70. 70

    Jordan, V. C. Selective estrogen receptor modulation: a personal perspective. Cancer Res. 61, 5683–5687 (2001).

    CAS  Google Scholar 

  71. 71

    Love, R. R. et al. Effects of tamoxifen on cardiovascular risk factors in postmenopausal women. Ann. Intern. Med. 115, 860–864 (1991).

    CAS  Article  Google Scholar 

  72. 72

    Love, R. R. et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. N. Engl J. Med. 326, 852–856 (1992). The first prospective randomized study to demonstrate that tamoxifen had the potential to increase bone density in postmenopausal patients. This study built on previous laboratory work.

    CAS  Article  Google Scholar 

  73. 73

    Gottardis, M. M. & Jordan, V. C. Antitumor actions of keoxifene and tamoxifen in the N-nitrosomethylurea-induced rat mammary carcinoma model. Cancer Res. 47, 4020–4024 (1987).

    CAS  Google Scholar 

  74. 74

    Jordan, V. C., Lababidi, M. K. & Langan-Fahey, S. Suppression of mouse mammary tumorigenesis by long-term tamoxifen therapy. J. Natl Cancer Inst. 83, 492–496 (1991).

    CAS  Article  Google Scholar 

  75. 75

    Cuzick, J. & Baum, M. Tamoxifen and contralateral breast cancer. Lancet 2, 282 (1985).

    CAS  Article  Google Scholar 

  76. 76

    Fisher, B. et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J. Natl Cancer Inst. 90, 1371–1388 (1998). First prospective randomized trial of high-risk pre- and postmenopausal women to demonstrate that tamoxifen reduces the risk of breast cancer. The paper confirmed all prior predictions about selective oestrogen-receptor modulation.

    CAS  Article  Google Scholar 

  77. 77

    IBIS Investigators. First results from the International Breast Study: a randomized prevention trial. Lancet 360, 817–824 (2002).

  78. 78

    Powles, T. J. et al. A pilot trial to evaluate the acute toxicity and feasibility of tamoxifen for prevention of breast cancer. Br. J. Cancer 60, 126–131 (1989).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  79. 79

    Powles, T. et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet 352, 98–101 (1998).

    CAS  Article  Google Scholar 

  80. 80

    Gail, M. H. et al. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J. Natl Cancer Inst. 81, 1879–1886 (1989).

    CAS  Article  Google Scholar 

  81. 81

    Satyaswaroop, P. G., Zaino, R. J. & Mortel, R. Estrogen-like effects of tamoxifen on human endometrial carcinoma transplanted into nude mice. Cancer Res. 44, 4006–4010 (1984).

    CAS  Google Scholar 

  82. 82

    Gottardis, M. M., Robinson, S. P., Satyaswaroop, P. G. & Jordan, V. C. Contrasting actions of tamoxifen on endometrial and breast tumor growth in the athymic mouse. Cancer Res. 48, 812–815 (1988). The first study to illustrate the target site-specificity of tamoxifen in endometrial and breast cancer. The authors suggested screening of women who were taking adjuvant tamoxifen.

    CAS  Google Scholar 

  83. 83

    Fornander, T. et al. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet 1, 117–120 (1989).

    CAS  Article  Google Scholar 

  84. 84

    Fisher, B. et al. Endometrial cancer in tamoxifen-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. J. Natl Cancer Inst. 86, 527–537 (1994).

    CAS  Article  Google Scholar 

  85. 85

    Greaves, P., Goonetilleke, R., Nunn, G., Topham, J. & Orton, T. Two-year carcinogenicity study of tamoxifen in Alderley Park Wistar-derived rats. Cancer Res. 53, 3919–3924 (1993).

    CAS  Google Scholar 

  86. 86

    Jordan, V. C. What if tamoxifen (ICI 46,474) had been found to produce rat liver tumors in 1973? A personal perspective. Ann. Oncol. 6, 29–34 (1995).

    CAS  Article  Google Scholar 

  87. 87

    Ettinger, B. et al. Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282, 637–645 (1999).

    CAS  Article  Google Scholar 

  88. 88

    Cummings, S. R. et al. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA 281, 2189–2197 (1999). Clinical proof of the concept proposed in 1990 ( Cancer Res 50, 477–489) that women taking a selective oestrogen-receptor modulator to prevent or treat osteoporosis would have a reduced incidence of breast cancer.

    CAS  Article  Google Scholar 

  89. 89

    Buzdar, A. U., Marcus, C., Holmes, F., Hug, V. & Hortobagyi, G. Phase II evaluation of Ly156758 in metastatic breast cancer. Oncology 45, 344–345 (1988).

    CAS  Article  Google Scholar 

  90. 90

    Jordan, V. C. Designer estrogens. Sci. Am. 279, 60–67 (1998).

    CAS  Article  Google Scholar 

  91. 91

    Writing Group for the Women's Health Initiative Investigators. Risks and benefits of estrogen plus progestin in healthy postmenopausal women principal results from the women's health initiative randomized controlled trial. JAMA 288, 321–333 (2002).

  92. 92

    Wakeling, A. E., Dukes, M. & Bowler, J. A potent specific pure antiestrogen with clinical potential. Cancer Res. 51, 3867–3873 (1991).

    CAS  Google Scholar 

  93. 93

    The ATAC Trialist Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomized trial. Lancet 359, 2131–2139 (2002).

  94. 94

    Osborne, C. K. et al. Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J. Clin. Oncol. 20, 3386–3395 (2002).

    CAS  Article  Google Scholar 

  95. 95

    Howell, A. et al. Fulvestrant, formerly ICI 182,780, is as effective as anastrozole in postmenopausal women with advanced breast cancer progressing after prior endocrine treatment. J. Clin. Oncol. 20, 3396–3403 (2002).

    CAS  Article  Google Scholar 

  96. 96

    McGuire, W. L., Carbone, P. R., Sears M. F. & Escher, G. C. in Oestrogen Receptors in Human Breast Cancer (eds McGuire, W. L., Carbone, P. R. & Volmer, E. P.) 6 (Raven, New York, 1975).

    Google Scholar 

Download references

Acknowledgements

I would like to thank Alexandra Jordan for assistance with the patenting history of tamoxifen. Most importantly, I want to acknowledge the role of the late Arthur Walpole (who died in 1977), Lois Trench and Roy Cotton for investing in the development of my laboratory ideas at the beginning and Elwood Jensen for his guidance and support throughout my career.

Author information

Affiliations

Authors

Related links

Related links

DATABASES

Cancer.gov

Breast cancer

colon cancer

endometrial cancer

Online Mendelian Inheritance in Man

Coronary heart disease

Osteoporosis

FURTHER INFORMATION

Encyclopedia of Life Sciences

Breast cancer

Oestrogens, mood and cognition

Paul Ehrlich

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Jordan, V. Tamoxifen: a most unlikely pioneering medicine. Nat Rev Drug Discov 2, 205–213 (2003). https://doi.org/10.1038/nrd1031

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing