Summary
Tamoxifen is the endocrine treatment of choice for all women with hormonally responsive breast cancer. 30 years of experience in both the laboratory and clinical setting have shown tamoxifen to be an effective adjuvant treatment with minor short term adverse effects. However, as therapeutic use has extended to 5 years and beyond, and as clinical trials begin which will assess the effectiveness of tamoxifen as a preventive treatment, concern about possible long term adverse effects is justified.
Tamoxifen has an estrogen-like influence on the skeletal and cardiovascular systems, resulting in decreases in both postmenopausal bone loss and low density lipoprotein (LDL) levels. These effects will, it is hoped, result in decreases in the incidences of osteoporosis and coronary heart disease, which are major causes of morbidity and mortality in the postmenopausal age group. Tamoxifen therapy also results in decreased rates of contralateral breast cancer. Long term tamoxifen treatment may result in a small increase in the incidence of endometrial and/or hepatocellular carcinoma, but with millions of women taking tamoxifen for long periods, such small increases in incidence translate to a significant number of women at risk. Tamoxifen is clearly beneficial for short term treatment, but the clinical decision of tamoxifen use in the long term must be made on the individual benefits versus risks of tamoxifen treatment.
Similar content being viewed by others
References
Atlante G, Pozzi M, Vincenzoni C, Vocaturo G. Four case reports presenting new acquisitions on the association between breast and endometrial carcinoma. Gynecologic Oncology 37: 378–380, 1990
Bagdade JD, Wolter J, Subbaiah PV, Ryan W. Effects of tamoxifen treatment on plasma lipids and lipoprotein lipid composition. Journal of Clinical Endocrinology and Metabolism 70: 1132–1135, 1990
Bates EE, Davidson NE, Vilverius EM, Freter CE, Dickson RB, et al. Expression of transforming growth factor alpha and its messenger ribonucleic acid in human breast cancer: its regulation by estrogen and its possible functional significance. Molecular Endocrinology 2: 543–555, 1988
Beatson GT. 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, 162-167, 1896
Beck M, Mills PV. Ocular assessment of patients treated with tamoxifen. Cancer Treatment Reports 63: 1833–1834, 1979
Bertelli G, Pronzato P, Amoroso D, Cusimano MP, Conte PF, et al. Adjuvant tamoxifen in primary breast cancer: Influence on plasma lipids and antithrombin III levels. Breast Cancer Research and Treatment 12: 307–310, 1988
Blackburn AM, Amiel SA, Millis RR, Rubens RD. Tamoxifen and liver damage. British Medical Journal 289: 288–289, 1984
Boccardo F, Rubagotti A, Bruzzi P, Cappellini M, Isola G, et al. Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group. Journal of Clinical Oncology 8: 1310–1320, 1990
Boyd S. On oophorectomy in cancer of the breast. British Medical Journal 2: 1161–1167, 1900
Bruning PF, Bonfrer JM, Hart AA, de Jong-Bakker M, Linders D, et al. Tamoxifen, serum lipoproteins and cardiovascular risk. British Journal of Cancer 58: 497–499, 1988
Bullock JL, Massey FM, Gambrell RD. Use of medroxyprogesterone acetate to prevent menopausal symptoms. Obstetrics and Gynecology 46: 165–168, 1975
Butta A, MacLennan K, Flanders KC, Sacks NP, Smith I, et al. Induction of transforming growth factor β 1 in human breast cancer in vivo following tamoxifen treatment. Cancer Research 52: 4261–4264, 1992
Caleffi M, Fentiman IS, Clark GM, Wang DY, Needham J, et al. Effect of tamoxifen on oestrogen binding, lipid and lipoprotein concentrations and blood clotting parameters in premenopausal women with breast pain. Journal of Endocrinology 119: 335–339, 1988
Cancer facts and figures 1991. American Cancer Society, Inc., Atlanta, 1991
Cancer Research Campaign Adjuvant Breast Trial Working Party. Cyclophosphamide and tamoxifen as adjuvant therapies in the management of breast cancer. British Journal of Cancer 57: 604–607, 1988
Caslelli WP. Cholesterol and lipids in the risk of coronary artery disease — the Framingham Heart Study. Canadian Journal of Cardiology 4(Suppl. A): 5A–10A, 1988
Catherino WH, Jordan VC. Tamoxifen and derivatives. In Droz et al. (Eds) Handbook of chemotherapy in clinical oncology, F.I.I.S., Paris, in press, 1993
Chamness GC, Bannayan GA, Landry LA, et al. Abnormal reproductive devclopmenl in rats after neonatally administered antiestrogen (tamoxifen). Biology of Reproduction 21: 1087–1090, 1979
Chaudary MA, Millis RR, Hoskins EO, Haider M, Bulbrook RD, et al. Bilateral primary breast cancer: a prospective study of disease incidence. British Journal of Surgery 71: 711–714, 1984
Ching CK, Smith PG, Long RG. Tamoxifen-associated hepatocellular damage and agranulocytosis. Lancet 339: 940, 1992
Cole MP, Jones CJA, Todd IDH. A new antioestrogenic agent in late breast cancer. British Journal of Cancer 25: 270–275, 1971
Cole M, Jones C, Todd I. The treatment of advanced carcinoma of the breast with the anti-oestrogenic agent tamoxifen (ICI 46,474) — a series of 96 patients. Advances in Antimicrobial and Antineoplastic Chemotherapy 2: 529–531, 1972
Colletta AA, Wakefield LM, Howell FV, Danielpour D, Baum M, et al. The growth inhibition of human breast cancer cells by a novel synthetic progestin involves the induction of transforming growth factor beta. Journal of Clinical Investigation 87: 277–283, 1991
Colletta AA, Wakefield LM, Howell FV, van Roozendaal KE, Danielpour D, et al. Anti-oestrogens induce the secretion of active transforming growth factor beta from human fetal fibroblasts. British Journal of Cancer 62: 405–409, 1990
Cullen KJ, Smith HS, Hill S, Rosen N, Lippman ME. Growth factor messenger RNA expression by human breast fibroblasts from benign and malignant lesions. Cancer Research 51: 4978–4985, 1991
Cunha GR, Taguchi O, Namikawa R, Nishizuka Y, Robboy SJ. Teratogenic effects of clomiphene, tamoxifen, and diethylstilbestrol on the developing human female genital tract. Human Pathology 8: 1132–1143, 1987
Cuzick J, Baum M. Tamoxifen and contralateral breast cancer. Lancet 2: 282, 1985
Dahan R, Espie M, Mignot L, Houlbert D, Chanu B, et al. Tamoxifen and arterial thrombosis. Lancet 1: 638, 1985
D’Arville CN, Johnson PJ. Growth factors, endocrine aspects and hormonal treatment in hepatocellular carcinoma — an overview. Journal of Steroid Biochemistry and Molecular Biology 37: 1007–1012, 1990
Dodds EC, Goldberg L, Lawson W, Robinson R. Oestrogenic activity of certain synthetic compounds. Nature 141: 246–248, 1938a
Dodds EC, Lawson W, Noble RL. Biological effects of the synthetic oestrogenic substance 4:4-dihydroxy aβ diethylstilbene. Lancet 1: 1389–1391, 1938b
Dotzlaw H, Alkhalaf M, Murphy LC. Characterization of estrogen receptor variant mRNAs from human breast cancers. Molecular Endocrinology 6: 773–785, 1992
Dragan YP, Xu TD, Pitot HC. Tumor promotion as a target for estrogen/antiestrogen effects in rat hepatocarcinogenesis. Preventive Medicine 20: 15–26, 1991
Eagon PK, Porter LE, Fancavilla A, DiLeo A, Van Thiel DH. Estrogen and androgen receptors in liver: their role in liver disease and regeneration. Seminars in Liver Disease 5: 59–69, 1985
Early Breast Cancer Trialists’ Collaborative Group. Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. Lancet 339: 1–15, 71-85, 1992
Enck RE, Rios CN. Tamoxifen treatment of metastatic breast cancer and antithrombin III levels. Cancer 53: 2607–2609, 1984
Engstrom PG, Levin B, Moertel CG, et al. A phase II trial of tamoxifen in hepatocellular carcinoma. Cancer 65: 2641–2643, 1990
Falkson HC, Gray R, Wolberg WH, Gillchrist KW, Harris JE, et al. Adjuvant trial of 12 cycles of CMFPT followed by observation or continuous tamoxifen versus four cycles of CMFPT in postmenopausal women with breast cancer: an Eastern Cooperative Oncology Group phase III study. Journal of Clinical Oncology 8: 599–607, 1990
Farinati F, Fagiuolo S, Rossaro L, Salvagnini M, Chiaramonte M, et al. Prolonged survival in hepatocellular carcinoma patients after anti-oestrogen treatment. Gut 30: A1505, 1989
Farinati F, Salvagnini M, DiMaria F, Fornasiero A, Chiaramonte M, et al. Unresectable hepatocellular carcinoma: a prospective controlled trial with tamoxifen. Journal of Hepatology 11: 297–301, 1990
Fentiman IS, Caleffi M, Rodin A, Murby B, Fogelman I. Bone mineral content of women receiving tamoxifen for mastalgia. British Journal of Cancer 60: 262–264, 1989
Fisher B, Costantino J, Redmond C, Poisson R, Bowman D, et al. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors. New England Journal of Medicine 320: 479–484, 1989
Fisher B, Redmond C, Lagault-Poisson S, Dimitrov NV, Brown AM, et al. Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16. Journal of Clinical Oncology 8: 1005–1018, 1990
Fornander T, Rutqvist LE, Cedarmark B, Gilas U, Mattsson A, et al. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet 2: 117–120, 1989
Fornander T, Rutqvist LE, Sjöberg HE, Blomquist L, Mattsson A, et al. Long-term adjuvant tamoxifen in early breast cancer: effect on bone mineral density in postmenopausal women. Journal of Clinical Oncology 8: 1019–1024, 1990
Francavilla A, Polimeno L, DiLeo A, Barone M, Ove P, et al. The effect of estrogen and tamoxifen on hepatocyte proliferation in vivo and in vitro. Hepatology 9: 614–620, 1989
Friedman MA, Demanes DJ, Hoffman PG. Hepatomas: hormone receptors and therapy. American Journal of Medicine 73: 362–365, 1982
Fritsch M, Wolf DM. Symptomatic side effects of tamoxifen therapy. In Jordan (Ed.) Long term therapy of breast cancer, University of Wisconsin Press, Madison, in press, 1993
Fuqua SAW, Fitzgerald SD, Chamness GC, Tandon AK, McDonnell DP, et al. Variant human breast tumor estrogen receptor with constitutive transcriptional activity. Cancer Research 51: 105–109, 1991
Furr BJA, Jordan VC. Pharmacology and clinical use of tamoxifen. Pharmacology and Therapeutics 25: 127–205, 1984
Gau T. Open letter to all US medical oncologists describing the toxicological findings in rats with high dose tamoxifen treatment, Stuart Pharmaceuticals, Wilmington, 1986
Gerhard I, Runnebaum B. Comparison between tamoxifen and clomiphene therapy in women with anovulation. Archives of Gynecology 227: 279–288, 1989
Gerner EW. Ocular toxicity of tamoxifen. Annals of Ophthalmology 21: 420–423, 1989
Glick JH. Adjuvant chemotherapy trials. In Fowble et al. (Eds) Breast cancer treatment a comprehensive guide to management, pp. 249–254, Mosby-Year Book, Sydney, 1991
Gomm JJ, Smith J, Ryall GK, Baillie R, Turnbull L, et al. Localization of basic fibroblast growth factor and transforming growth factor beta 1 in the human mammary gland. Cancer Research 51: 4685–4692, 1991
Gotfredsen A, Christiansen C, Palshof T. The effect of tamoxifen on bone mineral content in premenopausal women with breast cancer. Cancer 53: 853–857, 1984
Gottardis MM, Jordan VC. The antitumor actions of keoxifene and tamoxifen in the N-nitrosomethylurea-induced rat mammary carcinoma model. Cancer Research 47: 4020–4024, 1987
Gottardis MM, Ricchio ME, Satyaswaroop PG, Jordan VC. Effect of steroidal and nonsteroidal antiestrogens on the growth of a tamoxifen-stimulated human endometrial carcinoma (EnCa101) in athymic mice. Cancer Research 50: 3189–3192, 1990
Gottardis MM, Robinson SP, Jordan VC. Estradiol-stimulated growth of MCF-7 tumors implanted in athymic mice: A model to study the tumoristatic action of tamoxifen. Journal of Steroid Biochemistry 30: 311–314, 1988a
Gottardis MM, Robinson SP, Satyaswaroop PG, Jordan VC. Contrasting actions of tamoxifen on endometrial and breast tumor growth in the athymic mouse. Cancer Research 48: 812–815, 1988b
Graham ML, Krett NL, Miller LA, Leslie KK, Gordon DF, et al. T47Dco cells, genetically unstable and containing estrogen receptor mutations, are a model for the progression of breast cancers to hormone resistance. Cancer Research 50: 6206–6217, 1990
Griffiths F. Tamoxifen retinopathy at low dosage. American Journal of Ophthalmology 15: 185–186, 1987
Gullino PM, Pettigrew HM, Grantham FH. N-Nitrosomethylurea as a mammary carcinogen in rats. Journal of the National Cancer Institute 54: 401–414, 1975
Gusberg SB, Runzwicz CD. Gynecologic Cancer. In Holleb et al. (Eds) American Cancer Society handbook of clinical oncology, pp. 485–487, American Cancer Society, Atlanta, 1991
Han X, Liehr JG. Induction of covalent DNA adducts in rodents by tamoxifen. Cancer Research 52: 1360–1363, 1992
Hardell L. Tamoxifen as a risk factor for carcinoma of corpus uteri. Lancet 2: 563, 1988
Hardell L. Tamoxifen as a risk factor for endometrial cancer. Cancer 66: 1661, 1990
Harper MJK, Walpole AL. A new derivative of triphenylethlene: effect on implantation and mode of action in rats. Journal of Reproduction and Fertility 13: 101–119, 1967
Hendrick A, Subramanian VP. Tamoxifen and thromboembolism. Journal of the American Medical Association 243: 514–515, 1980
Horwitz RI, Feinstein AR. Estrogens and endometrial cancer. Responses to arguments and current status of an epidemiologic controvery. American Journal of Medicine 81: 503–507, 1986
Huggins C, Grand LC, Brillantes P. Mammary cancer induced by a single feeding of polynuclear hydrocarbons and its suppression. Nature 189: 204–207, 1988
ICI Pharmaceuticals Group. Data presented at the Food and Drug Administration Oncology Drugs Advisory Committee Meeting, Bethesda, June 29, 1990
Iino Y, Wolf Dm, Langan-Fahey SM, Johnson DA, Ricchio M, et al. Reversible control of oestradiol-stimulated growth of MCF-7 tumours by tamoxifen in the athymic mouse. British Journal of Cancer 64: 1019–1024, 1991
Iguchi T, Hirokawa M, Takasugi N. Occurrence of genital tract abnormalities and bladder hernia in female mice exposed neonatally to tamoxifen. Toxicology 42: 1–11, 1986
Ingram D. Tamoxifen use, oestrogen binding and serum lipids in postmenopausal women with breast cancer. Australian and New Zealand Journal of Surgery 60: 673–675, 1990
Iqbal MJ, Wilkinson ML, Johnson PJ, Williams R. Sex steroid proteins in foetal, adult and malignant human liver disease. British Journal of Cancer 48: 791–796, 1983
Isles CG, Hole DJ, Hawthorne VM, Lever AF. Relation between coronary risk and coronary mortality in women of the Renfrew and Paisley Survey: comparison with men. Lancet 339: 702–706, 1992
Jacquot C, Graterol R, Bariety J, Capron L, Fiessinger JN, et al. DES versus tamoxifen in advanced breast cancer. New England Journal of Medicine 304: 1041–1043, 1981
Jensen EV, De Sombre ER. Oestrogen-receptor interaction in target tissues. Biochemical Journal 115: 28P–29P, 1969
Jensen EV, Jacobson HI. Basic guides to the mechanism of estrogen action. Recent Progress in Hormone Research 18: 387–414, 1962
Jensen EV, Jacobson HI, Flesher JW, Saha NN, Gupta GN, et al. Estrogen receptors in target tissues. In Nakao et al. (Eds) Steroid dynamics, pp. 133–157, Academic Press, New York, 1967
Johnson PJ. The clinical features and natural history of malignant liver tumours. Clinical Gastroenterology 1: 17–34, 1987
Jordan VC. Laboratory studies to develop general principles for the adjuvant treatemnt of breast cancer with antiestrogens: problems and potential for future clinical applications. Breast Cancer Research and Treatment 3(Suppl. 1): 73–86, 1983
Jordan VC. Biochemical pharmacology of antiestrogen action. Pharmacological Reviews 36: 245–276, 1984
Jordan VC. Long-term adjuvant tamoxifen therapy for breast cancer. Breast Cancer Research and Treatment 15: 125–136, 1990
Jordan VC, Bain RR, Brown RR, Gosden B, Santos MA. Determination and pharmacology of a new hydroxylated metabolite of tamoxifen observed in patient sera during therapy for advanced breast cancer. Cancer Research 43: 1446–1450, 1983
Jordan VC, Collins MM, Rowsby L, Prestwick G. A monohydroxylated metabolite of tamoxifen with potent antioestrogenic activity. Journal of Endocrinology 75: 305–316, 1977
Jordan VC, Gottardis MM, Robinson SP, Friedl A. Immune-deficient animals to study ‘hormone-dependent’ breast and endometrial cancer. Journal of Steroid Biochemistry 31: 169–176, 1989
Jordan VC, Koerner S. Tamoxifen (ICI 46, 474) and the human carcinoma 8S estrogen receptor. European Journal of Cancer 11: 205–206, 1975
Jordan VC, Murphy CS. Endocrine pharmacology of antiestrogens as antitumor agents. Endocrine Reviews 11: 578–610, 1990
Jordan VC, Phelps E, Lindgren JU. Effects of anti-estrogens on bone in castrated and intact female rats. Breast Cancer Research and Treatment 10: 31–35, 1987
Jordan VC, Wolf MF, Mirecki DM, Whitford D, Welshons WV, et al. Hormone receptor assays: clinical usefulness in the management of carcinoma of the breast. Critical Reviews in Clinical and Laboratory Science 26: 97–152, 1988
Kaiser-Kupfer MI, Lippman ME. Tamoxifen retinopathy. Cancer Treatment Reports 62: 315–320, 1978
Kaiser-Kupfer MI, Kupfer C, Rodrigues MM. Tamoxifen retinopathy: a clinicopathologic report. Ophthalmology 88: 89–93, 1981
Kiang DT, Kennedy BJ. Tamoxifen (antiestrogen) therapy in advanced breast cancer. Annals of Internal Medicine 87: 687–690, 1977
Killackey MA, Hakes TB, Pierce VK. Endometrial adenocarcinoma in breast cancer patients receiving antiestrogens. Cancer Treatment Reports 69: 237–238, 1985
Knabbe C, Lippman ME, Wakefield LM, Flanders KC, Kasid A, et al. Evidence that transforming growth factor-β is a hormonally regulated negative growth factor in human cancer cells. Cell 48: 417–428, 1987
Kori SH, Marshall J. Tamoxifen-induced encephalopathy. Neurology 32: A72–A73, 1982
Leaf DA. A woman’s heart: an update of CAD in women. Western Journal of Medicine 149: 751–757, 1988
Lederberg MS, Holland JC. Psycho-oncology. In Kaplan HI & Sadock BJ (Eds) Comprehensive Textbook of Psychiatry, 5th ed., pp. 1251–1253, Williams & Wilkins, Baltimore, 1988
Lerner LJ, Holthaus FJ, Thompson CR. A non-steroidal estrogen antagonist 1-(p-2-diethylaminoethoxyphenyl)-1 -phenyl-2-p-methoxyphenyl ethanol. Endocrinology 63: 295–318, 1958
Lerner LJ, Jordan VC. Development of antiestrogens and their use in breast cancer: Eighth Cain memorial award lecture. Cancer Research 50: 4177–4189, 1990
Lieberman J, Borrero J, Urdaneta E, Wright IS. Thrombophlebitis and cancer. Journal of the American Medical Association 177: 542–545, 1961
Lippman ME, Bolan G. Oestrogen-responsive human breast cancer in long-term tissue culture. Nature 256: 592–595, 1975
Lipton A, Harvey HA, Hamilton RW. Venous thrombosis as a side effect of tamoxifen treatment. Cancer Treatment Reports 68: 887–889, 1984
Longstaff S, Sigurdsson H, O’Keeffe M, Ogston S, Preece P. A controlled study of the ocular effects of tamoxifen in conventional dosage in the treatment of breast carcinoma. European Journal of Cancer and Clinical Oncology 25: 1805–1808, 1989
Loomus GN, Aneja P, Bota RA. A case of peliosis hepatitis in association with tamoxifen therapy. American Journal of Clinical Pathology 80: 881–883, 1983
Love RR. Tamoxifen therapy in primary breast cancer: biology, efficacy, and side effects. Journal of Clinical Oncology 7: 803–815, 1989
Love RR, Mazess RB, Barden HS, Epstein S, Newcomb PA, et al. Effects of tamoxifen on bone mineral density in postmenopausal women with breast cancer. New England Journal of Medicine 326: 852–856, 1992a
Love RR, Mazess RB, Tormey DC, Barden HS, Newcomb PA, et al. Bone mineral density in women with breast cancer treated with adjuvant tamoxifen for at least two years. Breast Cancer Research and Treatment 12: 279–302, 1988
Love RR, Newcomb PA, Weibe DA, Surawicz TS, Jordan VC, et al. Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node-negative breast cancer. Journal of the National Cancer Institute 82: 1327–1332, 1990
Love RR, Surawicz TS, Williams EC. Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy. Archives of Internal Medicine 152: 317–320, 1992b
Love RR, Wiebe DA, Newcomb PA, Cameron L, Leventhal H, et al. Effects of tamoxifen on cardiovascular risk factors in postmenopausal women. Annals of Internal Medicine 115: 860–864, 1991
Malfetano JH. Tamoxifen-associated endometrial carcinoma in postmenopausal breast cancer patients. Gynecologic Oncology 39: 82–84, 1990
Mani C, Kupfer D. Cytochrome P-450-mediated activation and irreversible binding of the antiestrogen tamoxifen to proteins in rat and human liver: possible involvement of flavin-containing monooxygenases in tamoxifen activation. Cancer Research 51: 6052–6058, 1991
Mathew A, Chabon AB, Kabakow B, Drucker M, Hirschman RJ. Endometrial carcinoma in five patients with breast cancer on tamoxifen therapy. New York State Journal of Medicine 90: 207–208, 1990
Maunsell E, Brisson J, Deschenes L. Psychological distress after initial treatment of breast cancer. Cancer 70: 120–125, 1992
McClay EE, Mastrangelo MJ, Bellet RE, Berd D. Comnination chemotherapy and hormonal therapy in the treatment of malignant melanoma. Cancer Treatment Reports 71: 465–469, 1987
McDonald CC, Stewart HJ. Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. British Journal of Medicine 303: 435–437, 1991
McKeown CA, Swartz M, Blom J, Maggiano JM. Tamoxifen retinopathy. British Journal of Ophthalmology 65: 177–179, 1981
Melia WM, Johnson PJ, Williams R. Controlled trial of doxorubicin and tamoxifen versus doxorubicin alone in hepatocellular carcinoma. Cancer Treatment Reports 71: 1213–1216, 1987
Mouridsen H, Palshof T, Patterson J, Battersby L. Tamoxifen in advanced breast cancer. Cancer Treatment Reviews 5: 131–141, 1978
Mouridsen H, Palshof T, Rose C. Therapeutic effect of tamoxifen alone versus tamoxifen in combination with gestagen and oestrogen in advanced breast cancer. Recent Results in Cancer Research 71: 169–171, 1980
Murphy CS, Langan-Fahey S, McCague R, Jordan VC. Structure-function relationships of hydroxylated metabolites of tamoxifen that control the proliferation of estrogen-responsive T47D breast cancer cells in vitro. Molecular Pharmacology 38: 737–783, 1990
Murphy LC, Dotzlaw H. Variant estrogen receptor mRNA species detected in human breast cancer biopsy samples. Molecular Endocrinology 3: 687–693, 1989
Nagasue N, Ito A, Yudaya H, Ogawa Y. Estrogen receptors in hepatocellular carcinoma. Cancer 57: 87–91, 1986
Nayfield SG, Karp JE, Ford LG, Dorr FA, Kramer BS. Potential role of tamoxifen in prevention of breast cancer. Journal of the National Cancer Institute 83: 1450–1459, 1991
Nevasaari K, Heikkinen M, Taskinen PJ. Tamoxifen and thrombosis. Lancet 2: 946–947, 1978
Nolvadex Adjuvant Trial Organization. Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer. Analysis at six years by Nolvadex Adjuvant Trial Organization. Lancet 1: 836–840, 1985
Oon C-J, Friedman MA. Primary hepatocellular carcinoma. Present state of the disease and prospects for the future. Cancer Chemotherapy and Pharmacology 8: 206–210, 1982
Osborne CK, Coronado E, Allred DC, Wiebe V, De Gregorio M. Acquired tamoxifen resistance: correlation with reduced breast tumor levels of tamoxifen and isomerization of trans-4-hydroxytamoxifen. Journal of the National Cancer Institute 83: 1477–1482, 1991
Osborne CK, Hobbs K, Clark GM. Effect of estrogens and antiestrogens on growth of human breast cancer cells in athymic mice. Cancer Research 45: 584–590, 1985
Osborne CK, Kitten L, Arteaga CL. Antagonism of chemotherapy induced cytotoxicity for human breast cancer cells by antiestrogens. Journal of Clinical Oncology 7: 710–717, 1989
Osborne CK, Wiebe VJ, McGuire WL, Ciocca DR, De Gregorio MW. Tamoxifen and isomers of 4-hydroxytamoxifen in tamoxifen-resistant tumors from breast cancer patients. Journal of Clinical Oncology 10: 304–310, 1992
Pannuti F, Martoni A, Fruet F, Marraro D, Strocchi E. New regimen of combination hormone therapy (ME-TA-MAP) in the treatment of advamced breast cancer: a pilot study. Panminerva Medica 23: 157–160, 1981
Pasqualini JR, Nguyen BL, Sumida C, Giambiagi N, Mayrand C. Tamoxifen and progesterone effects in target tissues during the perinatatl period. Journal of Steroid Biochemistry 25: 853–857, 1986
Patterson JS, Baum M. Safety of tamoxifen. Lancet 1: 105, 1978
Patterson JS, Battersbey LA. Tamoxifen: an overview of recent studies in the field of oncology. Cancer Treatment Reports 64: 775–778, 1980
Peck WA, Riggs BL, Bell NH, Wallace RB, Jonston CC, et al. Research directions in osteoporosis. American Journal of Medicine 84: 275–280, 1988
Pink JJ, Jordan VC. Diverse mechanisms od antiestrogen resistance in breast cancer. In Dickson & Lippman (Eds) Drug and hormonal resistance in breast cancer: cellular and molecular mechanisms, Ellis Horwood, Chichester, in press, 1993
Pluss JL, DiBella NJ. Reversible central nervous system dysfunction due to tamoxifen in a patient with breast cancer. Annals of Internal Medicine 101: 652, 1984
Powles TJ, Hardy JR, Ashley SE, Cosgrove D, Davey JB, et al. A pilot trial to evaluate the acute toxicity and feasibility of tamoxifen for prevention of breast cancer. British Journal of Cancer 60: 126–131, 1989
Powles TJ, Tillyer CR, Jones AL, Ashley SE, Treleaven J, et al. Prevention of breast cancer with tamoxifen — an update on the Royal Marsden Hospital pilot programme. European Journal of Cancer 26: 680–684, 1990
Pubesgaard T, Von Eyben FE. Bilateral optic neuritis evolved during tamoxifen treatment. Cancer 58: 383–386, 1986
Rasche H, Dietrich M. Hemostatic abnormalities associated with malignant diseases. European Journal of Cancer 13: 1053–1064, 1977
Recchia F, Passalacqua G, Radarigo C. Hepatocellular carcinoma: the long-term response to tamoxifen. A clinical report and review of literature. Minerva Medica 301: 1363–1366, 1989
Robinson SP, Mauel DA, Jordan VC. Antitumor actions of toremifene in the 7, 12-dimethylbenzantracene (DMBA)-induced rat mammary tumor model. European Journal of Cancer and Clinical Oncology 24: 1817–1821, 1988
Roesdahl K. Tamoxifen treatment of advanced breast carcinoma. Acta Radiologica: Oncology, Radiation Therapy, Physics and Biology 18: 203–208, 1979
Ron IG, Inbar MJ, Barak T, Stier S, Chaitchik S. Organic delusional syndrome associated with tamoxifen treatment. Cancer 69: 1415–1417, 1992
Rössner S, Wallgren A. Serum lipoproteins and proteins after breast cancer surgery and effects of tamoxifen. Atherosclerosis 52: 339–346, 1984
Saphner T, Tormey DC, Gray R. Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer. Journal of Clinical Oncology 9: 286–291, 1991
Satyaswaroop PG, Zaino RJ, Mortel R. Estrogen-like effects of tamoxifen on human endometrial carcinoma transplanted into nude mice. Cancer Research 44: 4006–4010, 1984
Sawka CA, Pritchard KI, Paterson AH, Sutherland DJ, Thomson DB, et al. Role and mechanism of action of tamoxifen in premenopausal women with metastatic breast carcinoma. Cancer Research 46: 3152–3156, 1986
Schiff I, Tulchinsky D, Cramer D, Ryan KJ. Oral medroxyprogesterone in the treatment of postmenopausal symptoms. Journal of the American Medical Association 244: 1443–1445, 1980
Shafie SM, Grantham FH. Role of hormones in the growth and regression of human breast cancer cells (MCF-7) transplanted into athymic mice. Journal of the National Cancer Institute 67: 51–56, 1981
Soule HD, McGrath CM. Estrogen proliferation of clonal human breast carcinoma cells in athymic mice. Cancer Letters 10: 51–56, 1980
Stewart PJ, Stern PH. Effects of the antiestrogens tamoxifen and clomiphene on bone resorption in vitro. Endocrinology 118: 125–131, 1986
Sutherland RL, Reddel RR, Murphy LC, Taylor IW. Effects of antiestrogens on cell cycle progression. In Jordan (Ed.) Estrogen/antiestrogen action and breast cancer therapy, pp. 265–281, University of Wisconsin Press, Madison, 1986
Swain SM, Lippman ME. Endocrine therapies of cancer. In Chabner et al. (Eds) Cancer chemotherapy principles and practice, pp. 85–86, JP Lippincott Company, Sydney, 1990
Trodella L, Ausilli-Cefaro GP, Turriziani A, Saccheri S, Venturo I, et al. Combination therapy with progestins and tamoxifen in advanced breast cancer: a preliminary report. American Journal of Clinical Oncology 5: 495–499, 1982
Turner RT, Wakely GK, Hannon KS, Bell NH. Tamoxifen inhibits osteoclast-mediated resorption of trabecular bone in ovarian hormone-deficient rats. Endocrinology 122: 1146–1160, 1988
Veronesi A, Frustaci S, Tirelli U, Galligioni E, Trovo MG, et al. Tamoxifen therapy in postmenopausal advanced breast cancer. Tumori 67: 235–238, 1981
Vinding T, Nielsen NV. Retinopathy caused by treatment with tamoxifen in low dosage. Acta Ophthalmologica 61: 45–50, 1983
Walpole A, Paterson E. Synthetic oestrogens in mammary cancer. Lancet 2: 783–789, 1949
Westerberg H, Nordenskjold B, DeSchryver A, Notter G. Antioestrogen therapy of advanced mammary carcinoma. Acta Radiologica: Oncology, Radiation Therapy, Physics and Biology 15: 513–518, 1976
Wiebe VJ, Osborne CK, McGuire WL, De Gregorio MW. Identification of estrogenic tamoxifen metabolite(s) in tamoxifen-resistant human breast tumors. Journal of Clinical Oncology 10: 990–994, 1992
Williamson JG, Ellis JD. The induction of ovulation by tamoxifen. Journal of Obstetrics and Gynaecology of the British Commonwealth 80: 844–847, 1973
Wolf DM, Parker CP, Langan-Fahey SM, Jordan VC. Investigation of the mechanism of tamoxifen stimulated breast tumor growth using non-isomerizable (fixed-ring) analogs of tamoxifen and its metabolites. Proceedings of the American Association for Cancer Research 33: 463, 1991
Wolter J, Ryan WG, Subbaiah V, Bagdade JD. Apparent beneficial effects of tamoxifen on serum lipoprotein subfractions and bone mineral content in patients with breast cancer. Proceedings of the American Society of Clinical Oncology 7: 10, 1988
Yager JD, Roebuck BD, Paluszcyk TL, Memoli VA. Effects of ethinyl estradiol and tamoxifen on liver DNA turnover and new synthesis and appearance of gamma glutamyl transpeptidase-positive foci in female rats. Carcinogenesis 7: 2007–2014, 1986
Zugmaier G, Ennis BW, Deschauer B, Katz D, Knabbe C, et al. Transforming growth factors type beta 1 and 2 are equipotent growth inhibitors of human breast cancer cell lines. Journal of Cell Physiology 141: 353–356, 1989
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Catherino, W.H., Jordan, V.C. A Risk-Benefit Assessment of Tamoxifen Therapy. Drug-Safety 8, 381–397 (1993). https://doi.org/10.2165/00002018-199308050-00005
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002018-199308050-00005