Skip to main content
Log in

Tamoxifen

A Review of Pharmacoeconomic and Quality-of-Life Considerations for its Use as Adjuvant Therapy in Women with Breast Cancer

  • Pharmacoeconomic Drug Evaluation
  • Published:
PharmacoEconomics Aims and scope Submit manuscript

Summary

Synopsis

Extensive clinical experience, summarised in the recent overview of the Early Breast Cancer Trialists’ Col/aboraliFe Group (EBCTCG). have confirmed that tamoxifen reduces the rate of both disease recurrence and mortality when administered as adjuvant therapy in women with early breast cancer. Tamoxifen is now established as the preferred adjuvant agent in post menopausal women; in particular, patients with node-positive, estrogen receptor-positive breast cancer have the most to gain from tamoxifen therapy. Data from a decision-analysis model indicated that tamoxifen monotherapy had a cost-utility ratio [$US6ooo per additional quality-adjusted life-year (QAL Y), in 1989 dollars] 5 to 6 times lower than that cited as the cost-acceptability cut-off point in the Us.

While tamoxifen monotherapy is effective in postmenopausal women, the EBCTCG overview findings indicate that a combined regimen of tamoxifen and antineoplastic chemotherapy has superior efficacy in the same patient group. An issue of current interest is whether the added benefit offered by such a regimen can by justified in terms of added toxicity and cost. Data from a decision analysis model indicate that combined therapy has a high incremental cost-utility ratio ($US58 000 per additional QALY, in 1989 dollars) compared with no therapy in postmenopausal women. However, the qualily-oflife measures TWiST (Time Without Symptoms and Toxicity) and Q-TWiST (quality-adjusted TWiST) indicate that the early toxicity associated with a combined regimen appears to be justified given the superior long term benefit. Patient preference data from I study further indicate that the degree of benefit offered by a combined regimen would be acceptable to the majority (73%) of patients.

Other areas where pharmacoeconomic analyses may help define more closely the optimal use of adjuvant tamoxifen is in patients at low risk of developing metastatic disease and in determining the optimal duration of therapy. Both areas require further clinical data.

In conclusion. tamoxifen adjuvant monotherapy has a low cost-utility ratio in postmenopausal women with node-positive, estrogen receptor-positive breast cancer. Combined therapy in the same patient group has a high cost-utility ratio compared with no therapy but quality-of-life and patient preference data suggest that the costs may be justified. Firm conclusions relating to the use of the drug in other patient subgroups and the optimal duration of therapy await further research.

Disease Considerations

According to recent statistics in the US, 1 in 9 women will develop breast cancer, twice the risk recorded in 1940. This equates with approximately 175 500 new cases per annum in the US alone. While a number of risk factors for breast cancer have been identified. few are amenable to intervention. Thus, screening as a means of early detection, locoregional and adjuvant therapy are all used in the management of early breast cancer.

To date, only the direct costs of breast cancer have been evaluated. Estimates show wide variation. One analysis, using a longitudinal data source, estimated the lifetime direct costs of breast cancer to be $US36 926 per patient (1984 dollars). Indirect costs are thought to be around 2 to 2.6 times greater than direct costs in patients with cancer.

As with other cancers. breast cancer has a massive effect on patient quality of life. Patients not only must come to terms with the diagnosis of breast cancer, but also with all the stages of treatment (surgery, radiation therapy and adjuvant therapy). Psychosocial stress experienced by the patient can extend to both partner and family. Fear of recurrence is often a primary concern among those with breast cancer. In the advanced stage of the disease, the patient experiences loss of independence, physical symptoms and a progressively compromised quality of life.

Therapeutic Efficacy and Tolerability

The recent overview conducted by the Early Breast Cancer Trialis’ Collaborative Group (EBCTCG) provides strong evidence that tamoxifen adjuvant therapy improves both disease-free survival and overall survival in women with early breast cancer. Treatment effects are greatest in patients with node-positive disease, those aged over 50 years, and those with estrogen receptor-positive breast cancer. From data generated from individual clinical trials and the EBCTCG overview, tamoxifen is now recommended for adjuvant use in postmenopausal women with early breast cancer, and particularly in those with node-positive, estrogen receptor-positive disease. importantly, in patients aged from 50 to 69 years, the efficacy of combined chemotherapy and tamoxifen exceeded that of either treatment modality alone.

Overall, tamoxifen has a favourable tolerability profile. The most common adverse events associated with tamoxifen treatment are hot flushes, and vaginal bleeding or discharge. Three to 4% of patients withdraw from treatment as a result of adverse events. With the use of increasingly prolonged regimens of tamoxifen, the long term effects of the drug require further investigation. Of concern is the association of tamoxifen with the development of endometrial, ovarian and liver cancers, and thromboembolic complications. Conversely, there are data which suggest that tamoxifen has possible beneficial effects on bone mineral density and cardiovascular risk factors in women.

Quality-of-Life Considerations

Preliminary data concerning Quality of life in patients treated with tamoxifen arc available. In postmenopausal women with node-positive breast cancer, tamoxifen combined with chemotherapy was superior in terms of both Time Without Symptoms and Toxicity (TWiST) and quality-adjusted TWiST (Q-TWiST) to tamoxifen plus prednisone, which in turn was superior to no treatment. However. the fact that tamoxifen was coadministered with prednisone confounded interpretation of the results.

Preliminary results after 15 months of an ongoing study using patient-derived quality-of-life data assessed with the Perceived Adjustment to Chronic Illness Scale. suggest that patients with stage II breast cancer receiving tamoxifen monotherapy fare better at most assessment months than those receiving tamoxifen combined with chemotherapy. A Q-TWiST analysis is required to determine if the greater effort to cope with the disease for patients receiving combined tamoxifen and chemotherapy could be balanced by an improved quality of life related to delayed disease recurrence and improved survival.

Only one study which incorporated a quality-of-life component in patients with node-negative breast cancer has been performed. While overall quality-of-life scores did not differ between patients treated with tamoxifen or placebo, it was suggested that persistent vasomotor symptoms among patients receiving tamoxifen could have an adverse effect on long term compliance.

Pharmacoeconomic Analysis

To date, 2 preliminary pharmacoeconomic evaluations involving the use of tamoxifen in postmenopausal women with node-positive breast cancer have been performed. In the first study, savings of $Can2247 per patient (1987 dollars) were realised as a result of improved disease-free survival after at least 8 year’ follow-up compared with no treatment.

In the second study, data generated from a decision-analysis model indicated that a 5-year regimen of tamoxifen had a favourable incremental cost-utility ratio [$US6000 per additional quality-adjusted life-year (QALY), 1989 dollars] compared with no therapy. The estimated incremental cost-utility ratio of adding chemotherapy to tamoxifen was $US58 000 per additional QAL Y, assuming that the addition of chemotherapy reduced the relapse rate by a further 19% than did tamoxifen alone. The cost-utility ratio was sensitive to the degree of efficacy assigned to the combined regimen. and ranged from $USI9 400 to $US420 000 per additional QALY (1989 dollars) in best and worst case scenarios, respectively.

In the most recent application of the same decision-analysis model, tamoxifen had a low incremental cost-utility ratio ($US4330 to $US11 440 per additional QALY, 1989 dollars) in premenopausal women with receptor-positive tumours. Chemotherapy gave added benefit over tamoxifen again at a low incremental cost-utility ratio ($US9230 to $US11 370 per additional QALY). In this context it is likely that chemotherapy will be favoured over tamoxifen. However, if administered as part of a combined regimen, tamoxifen offered small extra benefits over those seen with chemotherapy alone at favourable cost utility ($US14 750 to $US33 100 per additional QALY).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Aaronson NK. Assessing the quality of life of patients in cancer clinical trials: common problems and common sense solutions. European Journal of Cancer 28A (8/9): 1304–1307, 1992

    Article  Google Scholar 

  • Aaronson NK. Ahmedzai S, Bergman B, Bullinacr M, Cull A. et aI. The European Organization for Research and treatment of Cancer QLQ–C30: a quality–of–life instrument for use in international clinical trials in oncology. Journal of the National Cancer Institute 85 (5): 36S–376, 1993

    Article  Google Scholar 

  • Aaronson NK, Ahmedzai S, Bullinger M, Crabeels D, Estapé J, et al. The EORTC core quality–of–life questionnaire: interim results of an international field study. In Osoba (Ed.) Effect of cancer on quality of cancer on quality of life. pp. 185-203, Boca Raton, CRC Press, 1991

  • Aaronson NK, Calais da Silva F, de Voogt HJ. Subjective response criteria and quality of life. EORTC Genitourinary Group Monograph 5: Progress and Controversies in oncological Urology 2: 261–273, 1988

    Google Scholar 

  • 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 (4): 1132–1135, 1990

    Article  PubMed  CAS  Google Scholar 

  • Baker MS, Kessler LG, Urban N, Smucker RC. Estimaiting the treatment cost of breast and lung cancer. Medical Care 29 (1): 40–49, 1991

    Article  PubMed  CAS  Google Scholar 

  • Barofsky I, Sugarbaker PH. Cancer. In Spilker (Ed.) Quality of life assessments in clinical trials. pp. 419-440, Raven Press, New York, 1990

    Google Scholar 

  • Belanger D, Moore M, Tannock I. How American oncologists treat breast cancer; an assessment of the influence of clinical trials. Journal of Clinical Oncology 9: 7–16, 1991

    PubMed  CAS  Google Scholar 

  • Boccardo F, Guarneri D, Rubagotti A, Casertelli GL, Bentivoglio G. et al. Endocrine effects of tamoxifen in post menopausal breast cancer patients. Tumori 70: 61–68, 1984

    PubMed  CAS  Google Scholar 

  • Bonadonna G. Evolving concepts in the systemic adjuvant treatment of breast cancer. Perspectives in Cancer Research 51: 2127–2137, 1992

    Google Scholar 

  • Brown ML. The national economic burden of cancer: an update. Journal of the National Cancer Institute 82 (23): 1811–1814, 1990

    Article  PubMed  CAS  Google Scholar 

  • Brunner KW. Adjuvant therapies in breast cancer and quality of life: a critical review of the TWIST concept. Recent Results in Cancer Research 115: 239–243, 1989

    Article  PubMed  CAS  Google Scholar 

  • Buckley MMT, Goa KL. Tamoxifen: a reappraisal of its pharmacodynamic and pharmacokinetic properties, and the therapeutic use. Drugs 37: 451–490, 1989

    Article  PubMed  CAS  Google Scholar 

  • Butta A, Maclennan K, Flanders KC, Sacks NPM, Smith I, et al. Induction of transforming growth factor β in human breast cancer in vivo following tamoxifen treatment. Cancer Research 52: 4261–4264, 1992

    PubMed  CAS  Google Scholar 

  • Carter AP, Thompson RS, Bourdeau RV, Andenes J, Muslin H, et al. A clinically effective breast cancer screening program canbe cost–effective too. Preventive Medicine 16: 19–34, 1987

    Article  PubMed  CAS  Google Scholar 

  • Cassileth BR. Principles of quality of life assessment in cancer chemotherapy. Pharmacoeconomics 2 (4): 279–284, 1992

    Article  PubMed  CAS  Google Scholar 

  • Catherino WH, Jordan VC. A risk benefit assessment of tamoxifen therapy. Drug Safety 8 (5): 381–397, 1993

    Article  PubMed  CAS  Google Scholar 

  • Cella DF, Tulsky DS, Gray G, Sarafian B, Linn E. et al. The functional assessment of cancer therapy scale: development and validation of the general measure. Journal of Clinical Oncology 11: 570–579, 1993

    PubMed  CAS  Google Scholar 

  • Coates AS, Simes RJ. Patient assessment of adjuvant treatment in operable breast cancer. In Williams (Ed.) Introducing new treatments for cancer; practical, ethical and legal problems, pp.447-458 John Wiley, London, 1992

    Google Scholar 

  • Coyle D, Tolley K. Discounting of health benefits in the pharmacoeconomic analysis of drug therapies; an issue for debate? Pharmacoeconomics 2 (2): 153–162, 1992

    Article  PubMed  CAS  Google Scholar 

  • Cuzick J, Allen D, Baum M, Barett J, Clark G, et al. Long term effects of Tamoxifen: biological effects of tamoxifen working party. European Joumal of Cancer 29 (1): 15–21, 1993

    Article  Google Scholar 

  • Davidson NE. Tamoxifen–panacea or Pandora’s box? New England Journal of Medicine 326 (13): 885–886, 1992

    Article  PubMed  CAS  Google Scholar 

  • de Koning HJ, van Ineveld BM, de Haes JCJM, van Oortmarssen GJ, Klijn JGM, et al. Advanced breast cancer and its prevention by screening. British Journal of Cancer 65: 950–955, 1992

    Article  PubMed  Google Scholar 

  • Delrio G, De Placido S, Pagliarulo C, d’Istria M, Frasano S, et al. Hypothalamic–pituitary–ovarian axis in Women with operable breast cancer treated with adjuvant CMF and Tamoxifen. Tumori 72: 53–611, 1986

    PubMed  CAS  Google Scholar 

  • de Waard F. Endocrine aspects of cancer: an epidemiological approach. Journal of Steroid Biochemistry and Molecular Biology 40 (1-3): 15–19, 1991

    Article  PubMed  Google Scholar 

  • Dickson RB, Lippman ME. Estrogenic regulation of growth and polypeptide growth factor secretion in human breast carcinoma. Endocrine Reviews 8: 29–43, 1987

    Article  PubMed  CAS  Google Scholar 

  • Donovan K, Sanson-Fisher RW, Redman S. Measuring quality of life in cancer patients. Journal of Clinical Oncology 7: 959–968, 1989

    PubMed  CAS  Google Scholar 

  • Drummond MF, Stoddard Gt, Torrance GW. Methods for the economic evaluation of health care: Programmes. Oxford Medical Publications, Oxford, New York, Toronto, 1987

    Google Scholar 

  • 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

    Google Scholar 

  • Elixhauser A. Costs of breast cancer and the cost–effectiveness of breast cancer screening. International Journal of Technology Assessment in Health Care 7 (4): 604–615, 1991

    Article  PubMed  CAS  Google Scholar 

  • Epstein RJ. Does the breast cancer dollar make sense? European Journal of Cancer 28 (2-3): 486–491, 1992

    Article  PubMed  CAS  Google Scholar 

  • Fallowfield LJ. Quality of life measurement in breast cancer. Journal of the Royal Society of Medicine 86: 10–12, 1993

    PubMed  CAS  Google Scholar 

  • Feeny D, Labelle R, Torrance GW. Integrating economic evaluation and quality of life assessments. In Spilker (Ed.) Quality of life assessments in clinical trials, pp. 11-83, Raven Press, New York, 1990

    Google Scholar 

  • 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

    Article  PubMed  CAS  Google Scholar 

  • Finkler SA. The distinction between cost and charges. Annals of Internal Medicine 96: 102–109, 1982

    PubMed  CAS  Google Scholar 

  • Fornander T, Rutqvist LE, Cedermark B, Glass U, Mattsson A, et al. Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancer. Lancet 1: 117–120, 1989

    Article  PubMed  CAS  Google Scholar 

  • Fornander T, Rutqvist LE, Sjoberg HE, Blomqvist L, Mattsson A, et al. Long–term adjuvant tamoxifen in early breast cancer: effect on bone mineral density in postmenopausal women. Journal of Clinical Oncolo 8: 1019–1024, 1990

    CAS  Google Scholar 

  • Freund DA, Dittus RS. Principles of pharmacoeconomic analysis of drug therapy. Pharmacoeconomics 1 (1): 20–32, 1992

    Article  PubMed  CAS  Google Scholar 

  • Fugh-Berman A, Epstein S. Tamoxifen: disease prevention or disease substitution? Lancet 340: 1141–1145, 1992

    Article  Google Scholar 

  • Furr BJ, Jordan VC. The pharmacology and clinical uses of tamoxifen. Pharmacology and Therapeutics 25: 127–205, 1984

    Article  PubMed  CAS  Google Scholar 

  • Ganz PA, Coscarelli Schag CA, Cheng H-L. Assessing the quality of life–a study in newly diagnosed breast cancer patients. Journal of Cinical Epidemiology 43 (1): 75–86, 1990

    Article  CAS  Google Scholar 

  • Gelber RD, Coates AS, Goldhirsch A. Adjuvant treatment for breast cancer: the overview. Ovarian ablation, chemotherapy, and tamoxifen all work. British Medical Journal 304: 859–860, 1990

    Article  Google Scholar 

  • Gelber RD, Goldhirsch A. A new endpoint for the assessment of adjuvant therapy in postmenopausal women with operable breast cancer. Journal of Clinical Oncology 4: 1772–1779, 1986

    PubMed  CAS  Google Scholar 

  • Gelber RD, Goldhirsch A. Alternative methods for describing treatment benefit including Quality–of–life considerations. In Goldhirsch A (Ed.) European School of Oncology. ESO Monograph Series, 1990. Endocrine therapy of breast cancer, 87–97, 1990

    Google Scholar 

  • Gelber RD, Goldhirsch A, Cavalli F. Quality of life adjusted evaluation of adjuvant therapies for operable breast cancer. Annals of Internal Medicine 114 (8): 621–618, 1991

    PubMed  CAS  Google Scholar 

  • Gelber RD, Goldhirsch A, Hurny C, Bernhard J, Simes RJ. Quality of life in clinical trials of adjuvant therapies. Journal of National Cancer Institute Monograph 11: 127–135, 1992

    Google Scholar 

  • Glick JH. Adjuvant therapy for node–negative breast cancer a proactive view. Important Advances in Oncology: 183–197, 1990

    Google Scholar 

  • Glick JH, Gelber RD, Goldhirsch A, Senn HJ. Adjuvant therapy of primary breast cancer. 4th International Conference on Adjuvant Therapy of Primary Breast Cancer, St Gallen, Switzerland. Annals of Oncology 3: 801–807, 1992

    PubMed  CAS  Google Scholar 

  • Goldhirsch A, Gelber RD, Castiglione M. Adjuvant therapy of breast cancer. European Journal of Cancer 27 (3): 389–399, 1991

    Article  PubMed  CAS  Google Scholar 

  • Goldhirsch A, Gelber RD, Simes RJ, Glasziou P, Coates AS. Costs and benefits of adjuvant therapy in breast cancer; a quality adjusted survival analysis. Journal of Clinical Oncology 7: 36–44, 1989

    PubMed  CAS  Google Scholar 

  • Goldman L. Cost awareness in medicine. In Wilson et al. (Eds) Harrison’s principles of internal medicine, 12th (International)ed., Vol. 1. pp. 11-16, McGraw Hill, USA, 1991

  • Gotfredsen A, Christiansen C, Palshoft T. The effect of tamoxifen on bone mineral content in premenopausal women with breastcancer. Cancer 53: 853–857, 1984

    Google Scholar 

  • Hartunian NS, Smart CN, Thompson MS. The incidence and economic costs of cancer, motor vehicle injuries, coronary heart disease and stroke: a comparative analysis. American Journal of Public Health 70 (5): 1249–1260, 1980

    Article  PubMed  CAS  Google Scholar 

  • Heel RC, Brogden RN, Speight TM, Avery GS. Tamoxifen: a review of its pharmacological properties and therapeutic use in the treatment of breast cancer. Drugs 16: 1–24, 1978

    Article  PubMed  CAS  Google Scholar 

  • Helgason S, Wilking N, Carlstrom K, Damber M–G, von Schoultz B. A comparative study of the estrogenic effects of tamoxifen and 17β-estradiol in postmenopausal women. Journal of Cinical Endocrinology and Metabolism 54: 404–408, 1982

    Article  CAS  Google Scholar 

  • Henderson BE, Ross RK, Pike MC. Hormonal chemoprevention of cancer in women. Science 259: 633–638, 1993

    Article  PubMed  CAS  Google Scholar 

  • Henderson IC. Adjuvant therapy for node–negative breast cancer; a cautious interpretation. Important Advances in Oncology: 199–216, 1990

    Google Scholar 

  • Henderon M. Current approaches to breast cancer prevention. Science 259: 630–631, 1993

    Article  Google Scholar 

  • Hillner BE, Smith TJ. Efficacy and cost effectiveness of adjuvant chemotherapy in women with node–negative breast cancer: a decision–analysis model. New England Journal of Medicine 324: 160–168, 1991

    Article  PubMed  CAS  Google Scholar 

  • Hillner BE, Smith TJ. Estimating the efficacy and cost–effcctiveness of tamoxifen (TAM) versus TAM plus adjuvant chemotheraphyin post–menopausal node–positive breast cancer; a decision–analysis model. Proceedings of the American Society of Clinical Oncology 11, March 1992. Abstract no. 46. p. 55. 1991

    Google Scholar 

  • Hillner BE, Smith TJ. Should women with node–negative breast cancer receive adjuvant chemotherapy: insights from a decision–analysis model. Breast Cancer Research and Treatment 23: 17–27, 1992

    Article  PubMed  CAS  Google Scholar 

  • Hoskin PJ, Ashley S, Yarnold JR. Changes in body weight after treatment for breast cancer and the effect tamoxifen. British Journal of Cancer 62 (Suppl. 11): 26, 1990

    Google Scholar 

  • Hoskin PJ, Ashley S, Yarnold JR. Weight gain after primary surgery for breast cancer–effect of tamoxifen. Breast Cancer Research and Treatment 22: 119–132, 1992

    Article  Google Scholar 

  • Hurley SF, Huggins RM, Snyder RD, Bishop JF. The cost of breast cancer recurrences. British Journal of Cancer 65: 449–455, 1992

    Article  PubMed  CAS  Google Scholar 

  • Hürny C. Critical review of quality of life: psychosocial aspects of adjuvant therapy in breast cancer. Recent Results in Cancer Research 115: 279–282, 1989

    Article  PubMed  Google Scholar 

  • Hürny C, Bernhard J, Gelber RD, Coates A, Castiglione M. et al. Quality of life measures for patients receiving adjuvant therapy for breast cancer: an international trial. European Journal of Cancer 28 (1): 118–124, 1992

    Article  PubMed  Google Scholar 

  • Ingram D. Tamoxifen use, oestrogen binding and serrum lipids in postmenopausal women with breast cancer. Australia and New Zealand Journal of Surgery 60: 673–675, 1990

    Article  CAS  Google Scholar 

  • Irvine D, Brown B, Crooks D, Roberts J, Browne G. Psychosocial adjustment in women with breast cancer. Cancer 67: 1097–1117, 1991

    Article  PubMed  CAS  Google Scholar 

  • Jordan VC. The role of tamoxifen in the treatment and prevention of breast cancer. In Ozols et al. (Eds) Current problems in cancer, Vol. 16. Mosby–Year Book, Missouri, USA, 1992

  • Jordan VC, Fritz NF, Langan-Fahey S, Thompson M, Tormey DC. Alteration of endocrine parameters in premenopausalwomen with breast cancer during long–term adjuvant therapy with tamoxifen as the single agent. Journal of the National Cancer institute 83 (20): 1488–1491, 1991

    Article  PubMed  CAS  Google Scholar 

  • Jordan VC, Fritz NF, Tormey DC. Endocrine effects of adjuvant chemotherapy and long–term tamoxifen administration on node–positive patients with breast cancer. Cancer Research 47: 624–630, 1987

    PubMed  CAS  Google Scholar 

  • Jordan VC, Fritz NF, Tormey DC. Long–term adjuvant therapy with tamoxifen: effects of sex hormone binding globulin and antithrombin III. Cancer Research 47: 4517–4519, 1987

    PubMed  CAS  Google Scholar 

  • Jordan VC, Murphy CS. Endocrine phannacology of antiestrogens as antitumor agents. Endocrine Review 11 (4): 578–609, 1990

    Article  CAS  Google Scholar 

  • Jordan VC, Wolf MF, Mirecki DM, Whitford D, Welshons WV, et al. Honnone receptor assays: clinical usefulness in the management of carcinoma of the breast. Critical Reviews in Cinical and Laboratory Science 26: 97–152, 1988

    Article  CAS  Google Scholar 

  • Kelsey JL, Gammon MD. The epidemiology of breast cancer. CA–Cancer Journal for Clinicians 41 (3): 146–165, 1991

    Article  CAS  Google Scholar 

  • Lahti E, Blanco G, Kauppila A, Apaja-Sakkinen M, Taskinen PJ, et al. Endometrial changes in postmenopausal breast cancer patients receiving tamoxifen. Obstetrics and Gynecology 81 (1): 660–664, 1993

    PubMed  CAS  Google Scholar 

  • Levine MN, Guyatt GH, Gent M, De Pauw S, Goodyear MO, et al. Quality of life in stage II breast cancer: an instrument for clinical trials. Journal of Clinical Oncology 6: 1798–1810, 1998

    Google Scholar 

  • Lønning PE, Hall K, Aakvaag A, Lien EA. Influence of tamoxifen on plasma levels of insulin–like growth factor I an insulin–likegrowth factor binding protein I in breast cancer patients. Cancer Research 52 (17), 4719–4723, 1992

    PubMed  Google Scholar 

  • Lønning PE, Lien EA, Lundgren S, Kvinnsland S. Clinical pharmacokinetics of endocrine agents used in advanced breast cancer. Clinical Pharmacokinetics 22 (5): 327–358, 1992

    Article  PubMed  Google Scholar 

  • Love N. Why patients delay seeking care for cancer symptoms: what you can do about it. Cancer Evaluation 89 (4): 151–158, 1991

    CAS  Google Scholar 

  • Love RR, Cameron L, Connell BL, Leventhal H. Symptoms associated with tamoxifen treatment in postmenopausal women. Archives of lnternal Medicine 151: 1842–1847, 1991

    Article  CAS  Google Scholar 

  • Love RR, Leventhal H, Easterling DV, Nerenz DR. Side effects and emotional distress during cancer chemotherapy. Cancer 63: 604–612, 1989

    Article  PubMed  CAS  Google Scholar 

  • 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: 851–856, 1992

    Article  Google Scholar 

  • Love RR, Newcomb PA, Wiebe DA, Surawiez TS, Jordan VC, et al. Effects of tamoxifen therapy on lipid and lipoprotein levels in postmenopausal patients with node–negative breast cancer. Journal ofthe National Cancer Institute 82: 1327–1332, 1990

    Article  CAS  Google Scholar 

  • Love RR, Surawiez TS, Williams EC. Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifentherapy. Archives of Internal Medicine 151: 317–320, 1992

    Article  Google Scholar 

  • Ludwig Breast Cancer Study Group. Randomised trial of chemoendocrine therapy, endocrine therapy, and mastectomy alonein postmenopausal patients with operable breast cancer and axillary node metastasis. Lancet 1: 1256–1260, 1984

    Google Scholar 

  • Maguire P. Breast conservation versus mastectomy: psychological considerations. Seminars in Surgical Oncology 1: 137–144, 1989

    Article  Google Scholar 

  • Maguire P, Selby P. Assessing quality of life in cancer patients. British Journal of Cancer 60: 437–440, 1989

    Article  PubMed  CAS  Google Scholar 

  • Maguire P, Brooke M, Tait A. Thomas C, Sellwood R. The effect of counselling on physical disability and social recovery after mastectomy. Clinical Oncology 9: 319–324, 1983

    PubMed  CAS  Google Scholar 

  • Magriples U, Naftolin F, Schwartz PE, Carcangiu ML. High–grade endometrial carcinoma in tamoxifen–treated breast cancer patients. Journal of Clinical Oncology 11 (3): 485–490, 1993

    PubMed  CAS  Google Scholar 

  • Malfetano JH. Tamoxifen–associated endometrial carcinoma in postmenopausal breast cancer patients. Gynecologic Oncology 39: 82–84, 1990

    Article  PubMed  CAS  Google Scholar 

  • Marshall E. Search for a killer: focus shifts from fat to hormones. Science 259: 618–621, 1993

    Article  PubMed  CAS  Google Scholar 

  • Mason J, Drummond M, Torrance G. Some guidelines on the use of cost effectiveness league tables. British Medical Journal 306: 570–572, 1993

    Article  PubMed  CAS  Google Scholar 

  • Massie MJ, Holland JC. Psychological reactions to breast cancer in the pre–and post–surgical treatment period. Seminars in Surgical Oncology 7: 320–325, 1991

    Article  PubMed  CAS  Google Scholar 

  • 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 (4): 207–208, 1990

    PubMed  CAS  Google Scholar 

  • Maynard A. Developing the health care market. Economic Journal 101: 1277–1286, 1991

    Article  Google Scholar 

  • McCarthy M, Bore J. Treatment of breast cancer in two teaching hospitals: a comparison with consensus guidelines. European Journal of Cancer 27 (5): 579–582, 1991

    Article  PubMed  CAS  Google Scholar 

  • McDonald CC, Stewart HJ. Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. British Medical Journal 303: 435–437, 1991

    Article  PubMed  CAS  Google Scholar 

  • McEvoy MD, McCorkle R. Quality of life issues in patients with disseminated breast cancer. Cancer 66 (6): 1416–1421, 1990

    Article  PubMed  CAS  Google Scholar 

  • McGee RF, White CH. Helping employees and families cope with breast cancer treatment. American Association of Occupational Health Nurses Jourrnal 37 (5): 178–185, 1989

    CAS  Google Scholar 

  • McGuire WL, Clark GM. Prognostic factors and treatment decisions in auxillary–node–neptive breast cancer. New England Journal of Medicine 326: 1756–1761, 1992

    Article  PubMed  CAS  Google Scholar 

  • Mettlin C. Breast cancer risk factors: contributions to planning breast cancer control. Cancer 69: 1904–1910, 1992

    Article  PubMed  CAS  Google Scholar 

  • Meyerowitz BE. Psychosocial correlates of breast cancer and its treatments. Psychological Bulletin 87 (1): 108–131, 1980

    Article  PubMed  CAS  Google Scholar 

  • Mignotte H, Sasco AJ, Lasset C, Saez S, Rivoire M. Adjuvant therapy by tamoxifen for breast cancer and endometrium carcinoma. Bulletin du Cancer 79: 969–977, 1992

    PubMed  CAS  Google Scholar 

  • Mignotte M, Robin JY, Saez S, Rivoire M. Adjuvant therapy by tamoxifen for breast cancer and endometrial cancer. Abstract no. 757. European Journal of Cancer 27 (Suppl. 2): 5128, 1991

    Google Scholar 

  • Moinpour C, Feigl P, Metch B, Hayden KA, Meyskens Jr FL. et al. Quality of life end points in cancer clinical trials: review and recommendations. Journal of the National Cancer Institute 81: 485–495, 1989

    Article  PubMed  CAS  Google Scholar 

  • Morris JN, Sherwood S. Quality of life of cancer patients at different stages in the disease trajectory. Journal of Chronic Disease 40 (6): 545–553, 1987

    Article  CAS  Google Scholar 

  • NIH Consensus Conference. Adjuvant therapy for breast cancer. Journal of the American Medical Association 254: 3461–3463, 1985

    Article  Google Scholar 

  • NIH Consensus Panel. Treatment of early–stage breast cancer. Journal of the American Medical Association 265: 391–395, 1991

    Article  Google Scholar 

  • Nemoto T, Vana J, Bedwani RN, Baker HW, McGregor FH, Et al. Management and survival of female breast cancer. Results of a national survey by the American College of Surgeons. Cancer 45: 2917–2924, 1980

    Article  PubMed  CAS  Google Scholar 

  • Neven P, de Muylder X, van Belle Y, Vanderick G, De Muylder E. Tamoxifen and the uterus and endometrium. Lancet 1: 375, 1989

    Article  PubMed  CAS  Google Scholar 

  • Northouse LL, Cracchiolo-Caraway A, Appel CP. Psychologic consequences of breast on partner and family. Seminars in Oncology Nursing 7 (3): 216–223, 1991

    Article  PubMed  CAS  Google Scholar 

  • O’Brian CA, Housey GM, Weinstein IB. Specific and direct binding of protein kinase C to an immobilized tamoxifen analogue. Cancer Research 48: 3626–3629, 1988

    PubMed  Google Scholar 

  • O’Brian CA, Liskamp R, Solomon DH, Weinstein IB. Inhibition of protein kinase C by tamoxifen. Cancer Research 45: 2462–2465, 1985

    PubMed  Google Scholar 

  • O’Brian CA, Liskamp R, Solomon DH, Weinstein IB. Triphenylethylenes: a new class of protein kinase C inhibitors. Journal of the National Cancer Institute 76: 1243–1246, 1986

    PubMed  Google Scholar 

  • O’Reilly SM, Richards MA. Node negative breast cancer: adjuvant chemotherapy should probably be reserved for patients at high risk of relapse. British Medical Journal 300: 346–348, 1990

    Article  PubMed  Google Scholar 

  • Pollak M, Costantino J, Polychronakos C, Blauer S-A, Guyda H. et al. Effect of tamoxifen on serum insulin–like growth factor levels in stage I breast cancer patients. Journal of the National Cancer Institute 82 (21): 1693–1697, 1990

    Article  PubMed  CAS  Google Scholar 

  • Powles TJ. The case for clinical trials of tamoxifen for prevention of breast cancer. Lancet 340: 1145–1147, 1992

    Article  PubMed  CAS  Google Scholar 

  • 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 (6): 680–684, 1990

    Article  PubMed  CAS  Google Scholar 

  • Priestman TJ, Baum M. Evalution of quality of life in patients receiving treatment for advanced breast cancer. Lancet 1: 899–901, 1976

    Article  PubMed  CAS  Google Scholar 

  • Pritchard KI, Bruni T, Wodinsky H. An economic analysis of the use of adjuvant tamoxifen in postmenopausal women with positive axillary lymph nodes following surgery for breast cancer. 26th Annual Meeting of the American Society of Clinical Oncology, Washington, May 20-221990. Abstract no. 154, 41. 1990

    Google Scholar 

  • Pritchard KI, Meakin JW, Boyd NF, Ambus U, DeBoer G, et al. Adjuvant tamoxifen in postmenopausal women with axillary node positive breast cancer: an update. Proceedings of American Society of Clinical Oncology. Abstract no. 238, p. 61, 1987

  • Reddel RR, Murphy LC, Sutherland RL. Effects of biologically active metabolites of tamoxifen on the proliferation kinetics of MCF-7 human breast cancer cells in vitro. Cancer Research 43: 4618–4624, 1983

    PubMed  CAS  Google Scholar 

  • Reed MJ, Christodoulides A, Koistinen R, SeppäLä M, Teale JD, et al. The effect of endocrine therapy with medroxyprogesterone acetate, 4–hydroxyandrostencdione or tamoxifen on plasmaconcentrations of insulin–like growth factor (IGF)–I, IGF–II and IGFBP–I in women with advanced breast cancer. In ternational Journal of Cancer 12: 208–212, 1992

    Google Scholar 

  • Robinson SP, Jordan VC. Metabolism of steroid–modifying anticancer agents. Pharmacology and Therapeutics 36: 41–103, 1988

    Article  PubMed  CAS  Google Scholar 

  • Ryan WG. Wolter J, Bagdade SD. Apparent beneficial effects of tamoxifen on bone mineral content in patients with breast cancer: preliminary study. Osteoporosis International 12: 39–41, 1991

    Article  Google Scholar 

  • Schipper H, Clinch J, McMurray A, Levitt M. Measuring the quality of life of cancer patients: The Functional Living lndex–Cancer development and validation. Journal of Cinial Oncology 2 (5): 472–483, 1984

    CAS  Google Scholar 

  • Schover LR. The impact of breast cancer on sexuality, body image and intimate relationships. CA–A Cancer Journal for Clinicians 41 (2): 112–120, 1991

    Article  PubMed  CAS  Google Scholar 

  • Segna RA, Dottino PR, Deligdisch L, Cohen CJ. Tamoxifen and endometrial cancer. Mount Sinai Journal of Medicine 59 (5): 416–418, 1992

    PubMed  CAS  Google Scholar 

  • Selby PJ. Chapman J-AW, Etazadi-Amoli J, Dalley D, Boyde NF. The developement of a method for assessing the quality of life of cancer patients. British Journal of Cancer 50: 13–22, 1984

    Article  PubMed  CAS  Google Scholar 

  • Simes RJ, Cocker K, Glasziou P, Coates AS. Tattersall MHN. Costs and benefits of adjuvant chemotherapy for breast Cancer:an assessment of patient preferences. Proceedings of American Society of Clinical Oncology. Abstract no. 201, 52, 1989

    Google Scholar 

  • Slevin ML, Plant H, Lynch D, Drinkwater J, Gregory WM. Who should measure quality of life, the doctor of the patient? British Journal of Cancer 57: 109–112, 1988

    Article  PubMed  CAS  Google Scholar 

  • Smith TJ, Hillner BE. The efficacy and cost–effcetiveness of adjuvant therapy of early breast cancer in postmenopausal women. Journal of Clinical Oncology 11: 771–776, 1993

    PubMed  CAS  Google Scholar 

  • Sprangers MAG, Aaronson NK. The role of health care providers and significant others in evaluating the qualily of life of patients with chronic disease: a review. Journal of Clinical Epidemiology 45 (7): 743–760, 1992

    Article  PubMed  CAS  Google Scholar 

  • Steinberg J, Goodwin PJ. Alcohol and breast cancer risk–putting the current controversy into perspective. Breast Cancer Research and Treatment 19: 221–231, 1991

    Article  PubMed  CAS  Google Scholar 

  • Su H-D, Mazzei GJ, Vogler WR, Juo J-F. Effect of tamoxifen, a nonsteroidal antioestrogen, on phospholipids calcium–dependent protein kinase and phosphorylation of its endogenous substrateproteins from the rat brain and ovary. Biochemical Pharmacolocy 34: 3649–3653, 1985

    Article  CAS  Google Scholar 

  • Sutherland HJ, Lockwood GA, Boyd NF. Ratings of the importance of quality of life variables: therapeutic implications for patients with metastatic breast cancer. Journal of Cinical Epidemiology 43 (7): 661–66, 1990

    Article  CAS  Google Scholar 

  • Tannock IF. Management of breast and prostate cancer: how does quality of life enter the equation? Oncology 4 (5): 149–156, 1990

    PubMed  CAS  Google Scholar 

  • Tripathy D, Henderson IC. Systemic adjuvant therapy or breast cancer. Current Opinion in Oncology 4: 1041–1049, 1992

    Article  PubMed  CAS  Google Scholar 

  • Turken S, Siris E, Seldin D, Flaster E, Hyman G, et al. Effects of tamoxifen on spinal bone: density in women with breast cancer. Journal of the National Cancer Institute 81: 1086–1088, 1989

    Article  PubMed  CAS  Google Scholar 

  • Uziely B, Dotembus D, Brufman G, Lewin A, Catane R. et al. Abstract. The effect of tamoxifen on the endometrium. Proceeding of the American Association for Cancer Research 33: 281, 1992

    Google Scholar 

  • Vrbanec D, Reiner Z, Pezerovic DZ. Abstract. The effect of tamoxifen on serum lipid and lipoprotein levels. European Journal of Cancer 27 (Suppl. 2): 543, 1991

    Google Scholar 

  • Wainstock JM. Breast cancer: psychosocial consequences for the patient. Seminars in Oncology Nursing 7 (3): 207–215, 1991

    Article  PubMed  CAS  Google Scholar 

  • Wilkinson GS, Edgerton F, Wallace Jr HJ, Reese P, Patterson J, et al. Delay, Stage of disease and survival from breast cancer. Journal of Chronic Disease 32: 365–373, 1979

    Article  CAS  Google Scholar 

  • Wright CDP, Mansell RE, Gazet J-C, Compston JE. Effect of long term tamoxifen treatment on bone turnover in women with breast cancer. British Medical Journal 306: 429–30, 1993

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Various sections of the manuscript reviewed by: N.K. Aaronson, Psychosocial Research and Epidemiology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; G. Bonnadonna, Division of Medical Oncology, Instituto Nazionale Tumori, Milan, Italy; B.R. Cassileth, Behavioral Resources Corporation, Chapel Hill, North Carolina, USA; D. Coyle, University of York Centre for Health Economics, York, England; R.G. Gelber, Dana-Farber Cancer Institute, Division of Biostatistics, Boston, Massachusetts, USA; S. Green, Southwest Oncology Group Statistical Center, Fred Hutchinson Research Center, Seattle, Washington, USA; S.F. Hurley, Department of Biostatistics, School of Public Health and Community Medicine, University of Washington, Seatttle. Washington, USA; V.C Jordan, Department of Human Oncology, University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin, USA; R.R. Love, University of Wisconsin Clinical Cancer Center, Madison, Wisconsin, USA; C M . Moinpour, Southwest Oncology Group Statistical Center, Fred Hutchinson Research Center, Seattle, Washington, USA; M. Stockler, Department of Medical Oncology, Royal Prince Albert Hospital, Sydney. Australia.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bryson, H.M., Plosker, G.L. Tamoxifen. Pharmacoeconomics 4, 40–66 (1993). https://doi.org/10.2165/00019053-199304010-00006

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00019053-199304010-00006

Keywords

Navigation