The synthetic antiestrogen tamoxifen is demonstrating significant value as adjuvant therapy for female breast cancer. It is currently standard therapy for postmenopausal women with axillary node-positive, hormone- receptor-positive disease. Recent studies suggest it is also effective in increasing disease-free survival in both pre- and postmenopausal women with hormone-receptor-positive breast cancers without axillary node metastases. Data from several sources suggest that therapy of long duration is necessary to maintain control of micrometastatic disease. Major acute toxicity from tamoxifen is thought to be rare. However, because large and increasing numbers of women are taking tamoxifen for long periods, detailed data about its effect on other tissues are critical. The current proposal is designed to increase the scientific value of a single institution, double-blind, placebo-controlled, randomized toxicity study of tamoxifen in postmenopausal women with node-negative breast cancer. Study endpoints are: 1. Bone mineral content at the radius and lumbar spine measured by photon absorptiometry; 2. Plasma cholesterol, triglyceride and lipoprotein levels; 3. Coagulation proteins: antithrombin III, proteins C and S, and plasminogen; and 4. Calciotropic hormones: osteocalcin and 1,25-dihydroxyvitamin D. Planned accrual of 140 to this study has been completed. Limited interim analyses indicate that the very low drop out and high compliance rates should lead to excellent data addressing the impact of tamoxifen on the named endpoints. Support requested in this application will make possible a more comprehensive picture of tamoxifen's critical biological and clinical effects. The final year of study would be completed during the project period. Detailed analysis and consideration of the clinical implications and significance, and widespread dissemination of the findings would be the major focus of the project. It is expected that these analyses will define investigational directions for the future.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA050243-02
Application #
3194633
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Project Start
1989-09-29
Project End
1991-07-31
Budget Start
1990-08-01
Budget End
1991-07-31
Support Year
2
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Cameron, Linda D; Leventhal, Howard; Love, Richard R et al. (2002) Trait anxiety and tamoxifen effects on bone mineral density and sex hormone- binding globulin. Psychosom Med 64:612-20
Love, R R; Anker, G; Yang, Y et al. (1999) Serum homocysteine levels in postmenopausal breast cancer patients treated with tamoxifen. Cancer Lett 145:73-7
Love, R R (1995) Clinical review 70: Approaches to the prevention of breast cancer. J Clin Endocrinol Metab 80:1757-60
Mamby, C C; Love, R R; Lee, K E (1995) Thyroid function test changes with adjuvant tamoxifen therapy in postmenopausal women with breast cancer. J Clin Oncol 13:854-7
Love, R R (1994) Prevention of breast cancer in premenopausal women. J Natl Cancer Inst Monogr :61-5
Mamby, C C; Love, R R; Feyzi, J M (1994) Protein S and protein C level changes with adjuvant tamoxifen therapy in postmenopausal women. Breast Cancer Res Treat 30:311-4
Love, R R; Barden, H S; Mazess, R B et al. (1994) Effect of tamoxifen on lumbar spine bone mineral density in postmenopausal women after 5 years. Arch Intern Med 154:2585-8
Love, R R; Wiebe, D A; Feyzi, J M et al. (1994) Effects of tamoxifen on cardiovascular risk factors in postmenopausal women after 5 years of treatment. J Natl Cancer Inst 86:1534-9
Love, R R (1993) The National Surgical Adjuvant Breast Project (NSABP) Breast Cancer Prevention Trial revisited. Cancer Epidemiol Biomarkers Prev 2:403-7
Love, R R; Surawicz, T S; Williams, E C (1992) Antithrombin III level, fibrinogen level, and platelet count changes with adjuvant tamoxifen therapy. Arch Intern Med 152:317-20

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