Tamoxifen is being given as adjuvant therapy for breast cancer to greater numbers of women and for longer durations. Further, this hormone is under consideration as a chemosuppressive agent. To date, animal data have shown that tamoxifen acts as an antiresorptive agent and preserves bone, but published human studies have not demonstrated definitively this favorable effect. While tamoxifen appears to lower blood cholesterol levels, its impact on high density lipoprotein (HDL) cholesterol is uncertain. The Wisconsin Tamoxifen Study (WTS) (for an extension of which this is a proposal) was a randomized placebo-controlled 2-year toxicity study of tamoxifen 10 mg bid in 140 postmenopausal women with axillary node-negative breast cancer. In the WTS, after 2-years the rate of change in lumbar spine bone mineral density (BMD) was significantly different and preserved in tamoxifen-treated subjects (tamoxifen-treated women +0.61%/year; placebo-treated women -- -0.99%/year HDL lipoprotein cholesterol was minimally depressed by tamoxifen at early measurement times, but not at 18 and 24 months. The current proposal is to examine lumbar spine bone mineral density using dual photon absorptiometry, lipoproteins, and several other critical parameters, once, at 4-5 years from entry, in 2 groups of the WTS study participants available to study: 1) The 32 women (of 70) originally, randomized to tamoxifen treatment who continued this treatment for 4 years; and 2) 42 women (of 70) originally randomized to placebo treatment who continued not taking tamoxifen for 4 years. Analysis comparing BMD in these groups at baseline of the WTS and after 4 years will provide further refined data on the bone effects of tamoxifen which will allow more accurate prediction of its likely long term impact on fracture rates. The cholesterol HDL lipoprotein data will provide information on the long term impact of tamoxifen on heart disease endpoints.
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