Study Compares Effects of Antiestrogens on Bone and Lipids

SAN ANTONIO—Toremifene (Fareston), a recently approved anties-trogen, appears to have similar effects to those of tamoxifen (Nolvadex) on bone mineral density and potentially greater beneficial effects on serum lipoproteins in postmenopausal women with breast cancer, Tiina Saarto, MD, said at her poster presentation at the 20th Annual San Antonio Breast Cancer Symposium.

Previous research has shown that postmenopausal women who receive tamox-ifen obtain estrogen-like benefits, since the agent decreases bone mineral density and increases circulating lipids. Studies in postmenopausal women show that tamoxifen decreases total cholesterol and low-density lipoprotein (LDL) levels, but generally has no effect on high-density lipoprotein (HDL) and triglycerides.

Dr. Saarto and her colleagues at the University of Helsinki in Finland sought to determine whether toremifene—a triphenylethylene derivative with antitu-mor properties comparable to those of tamoxifen—also possesses similar anti-atherogenic properties.

Dr. Saarto’s group randomized 49 women with early-stage, node-positive breast cancer to receive either tamoxifen, 20 mg/day, or toremifene, 60 mg/day, orally for 3 years. Measurements of bone mineral density of the lumbar spine and femoral neck were taken at baseline and then at years 1 and 2, while lipids were measured at baseline and 1 year.

Analysis showed that toremifene and tamoxifen prevented bone loss in the lumbar spine and femoral neck with equal efficacy. Similarly, both agents significantly reduced total and LDL cholesterol levels, as well as apolipoprotein (apo) B levels, at the 1-year evaluation, with no significant between-group differences.

However, Dr. Saarto said, a very clear difference emerged in HDL changes between the two groups. Tamoxifen was associated with a 5% decrease in HDL whereas toremifene increased HDL by 14% (P =.001). As a result, the ratio of total cholesterol to HDL and the ratio of LDL to HDL decreased more in patients taking toremifene (P = .008) than in the tamoxifen group (P = .03).

Dr. Saarto stressed that due to the relatively small number of patients in this study, it will be necessary to reexamine this apparent effect of toremifene on HDL in a larger sample before any conclusions can be drawn.

Increased apo A-I levels and a subsequent increase in the ratio of apo A-I to apo A-II were observed only in the toremifene-treated group. Significant decreases in Lp(a) (lipoprotein a) levels occurred in both the tamoxifen and toremifene arms (34% and 41%, respectively). According to recent studies, Lp(a) may represent an independent risk factor for coronary heart disease, she said.

Dr. Saarto also noted that both drugs were associated with similar reductions in follicle-stimulating hormone and luteinizing hormone, and neither drug altered estradiol levels significantly.

The Finnish group concluded that, like tamoxifen, toremifene appears to exert an estrogen-like effect on bone mineral density. Further, she said, toremifene “possesses substantial antiatherogenic properties and could potentially improve the adverse lipoprotein levels associated with increased heart disease risk.”