Bone Mineral Density and Lipid Changes During 5 Years of Follow-up in a Study of Prevention of Breast Cancer with Toremifene in Healthy, High-risk Pre- and Post-menopausal Women

Abstract

A double-blind, randomised, placebo-controlled pilot study was initiated to evaluate the feasibility of chemoprevention with toremifene 60 mg/day in healthy women at high risk for breast cancer. Enrolment in the study was terminated earlier than planned because of slow patient accrual, although 13% of patients continued for 5 years. The revised efficacy outcomes were change in bone mineral density (BMD) from baseline at four skeletal sites, plus effects on serum lipids. In premenopausal women there was a trend for sustained increase in BMD during toremifene therapy after year 1 in lumbar spine. In postmenopausal women, toremifene had little or no effect on BMD trends. Levels of total and low-density lipoprotein (LDL) cholesterol were largely unchanged from baseline in premenopausal women treated with toremifene but were often slightly lower than in the placebo group during follow-up. Total and LDL cholesterol levels declined slightly from baseline in the postmenopausal women and were, at several points during the first 3 years, significantly lower than in the corresponding placebo group (p < 0.01). We conclude that: (a) assessment of toremifene 60 mg/day in chemoprevention will require further clinical trials; (b) toremifene 60 mg/day has no substantive negative effects on BMD in pre- or postmenopausal women and may exert a minor favourable influence (in particular, the effects of toremifene 60 mg/day on BMD in premenopausal women may make the drug an attractive alternative to tamoxifen 20 mg/day for that patient subset); (c) lipid effects of toremifene 60 mg/day are, at minimum, neutral and may be modestly favourable for reducing cardiovascular risk.

The effects of atamestane and toremifene alone and in combination compared with letrozole on bone, serum lipids and the uterus in an ovariectomized rat model

“…Our results confirmed that TOR has positive and beneficial effects on bone and lipid metabolism in as far as TOR significantly increased BMD, as well as significantly reduced the rise in serum cholesterol, LDL and TG induced by OVX. However, TOR had a significant stimulatory effect on uterine epithelium [26][27][28][29][30][31].…”

Toremifene in the treatment of breast cancer

“…Some beneficial effects on BMD have been observed in premenopausal women at high risk for developing breast cancer taking toremifene 60 mg as chemoprevention, therefore making an attractive alternative to tamoxifen. A double-blind, placebo-controlled pilot study in 259 healthy premenopausal and postmenopausal women at high risk for breast cancer found a trend for a sustained increase in lumbar spine BMD after one year of toremifene therapy in premenopausal women [58] .…”

Toremifene Improves Lipid Profiles in Men Receiving Androgen-Deprivation Therapy for Prostate Cancer: Interim Analysis of a Multicenter Phase III Study

“…11,17,18 In contrast, the various SERMs seem to differ in their effects on serum HDL cholesterol and triglycerides. In two of three randomized controlled trials in postmenopausal women, for example, toremifene significantly increased HDL cholesterol and decreased triglycerides compared with tamoxifen.…”

“…10 In an ongoing, multicenter, phase III study, 1,389 men receiving ADT for prostate cancer were assigned to receive either placebo or toremifene (80 mg/d) for 2 years. Toremifene significantly improved serum lipid profiles in postmenopausal women [11][12][13][14] but its effects on serum lipids in men are unknown. We now report the results of interim analysis to evaluate the effects of toremifene on serum lipids in men receiving ADT for prostate cancer.…”