title: 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.
authors.affiliation: Department of Obstetrics and Gynaecology, Turku University Central Hospital, Turku, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Erkkola
authors.forename: L
authors.initials: L
authors.lastname: Mattila
authors.forename: T
authors.initials: T
authors.lastname: Powles
authors.forename: J
authors.initials: J
authors.lastname: Heikkinen
authors.forename: B
authors.initials: B
authors.lastname: Toivola
authors.forename: P
authors.initials: P
authors.lastname: Korhonen
authors.forename: M
authors.initials: M
authors.lastname: Mustonen
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D015519:Bone Density / Q000187:drug effects*; D001943:Breast Neoplasms / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D010865:Pilot Projects; D017698:Postmenopause; D017697:Premenopause; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D017312:Toremifene / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood*; D006113:United Kingdom / Q000453:epidemiology
chemical_list: D020845:Selective Estrogen Receptor Modulators; D014280:Triglycerides; D017312:Toremifene; D002784:Cholesterol