title: Effect of tamoxifen on venous thrombosis risk factors in women without cancer: the Breast Cancer Prevention Trial.
abstract: Tamoxifen reduces breast cancer incidence among healthy women, but is associated with an increased risk of venous thrombosis. We studied the 6 month effects of tamoxifen on venous thrombosis risk factors in women without cancer. One hundred and eleven women at one centre who were participants in a multicentre breast cancer prevention trial were randomized, in double-blind fashion, to receive 20 mg/d of tamoxifen or placebo. The activated protein C (APC) ratio and concentrations of antithrombin, protein C antigen, and total protein S were measured at baseline and 6 months of treatment. None of the factors changed over 6 months in placebo-treated women. Among tamoxifen-treated women, antithrombin and protein S, but not protein C or APC ratio were reduced. Sequential antithrombin concentrations with tamoxifen were 114% and 104% (P = 0.001 compared with placebo). Sequential protein S concentrations with tamoxifen were 18.42 and 17.30 micro g/ml (P = 0.02 compared with placebo). Reductions in antithrombin and protein S were greater in postmenopausal women, but did not differ by other risk factors for venous thrombosis, such as body mass index. Reductions of antithrombin and protein S, but not protein C or APC resistance, might relate to the increased risk of venous thrombosis associated with tamoxifen treatment.
authors.affiliation: Department of Medicine, University of Vermont, Burlington, VT, USA. mary.cushman@uvm.edu
authors.forename: Mary
authors.initials: M
authors.lastname: Cushman
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.forename: Edwin G
authors.initials: EG
authors.lastname: Bovill
authors.forename: D Lawrence
authors.initials: DL
authors.lastname: Wickerham
authors.forename: Lenore
authors.initials: L
authors.lastname: Buckley
authors.forename: John D
authors.initials: JD
authors.lastname: Roberts
authors.forename: David N
authors.initials: DN
authors.lastname: Krag
mesh_terms: D020016:Activated Protein C Resistance / Q000097:blood; D000991:Antithrombins / Q000032:analysis; D001780:Blood Coagulation Tests; D001943:Breast Neoplasms / Q000517:prevention & control*; D004311:Double-Blind Method; D020847:Estrogen Receptor Modulators / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008875:Middle Aged; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D012307:Risk Factors; D018709:Statistics, Nonparametric; D013629:Tamoxifen / Q000009:adverse effects* / Q000627:therapeutic use; D020246:Venous Thrombosis / Q000097:blood / Q000139:chemically induced*
chemical_list: D000991:Antithrombins; D020847:Estrogen Receptor Modulators; D011486:Protein C; D017293:Protein S; D013629:Tamoxifen