Effect of tamoxifen on venous thrombosis risk factors in women without cancer: the Breast Cancer Prevention Trial
Effect of tamoxifen on venous thrombosis risk factors in women without cancer: the Breast Cancer Prevention Trial
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DOI：
10.1046/j.1365-2141.2003.03976.x
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发表时间：
2003-01-01
影响因子：
6.5
通讯作者：
Krag, DN
中科院分区：
文献类型：
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作者：
Cushman, M;Costantino, JP;Krag, DN
他莫昔芬可降低健康女性的乳腺癌发病率，但与静脉血栓形成风险增加有关。我们研究了他莫昔芬对非癌症妇女静脉血栓形成危险因素的6个月影响。在一个多中心乳腺癌预防试验中，111名妇女在一个中心以双盲方式随机接受20 mg/d的他莫昔芬或安慰剂。在基线和治疗6个月时测量活化蛋白C（APC）比率和抗凝血酶、蛋白C抗原和总蛋白S的浓度。在安慰剂治疗的女性中，这些因素在6个月内均未发生变化。在他莫昔芬治疗的妇女中，抗凝血酶和蛋白S，但不是蛋白C或APC的比例降低。序贯抗凝血酶浓度与他莫昔芬分别为114%和104%（P = 0.001与安慰剂相比）。连续蛋白S浓度与他莫昔芬为18.42和17.30 μ g/ml（P = 0.02与安慰剂相比）。抗凝血酶和蛋白S的减少在绝经后妇女中更大，但在静脉血栓形成的其他危险因素如体重指数方面没有差异。抗凝血酶和蛋白S的减少，而不是蛋白C或APC抵抗，可能与他莫昔芬治疗相关的静脉血栓形成风险增加有关。
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 mug/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.