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(Circulation. 2005;111:650-656.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Effect of Tamoxifen on Venous Thromboembolic Events in a Breast Cancer Prevention Trial

Andrea Decensi, MD; Patrick Maisonneuve, PhD; Nicole Rotmensz, PhD; Donato Bettega, MD; Alberto Costa, MD; Virgilio Sacchini, MD; Alessandro Salvioni, MD; Roberto Travaglini, MD; Pasquale Oliviero, MD; Giuseppe D’Aiuto, MD; Marcella Gulisano, MD; Giacomo Gucciardo, MD; Marco Rosselli del Turco, MD; Maria Antonietta Pizzichetta, MD; Serafino Conforti, MD; Bernardo Bonanni, MD; Peter Boyle, PhD; Umberto Veronesi, MD, for the Italian Tamoxifen Study Group

From the Divisions of Chemoprevention (A.D., B.B.), Epidemiology and Biostatistics (P.M., N.R., P.B.), and Senology (V.S., U.V.), European Institute of Oncology, Milan, Italy; Department of Medical and Preventive Oncology (A.D.), Ospedali Galliera, Genoa, Italy; Ospedale Moriggia Pelascini (D.B.), Gravedona, Italy; and Fondazione Maugeri (A.C.), Pavia, Italy; Memorial Sloan-Kettering Cancer Center (V.S.), New York, NY; Centro Cardiologico Monzino (A.S.), Milan, Italy; Comitato Prevenzione Tumori (R.T.), Milan, Italy; Istituto Pascale (P.O., G.D.A.), Naples, Italy; Ospedale San Bortolo (M.G.), Vicenza, Italy; Ospedale San Camillo-Forlanini (G.G.), Rome, Italy; Centro Prevenzione Oncologica (M.R.T.), Florence, Italy; Centro di Riferimento Oncologico (M.A.P.), Aviano, Italy; and Ospedale Mariano Santo (S.C.), Cosenza, Italy.

Correspondence to Andrea Decensi, MD, European Institute of Oncology, via Ripamonti 435, 20141 Milan, Italy. E-mail andrea.decensi{at}ieo.it

Received April 6, 2004; revision received October 27, 2004; accepted November 3, 2004.

Background— Tamoxifen, a selective estrogen-receptor modulator, increases venous thromboembolic events (VTE), but the factors explaining this risk are unclear. Atherosclerosis may induce VTE, or the 2 conditions may share common risk factors. We assessed the effect of tamoxifen on VTE in a breast cancer prevention trial and studied its association with risk factors for VTE.

Methods and Results— The incidence of VTE was studied in 5408 hysterectomized women randomly assigned to tamoxifen 20 mg/d or placebo for 5 years. There were 28 VTEs on placebo and 44 on tamoxifen therapy (hazard ratio [HR]=1.63; 95% confidence interval [CI], 1.02 to 2.63), 80% of which were superficial phlebitis, accounting for all of the excess due to tamoxifen within 18 months from randomization. Compared with placebo, the risk of VTE on tamoxifen was higher in women aged 55 years or older, women with a body mass index 25 kg/m², elevated blood pressure, total cholesterol 250 mg/dL, current smoking, and a family history of coronary heart disease (CHD). Of the 685 women with a CHD risk score 5 who entered the trial, 1 in the placebo arm and 13 in the tamoxifen arm developed VTE (log-rank P=0.0013). In multivariate regression analysis, age 60 years, height 165 cm, and diastolic blood pressure 90 mm Hg had independent detrimental effects on VTE risk during tamoxifen therapy, whereas transdermal estrogen therapy concomitant with tamoxifen was not associated with any excess of VTE (HR=0.64; 95% CI, 0.23 to 1.82).

Conclusions— Women with conventional risk factors for atherosclerosis have a higher risk of VTE during tamoxifen therapy. This information should be incorporated into counseling women on its risk-benefit ratio, particularly in the prevention setting.

Key Words: prevention • veins • thrombosis • risk factors • trials

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