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Inherited and Acquired Risk Factors for Venous Thromboembolic Disease Among Women Taking Tamoxifen to Prevent Breast Cancer

Catherine Duggan, Kevin Marriott, Rob Edwards, Jack Cuzick

From the Department of Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Charterhouse Square; and the Haematology Department, St Mary’s National Health Service Trust, London, United Kingdom.

Address reprint requests to Jack Cuzick, PhD, Department of Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Charterhouse Square, London EC1M 6BQ, United Kingdom; e-mail: jack.cuzick{at}cancer.org.uk.

Purpose: Venous thromboembolism (VTE) is of particular concern in women receiving tamoxifen in a chemopreventive setting. We investigate the association between acquired and inherited risk factors for VTE in the International Breast Cancer Intervention Study (IBIS-I) trial of tamoxifen prophylaxis for women at increased risk of breast cancer.

Methods: We used a nested case-control study design to investigate the role of tamoxifen and acquired risk factors in the risk of developing a VTE.

Results: Tamoxifen was associated with a significantly increased risk of developing a major VTE (odds ratio [OR], 2.1; 95% CI, 1.1 to 4.1). Women who had surgery, immobilization, or fracture in the previous month had a greatly increased risk of developing a major VTE (OR, 4.7; 95% CI, 2.2 to 10.1). Prothrombin and factor V Leiden mutations were found exclusively among control women: factor V Leiden in eight of 159 control women (5.0%) and the prothrombin mutation in three control women (1.9%). Thirty-five women with a VTE and a blood sample were negative for these mutations. The upper one-sided 97.5% CI for the OR of having either mutation was 1.87. Being overweight, smoking, or taking hormone replacement therapy was not associated with VTE in this study, but the CIs were wide.

Conclusion: Tamoxifen and prior surgery, fracture, or immobilization were associated with a significantly increased risk of developing a VTE. Factor V Leiden and prothrombin mutations were not associated with thrombosis in this population.

Supported by Cancer Research United Kingdom.

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