© The Author 2006. Published by Oxford University Press.
ARTICLE |
Effect of Factor V Leiden and Prothrombin G20210
A Mutations on Thromboembolic Risk in the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial
Affiliations of authors: National Surgical Adjuvant Breast and Bowel Project Operations and Biostatistical Centers, Pittsburgh, PA (NA, JPC, JEG, DLW, NW); Baptist Medical Center, Jacksonville, FL (NA); Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA (JPC); Dana-Farber Cancer Institute, Boston, MA (JEG); School of Medicine, Yale University, New Haven, CT (NB); Allegheny General Hospital, Pittsburgh, PA (NW)
Correspondence to: Neil Abramson, MD, Baptist Cancer Institute, 3rd Floor, 1235 San Marco Blvd., University of Florida, Jacksonville, FL 32207-8554 (e-mail: abrm1h{at}bellsouth.net).
Background: In the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention Project (BCPT), tamoxifen use was associated with an increased relative risk for venous thromboembolic events, including deep vein thrombosis and pulmonary emboli, compared with placebo. However, the involvement of hypercoagulability factors in this association is unclear. Methods: To examine possible associations among the risk of venous thromboembolic events, tamoxifen use, and Factor V Leiden (FVL) and prothrombin G20210
[GenBank]
A (PT20210) mutations, which are involved in promoting blood coagulation, we used a nested, matched, case–control (1 : 4) design and compared women in the BCPT who had experienced venous thromboembolic events (n = 76) with women who did not (n = 295). FVL and PT20210 mutations were detected in genomic DNA that was isolated from blood samples collected at trial enrollment. Results: Venous thromboembolic events occurred in 28 women (deep vein thrombosis in 22 and pulmonary emboli in six) who were taking placebo and in 53 women (deep vein thrombosis in 35 and pulmonary emboli in 18) who were taking tamoxifen (relative risk = 1.90, 95% confidence interval = 1.18 to 3.12). Excessive risk for venous thromboembolic events was observed only in the first 36 months of therapy. There were no differences in age, smoking, and race between the groups, but women with venous thromboembolic events had a higher body mass index than women without (mean ± standard deviation, 30 kg/m2 ± 7.7 versus 27.1 ± 5.6; P<.001). FVL and/or PT20210 mutations were found in nine women (four on tamoxifen and five on placebo) with venous thromboembolic events and in 20 control subjects (nine on tamoxifen and 11 on placebo). No associations were found between risk of venous thromboembolic events and mutation status in either treatment group. Conclusions: Venous thromboembolic disease in the BCPT women is associated with tamoxifen use and body mass index, but not with FVL and PT20210 mutations. Screening women at risk for breast cancer for FVL and/or PT20210 appears to offer no benefit in determining the risk of tamoxifen-associated thromboembolic events.
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