How do you manage endocrine therapy for premenopausal women with breast cancer who are heterozygous for factor V Leiden but have no history of thrombosis?

This is a difficult situation given that the literature is contradictory on this topic. Both tamoxifen and a factor V Leiden mutation independently increase risk of thromboembolic events. It is unclear whether, together, they would be additive in conferring risk of thrombosis. Dr. Cuzick wrote a very nice editorial on this topic (J Natl Cancer Inst, 2010 102(13):918-19). He outlines that in breast cancer primary prevention trials (like the NSABP P1 study and the IBIS-I trial), neither factor V Leiden nor prothrombin mutation carriers seemed to have excess risk of thrombosis on tamoxifen than controls without mutations. In other words, tamoxifen increased risk of thrombosis in patients on tamoxifen, but the mutations did not confer excess ri...