© 2004 European Society for Medical Oncology
Original Article |
Tamoxifen-induced tissue factor pathway inhibitor reduction: a clue for an acquired thrombophilic state?
1 Institute of Oncology, Section of Medical Oncology, 2 Faculty of Medicine, Department of Internal Medicine, Section of Hematology, 3 Institute of Oncology, Department of Basic Oncology, Hacettepe University, Ankara, Turkey
* Correspondence to: I. Celik, Hacettepe University, Institute of Oncology, Sihhiye, Ankara 06100, Turkey. Tel: +90-312-305-2946; Fax: +90-312-309-2905; Email: onko-e{at}tr.net
Background: Current understanding of hemostatic systems enables us to better explore the enigmatic pathobiology of tamoxifen (TAM)-induced thrombotic diathesis. We have therefore aimed to assess the hemostatic changes in breast cancer patients receiving TAM on an adjuvant basis.
Patients and methods: The study population consisted of 43 female patients with hormone receptor-positive breast cancer who received TAM 20 mg/day as part of their adjuvant treatment. Mean age was 52±12 years (range 25–74). Twenty-one patients (49%) were premenopausal. Plasma samples were collected prior to and following 6 months of TAM therapy and were assayed for total tissue factor pathway inhibitor (TFPI), free TFPI, lipid-bound TFPI, thrombomodulin, D dimer, activated protein C resistance (APC res), factors VIIa, II, V, VII and X, and global fibrinolytic capacity (GFC).
Results: Median total TFPI decreased significantly from 48.5 ng/ml to 36.2 ng/ml (P=0.001), free TFPI from 10 to 7.6 ng/ml (P=0.001) and lipid-bound TFPI from 39.1 to 28.7 ng/ml (P=0.001). There were significant decreases in the levels of factor II (P=0.03), factor V (P=0.001), factor VII (P=0.06), thrombomodulin (P=0.01) and D dimer (P=0.001). However, APC res times were significantly prolonged (P=0.04). The remaining parameters that we have studied were not significantly affected.
Conclusion: Our findings suggest that TAM tends to activate the coagulation pathway by counteracting major molecules involved in coagulation inhibition, namely TFPI and TM. As reflected by unchanged GFC, the drug appears to impair the expected compensatory activation of the fibrinolytic system, which removes fibrin polymers resulting from coagulation activation.
Key words: breast cancer, hemostasis, hypercoagulability, tamoxifen, TFPI, venous thromboembolism