PB0912 - Evaluation of activated protein C resistance in women undergoing tamoxifen therapy: pilot study

Monday, July 11, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Marie Didembourg, MBS

PhD student
University of Namur, Department of Pharmacy
Namur, Namur, Belgium

Co-Author(s)

Jonathan Douxfils, PharmD, PhD

Prof.
University of Namur, Department of Pharmacy
Namur, Namur, Belgium
SR

Sara Reda

Dr. med.
Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn
Bonn, Nordrhein-Westfalen, Germany
HR

Heiko Rühl

Senior researcher
Institute of Experimental Haematology and Transfusion Medicine, University Hospital Bonn
Bonn, Nordrhein-Westfalen, Germany
Laure Morimont

PhD student
University of Namur, Department of Pharmacy, Namur,Belgium
Namur, Namur, Belgium

Background: Tamoxifen, a selective estrogen receptor modulator (SERM), is known to reduce hormono-dependent breast cancer recurrence but is associated with an increased risk of venous thromboembolism. As already demonstrated with oral contraceptives, compounds interacting with estrogen receptors can impact hemostasis and a resistance towards the activated protein C (APC) is now well described for combined oral contraceptive (COC). Nevertheless, the underlying mechanism of tamoxifen-induced procoagulable state remains unclear.

Aims: To assess APC resistance in women and men with hormono-dependent breast cancer undergoing tamoxifen therapy, using the validated ETP-based APC resistance assay.

Methods: Overall, 21 women and 2 men (mean age = 57) under active tamoxifen therapy were included. The ETP-based APC resistance assay was assessed on the CAT system, using ThromboScreen -TM (Diagnostica Stago, France) as triggering reagent in absence and in presence of exogenous APC. As several patients were on anticoagulant therapy, all samples were treated with the DP filter device to remove the impact of anticoagulation on thrombin generation. To estimate the influence of tamoxifen on the normalized APC sensitivity ratio (nAPCsr), results were compared to a historical reference cohort of 47 healthy individuals (19 women and 28 men; mean age = 24). The nAPCsr results stood between 0 to 10, with higher values representing a higher resistance towards APC.

Results: The mean nAPCsr ± SD of patients under tamoxifen therapy was 3.23 ± 0.93 (range: 1.31 to 4.9) which was significantly higher from the mean nAPCsr of the control group (1.04 ± 0.59 (range: 0.00 to 2.10)) (p-value < 0.001). This correspond to nAPCsr observed with second generation COC or factor V Leiden.

Conclusion(s): The nAPCsr values of patients undergoing tamoxifen therapy were significantly higher compared to healthy individuals, supporting APC resistance. Further analyses are needed to confirm the results of this pilot study.