Hemostatic imbalance induced by tamoxifen in estrogen receptor-positive breast cancer patients: An observational study

Marie Didembourg, Sara Reda, Johannes Oldenburg, Heiko Rühl, Jonathan Douxfils, Laure Morimont

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Estrogen receptor (ER)-positive (ER+) breast cancer accounts for approximately 75% of all breast cancers. Tamoxifen, a selective estrogen receptor modulator, is the standard adjuvant treatment. Although better tolerated than aromatase inhibitors, tamoxifen increases the risk of venous thromboembolism (VTE) 1.4-fold.
Aim: To assess the hemostatic imbalance induced by tamoxifen in adjuvant treatment of ER+ breast cancer.
Method: Twenty-five patients in remission from ER+ breast cancer under tamoxifen were included. One hundred and thirty one age- and BMI-matched healthy controls were included to establish reference ranges of thrombin generation assay (TGA) parameters. TGA was performed in the absence and presence of exogenous activated protein C (APC) to calculate the normalized APC sensitivity ratio (nAPCsr), a marker of APC resistance.
Results: All TG parameters except the endogenous thrombin potential (ETP) (APC) were significantly impacted by tamoxifen (p < 0.001). In absence of APC, regardless of TGA parameters, at least 50% of results were outside the reference ranges except
for ETP, which was above the upper reference limit in only two individuals. The most impacted parameter was the Peak Height with 52% (APC) and 80% (+APC) of results above the upper reference range limit, respectively. The nAPCsr was significantly higher in tamoxifen users (mean ± standard deviation = 3.18 ± 0.91) compared to the control group (2.19 ± 0.92, p < 0.0001).
Conclusion: This observational study showed that patients in remission from ER+ breast cancer taking tamoxifen had altered thrombin generation, as well as an acquired APC resistance. Moreover, this is the first study using the validated ETPbased APC resistance assay in tamoxifen-treated patients.
Translated title of the contributionDéséquilibre hémostatique induit par le tamoxifène chez les patientes atteintes d'un cancer du sein à récepteurs d'œstrogènes positifs : Une étude observationnelle
Original languageEnglish
Article number10.1111/ijlh.14242
Number of pages9
JournalInternational Journal of Laboratory Hematology
DOIs
Publication statusPublished - 15 Jan 2024

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