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

Abstract

AbstractBackgroundEstrogen 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.AimTo assess the hemostatic imbalance induced by tamoxifen in adjuvant treatment of ER+ breast cancer.MethodTwenty‐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.ResultsAll 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).ConclusionThis 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 ETP‐based APC resistance assay in tamoxifen‐treated patients.