PB1502 - Hemostatic imbalance associated with tamoxifen in estrogen receptor-positive breast cancer patients: an observational study

Background: Estrogen receptor (ER)-positive breast cancer accounts for approximately 75% of all breast cancers. Tamoxifen, a selective estrogen receptor modulator (SERM) is the standard adjuvant treatment. Although better tolerated than aromatase inhibitors, tamoxifen increases the risk of venous thromboembolism (VTE) 1.4-fold. Compared to non-users of adjuvant therapy, this risk is 5-fold higher.

Aims: To assess the hemostatic imbalance induced by tamoxifen in adjuvant treatment of ER-positive breast cancer.

Methods: Twenty-five patients in remission from ER-positive breast cancer under adjuvant therapy with tamoxifen were included. 131 age- and BMI-matched healthy controls were included to define reference ranges (2.5th and 97.5th percentiles) of thrombin generation (TG) parameters. TG was performed in absence and in presence of exogenously added activated protein C (APC) to permit the calculation of the normalized APC sensitivity ratio (nAPCsr), a marker of APC resistance.

Results: Both in absence and in presence of APC, all TG parameters but the endogenous thrombin potential (ETP) (-APC) were significantly impacted by tamoxifen (p-value < 0.001). In absence of APC, regardless of TG parameters, at least 50% of results were out of the reference ranges, except for the ETP which lay 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-value < 0.0001).

Conclusion(s): This observational study showed that patients in remission from ER-positive breast cancer taking tamoxifen as adjuvant therapy had an altered thrombin generation, depicting a shift towards a hypercoagulable state 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.