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Differential impact of tamoxifen and aromatase inhibitors on thrombin generation: the prospective HEMOBREAST cohort

Published in Blood advances. 2022, vol. 6, no. 9, p. 2884-2892
Abstract Tamoxifen and aromatase inhibitors (AIs) are potent antitumoral agents against breast cancer. Tamoxifen increases the risk of venous thromboembolism (VTE), but the influence of AIs on the risk of VTE remains unclear. To inform clinical decisions, we evaluated associations of tamoxifen or AIs with changes of surrogate hemostatic biomarkers. This prospective cohort included 107 women with localized breast cancer starting tamoxifen (n = 42) or an AI (n = 65). Thrombin generation (CAT) its sensitivity to thrombomodulin (TM) or activated protein C (APC), and specific coagulation parameters, were measured before and 10-16 weeks after initiation of treatmen Compared with baseline, endogenous thrombin potential and thrombin peak increased in tamoxifen users (+86 nM × min; 95% confidence interval [CI], 30-142; and +33 nM; 95% CI, 21-45) but not in AI users (n = 65; +44 nM × min; 95% CI, −4 to 93; and +7 nM; 95% CI, −3 to 17). Normalized TM sensitivity ratios increased with tamoxifen (+0.26; 95% CI, 0.19-0.33y) but not with AI (+0.02; 95% CI, −0.03 to 0.07). Plasma levels of fibrinogen, antithrombin, protein C, and Tissue Factor Pathway Inhibitor decreased, and free protein S increased with tamoxifen but not with AIs. The observed shift toward increased coagulability associated with tamoxifen is in line with its known increased risk of VTE. In contrast, AIs do not appear to impact hemostasis, suggesting a lack of associated VTE risk. The trial was registered at www.clinicaltrials.gov as <a href="https://www.clinicaltrials.gov/ct2/show/NCT03381963" rel="noopener noreferrer" target="_blank">#NCT03381963</a>.
Keywords Aromatase Inhibitors / adverse effectsBreast Neoplasms / drug therapyFemaleHumansMaleProspective StudiesProtein CTamoxifen / adverse effectsThrombinVenous Thromboembolism / chemically inducedAromatase InhibitorsTamoxifen
PMID: 35086148
PMCID: PMC9092409
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Research groups Geneva Platelet Group (13)
La maladie thromboembolique veineuse (808)
Recherche translationnelle : anomalies de l'hémostase et thromboses (504)
(ISO format)
BLONDON, Marc et al. Differential impact of tamoxifen and aromatase inhibitors on thrombin generation: the prospective HEMOBREAST cohort. In: Blood advances, 2022, vol. 6, n° 9, p. 2884-2892. doi: 10.1182/bloodadvances.2021006623 https://archive-ouverte.unige.ch/unige:161681

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Deposited on : 2022-06-24

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