Validation of the Role of Thrombin Generation Potential by a Fully Automated System in the Identification of Breast Cancer Patients at High Risk of Disease Recurrence

• Published in: TH open : companion journal to thrombosis and haemostasis 2021-01, Vol.5 (1), p.e56-e65
• Main Authors: Gomez-Rosas, Patricia, Pesenti, Marina, Verzeroli, Cristina, Giaccherini, Cinzia, Russo, Laura, Sarmiento, Roberta, Masci, Giovanna, Celio, Luigi, Minelli, Mauro, Gamba, Sara, Tartari, Carmen Julia, Tondini, Carlo, Giuliani, Francesco, Petrelli, Fausto, D'Alessio, Andrea, Gasparini, Giampietro, Labianca, Roberto, Santoro, Armando, De Braud, Filippo, Marchetti, Marina, Falanga, Anna
• Format: Article
• Language: English
• Subjects: breast cancer; disease recurrence; hypercoagulability; Original; Original Article; risk model; thrombin generation
• ISSN: 2512-9465; 2567-3459; 2512-9465
• DOI: 10.1055/s-0040-1722609

Abstract Background  The measurement of thrombin generation (TG) potential by the calibrated automated thrombogram (CAT) assay provides a strong contribution in identifying patients at high risk of early disease recurrence (E-DR). However, CAT assay still needs standardization and clinical validation. Objective  In this study, we aimed to validate the role of TG for E-DR prediction by means of the fully automated ST Genesia system. Methods  A prospective cohort of 522 patients from the HYPERCAN study with newly diagnosed resected high-risk breast cancer was included. Fifty-two healthy women acted as controls. Plasma samples were tested for protein C, free-protein S, and TG by ST Genesia by using the STG-ThromboScreen reagent with and without thrombomodulin (TM). Results  In the absence of TM, patients showed significantly higher peak and ETP compared with controls. In the presence of TM, significantly lower inhibition of ETP and Peak were observed in patients compared with controls. E-DR occurred in 28 patients; these patients had significantly higher peak and endogenous thrombin potential (ETP) in the absence of TM compared with disease-free patients. Multivariable analysis identified mastectomy, luminal B HER2-neg, triple negative subtypes, and ETP as independent risk factors for E-DR. These variables were combined to generate a risk assessment score, able to stratify patients in three-risk categories. The E-DR rates were 0, 4.7, and 13.5% in the low-, intermediate-, and high-risk categories (hazard ratio = 8.7; p