: 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  < 0.05, low vs. high risk). Conclusion  Our data validate the ETP parameter with a fully automated standardized system and confirm its significant contribution in identifying high-risk early breast cancer at risk for E-DR during chemotherapy.

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 / P. Gomez-Rosas, M. Pesenti, C. Verzeroli, C. Giaccherini, L. Russo, R. Sarmiento, G. Masci, L. Celio, M. Minelli, S. Gamba, C.J. Tartari, C. Tondini, F. Giuliani, F. Petrelli, A. D'Alessio, G. Gasparini, R. Labianca, A. Santoro, F. De Braud, M. Marchetti, A. Falanga. - In: TH OPEN. - ISSN 2512-9465. - 5:1(2021), pp. e56-e65. [10.1055/s-0040-1722609]

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

C. Giaccherini;L. Russo;S. Gamba;F. Petrelli;A. D'Alessio;F. De Braud;
2021

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  < 0.05, low vs. high risk). Conclusion  Our data validate the ETP parameter with a fully automated standardized system and confirm its significant contribution in identifying high-risk early breast cancer at risk for E-DR during chemotherapy.
breast cancer; disease recurrence; hypercoagulability; risk model; thrombin generation;
Settore MED/06 - Oncologia Medica
2021
10-feb-2021
Article (author)
File in questo prodotto:
File Dimensione Formato  
Validation of the role of trombine.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 394.29 kB
Formato Adobe PDF
394.29 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/908373
Citazioni
  • ???jsp.display-item.citation.pmc??? 4
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact