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CC BY 4.0 · TH Open 2021; 05(01): e56-e65
DOI: 10.1055/s-0040-1722609
Original Article

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

Patricia Gomez-Rosas 
1   Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
2   Hematology Service, Hospital General Regional Tecamac, IMSS, Estado de Mexico, Mexico
,
Marina Pesenti
1   Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Cristina Verzeroli
1   Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Cinzia Giaccherini
1   Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Laura Russo
1   Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Roberta Sarmiento
3   Oncology Unit, Hospitals San Filippo Neri and San Giovanni Addolorata, Rome, Italy
,
Giovanna Masci
4   Medical Oncology and Hematology, IRCCS Humanitas Institute, Rozzano, Italy
,
Luigi Celio
5   Medical Oncology and Hematology, IRCCS National Cancer Institute, Milan, Italy
,
Mauro Minelli
3   Oncology Unit, Hospitals San Filippo Neri and San Giovanni Addolorata, Rome, Italy
,
Sara Gamba
1   Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Carmen Julia Tartari
1   Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Carlo Tondini
6   Oncology Unit, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Francesco Giuliani
7   Medical Oncology Unit, IRCCS Istituto Tumori Giovanni Paolo II, Bari, Italy
,
Fausto Petrelli
8   Oncology Unit, Hospital Treviglio-Caravaggio, Treviglio, Italy
,
Andrea D'Alessio
9   Department of Medicine, Gruppo San Donato, Policlinico San Marco, Bergamo, Italy
,
Giampietro Gasparini
3   Oncology Unit, Hospitals San Filippo Neri and San Giovanni Addolorata, Rome, Italy
,
Roberto Labianca
10   Department of Oncology Bergamo Province, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Armando Santoro
4   Medical Oncology and Hematology, IRCCS Humanitas Institute, Rozzano, Italy
,
Filippo De Braud
5   Medical Oncology and Hematology, IRCCS National Cancer Institute, Milan, Italy
,
Marina Marchetti‡   ∗
1   Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
,
Anna Falanga   ∗
1   Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo, Italy
11   School of Medicine, University of Milan Bicocca, Italy
,
on behalf of the HYPERCAN Investigators › Author Affiliations Funding This study received support from Associazione Italiana per la Ricerca sul Cancro (AIRC 5xmille 12237) and Fondazione ARTET Onlus.
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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.

Keywords

breast cancer - disease recurrence - hypercoagulability - risk model - thrombin generation

# A full list of the investigators of the HYPERCAN (HYPERcoagulation in CANcer) Study Group is provided in [Supplementary Material]. HYPERCAN is registered at www.clinicaltrials.gov under the identifier: NCT02622815.


∗ These authors contributed equally as the co-last authors.


Supplementary Material



Publication History

Received: 23 September 2020

Accepted: 07 December 2020

Article published online:
10 February 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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