Page 246 - Haematologica - Vol. 105 n. 6 - June 2020

Coagulation & its Disorders
Ferrata Storti Foundation
Haematologica 2020 Volume 105(6):1704-1711
Thrombotic biomarkers for risk prediction of malignant disease recurrence in patients with early stage breast cancer
Cinzia Giaccherini,1# Marina Marchetti,1# Giovanna Masci,2 Cristina Verzeroli,1 Laura Russo,1 Luigi Celio,3 Roberta Sarmiento,4 Sara Gamba,1 Carmen J. Tartari,1 Erika Diani,1 Alfonso Vignoli,1 Paolo Malighetti,5 Daniele Spinelli,5 Carlo Tondini,6 Sandro Barni,7 Francesco Giuliani,8 Fausto Petrelli,7 Andrea D’Alessio,9 Giampietro Gasparini,4 Filippo De Braud,3 Armando Santoro,2 Roberto Labianca10 and Anna Falanga,1,11 on behalf of the HYPERCAN Investigators**
1Immunohematology and Transfusion Medicine, Hospital Papa Giovanni XXIII, Bergamo; 2Oncology Unit, IRCCS Humanitas Institute, Rozzano; 3Oncology Unit, IRCCS National Cancer Institute, Milan; 4Oncology Unit, Hospital San Filippo Neri, Rome; 5Department of Management, Information and Production Engineering, University of Bergamo, Bergamo; 6Oncology Unit, Hospital Papa Giovanni XXIII, Bergamo; 7Oncology Unit, Hospital Treviglio-Caravaggio, Treviglio; 8Oncology Unit, IRCCS Cancer Institute Giovanni Paolo II, Bari; 9Medical Oncology and Internal Medicine, Policlinico San Marco, Zingonia- Bergamo; 10Department Oncology Bergamo Province, Hospital Papa Giovanni XXIII, Bergamo and 11University of Milan Bicocca, School of Medicine and Surgery, Milan, Italy
#CG and MM contributed equally as co-first authors.
**A full list of the Investigators of the HYPERCAN (HYPERcoagulation in CANcer) Study Group appears in the Appendix 1.
ABSTRACT
In cancer patients, hypercoagulability is a common finding. It has been associated with an increased risk of venous thromboembolism, but also to tumor proliferation and progression. In this prospective study of a large cohort of breast cancer patients, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: (i) are associated with breast cancer-specific clinico-pathological features; and (ii) can predict for disease recurrence. D-dimer, fibrinogen, prothrombin fragment 1+2, and FVIIa/antithrombin levels were measured in 701 early-stage resected breast cancer patients candidate to adjuvant chemotherapy and prospectively enrolled in the HYPERCAN study. Significant prognostic parameters for disease recurrence were identified by Cox regression multivariate analysis and used for generating a risk assessment model. Pre-chemotherapy D-dimer, fibrinogen, and pro- thrombin fragment 1+2 levels were significantly associated with tumor size and lymph node metastasis. After 3.4 years of follow up, 71 patients experienced a recurrence. Cox multivariate analysis identified prothrom- bin fragment 1+2, tumor size, and Luminal B HER2-negative or triple negative molecular subtypes as independent risk factors for disease recur- rence. Based on these variables, we generated a risk assessment model that significantly differentiated patients at low- and high-risk of recur- rence (cumulative incidence: 6.2 vs. 20.7%; Hazard Ratio=3.5; P<0.001). Our prospective clinical and laboratory data from the HYPERCAN study were crucial for generating a scoring model for assessing risk of disease recurrence in resected breast cancer patients, candidate to systemic chemotherapy. This finding stimulates future investigations addressing the role of plasma prothrombin fragment 1+2 in the management of breast cancer patients to provide the rationale for new therapeutic strate- gies. (The HYPERCAN study is registered at clinicaltrials.gov identifier 02622815.)
Correspondence:
ANNA FALANGA
annafalanga@yahoo.com
Received: June 7, 2019.
Accepted: September 24, 2019. Pre-published: September 26, 2019.
doi:10.3324/haematol.2019.228981
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/6/1704
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