TY - JOUR
T1 - Thrombotic biomarkers for risk prediction of malignant disease recurrence in patients with early stage breast cancer
AU - Giaccherini, Cinzia
AU - Marchetti, Marina
AU - Masci, Giovanna
AU - Verzeroli, Cristina
AU - Russo, Laura
AU - Celio, Luigi
AU - Sarmiento, Roberta
AU - Gamba, Sara
AU - Tartari, Carmen J
AU - Diani, Erika
AU - Vignoli, Alfonso
AU - Malighetti, Paolo
AU - Spinelli, Daniele
AU - Tondini, Carlo
AU - Barni, Sandro
AU - Giuliani, Francesco
AU - Petrelli, Fausto
AU - D'Alessio, Andrea
AU - Gasparini, Giampietro
AU - De Braud, Filippo
AU - Santoro, Armando
AU - Labianca, Roberto
AU - Falanga, Anna
N1 - Copyright © 2019, Ferrata Storti Foundation.
PY - 2019/9/26
Y1 - 2019/9/26
N2 - In cancer patients, hypercoagulability is a common finding and it has been associated to an increased risk of venous thromboembolisms, but also to tumor proliferation and progression. In this prospective study, in a large cohort of patients with breast cancer, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: 1. are associated with breast cancer-specific clinicopathological features; and 2. 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 prothrombin fragment 1+2 levels were significantly associated with tumor size and lymph node metastasis. After 3.4 years follow-up, 71 patients experienced a recurrence. Cox-multivariate analysis identified prothrombin fragment 1+2, tumor size, and Luminal B HER2-neg or triple negative molecular subtypes as independent risk factors for disease recurrence. Based on these variables, we generated a risk assessment model that significantly differentiated patients at low- and high-risk of recurrence (cumulative incidence: 6.2 vs 20.7%; HR=3.5; p<0.001). Our prospective clinical and laboratory data from the HYPERCAN study were crucial for generating a scoring model for disease recurrence risk assessment in resected breast cancer patients, candidate to systemic chemotherapy. This finding stimulates future investigations addressing the role of plasma prothrombin fragment 1+2 in breast cancer patients' management, and in providing the rationale for new therapeutic strategies.
AB - In cancer patients, hypercoagulability is a common finding and it has been associated to an increased risk of venous thromboembolisms, but also to tumor proliferation and progression. In this prospective study, in a large cohort of patients with breast cancer, we aimed to evaluate whether pre-chemotherapy abnormalities in hemostatic biomarkers levels: 1. are associated with breast cancer-specific clinicopathological features; and 2. 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 prothrombin fragment 1+2 levels were significantly associated with tumor size and lymph node metastasis. After 3.4 years follow-up, 71 patients experienced a recurrence. Cox-multivariate analysis identified prothrombin fragment 1+2, tumor size, and Luminal B HER2-neg or triple negative molecular subtypes as independent risk factors for disease recurrence. Based on these variables, we generated a risk assessment model that significantly differentiated patients at low- and high-risk of recurrence (cumulative incidence: 6.2 vs 20.7%; HR=3.5; p<0.001). Our prospective clinical and laboratory data from the HYPERCAN study were crucial for generating a scoring model for disease recurrence risk assessment in resected breast cancer patients, candidate to systemic chemotherapy. This finding stimulates future investigations addressing the role of plasma prothrombin fragment 1+2 in breast cancer patients' management, and in providing the rationale for new therapeutic strategies.
U2 - 10.3324/haematol.2019.228981
DO - 10.3324/haematol.2019.228981
M3 - Article
C2 - 31558668
JO - Haematologica
JF - Haematologica
SN - 0390-6078
ER -