Thrombin generation predicts early recurrence in breast cancer patients

• Published in: Journal of thrombosis and haemostasis Vol. 18; no. 9; pp. 2220 - 2231
• Main Authors: Marchetti, Marina, Giaccherini, Cinzia, Masci, Giovanna, Verzeroli, Cristina, Russo, Laura, Celio, Luigi, Sarmiento, Roberta, Gamba, Sara, Tartari, Carmen J., Diani, Erika, Vignoli, Alfonso, Malighetti, Paolo, Spinelli, Daniele, Kuderer, Nicole M., Nichetti, Federico, Minelli, Mauro, Tondini, Carlo, Barni, Sandro, Giuliani, Francesco, Petrelli, Fausto, D’Alessio, Andrea, Gasparini, Giampietro, Labianca, Roberto, Santoro, Armando, De Braud, Filippo, Falanga, Anna, Schieppati, Francesca, Martinetti, Antonia, Gennaro, Elisabetta, Ghilardi, Mara
• Format: Journal Article
• Language: English
• Published: England Elsevier Limited 01.09.2020
• Subjects: Breast cancer; Breast Neoplasms; Chemotherapy; disease recurrence; ErbB-2 protein; Humans; hypercoagulability; Mastectomy; Multivariate analysis; Neoplasm Recurrence, Local; Prognosis; Prospective Studies; Risk assessment; risk model; Surgery; Thrombin; thrombin generation; breast cancer; hypercoagulability; thrombin generation; disease recurrence; risk model
• ISSN: 1538-7933; 1538-7836; 1538-7836
• DOI: 10.1111/jth.14891

Background Cancer patients present with a hypercoagulable state often associated with poor disease prognosis. Objectives This study aims to evaluate whether thrombin generation (TG), a global coagulation test, may be a useful tool to improve the identification of patients at high risk of early disease recurrence (ie, E‐DR within 2 years) after breast cancer surgery. Patients/Methods A cohort of 522 newly diagnosed patients with surgically resected high‐risk breast cancer were enrolled in the ongoing prospective HYPERCAN study. TG potential was measured in plasma samples collected before starting systemic chemotherapy. Significant predictive hemostatic and clinic‐pathological parameters were identified in the derivation cohort by Cox regression analysis. A risk prognostic score for E‐DR was generated in the derivation and tested in the validation cohort. Results After a median observation period of 3.4 years, DR occurred in 51 patients, 28 of whom were E‐DR. E‐DR subjects presented with the highest TG values as compared to both late‐DR (from 2 to 5 years) and no relapse subjects (P < .01). Multivariate analysis in the derivation cohort identified TG, mastectomy, triple negative and Luminal B HER2‐neg molecular subtypes as significant independent predictors for E‐DR, which were utilized to generate a risk assessment score. In the derivation and validation cohorts, E‐DR rates were 2.3% and 0% in the low‐risk, 10.1% and 6.3% in the intermediate‐risk, and 18.2% and 16.7%, in the high‐risk categories, respectively. Conclusions Inclusion of TG in a risk‐assessment model for E‐DR significantly helps the identification of operated breast cancer patients at high risk of very early relapse.