Thrombin generation predicts early recurrence in breast cancer patients.

HYPERCAN Investigators, Marina Marchetti, Cinzia Giaccherini, Giovanna Masci, Cristina Verzeroli, Laura Russo, Luigi Celio, Roberta Sarmiento, Sara Gamba, Carmen J Tartari, Erika Diani, Alfonso Vignoli, Paolo Malighetti, Daniele Spinelli, Nicole M Kuderer, Federico Nichetti, Mauro Minelli, Carlo Tondini, Sandro Barni, Francesco GiulianiFausto Petrelli, Andrea D'Alessio, Giampietro Gasparini, Roberto Labianca, Armando Santoro, Filippo De Braud, Anna Falanga

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)2220-2231
Number of pages12
JournalJournal of Thrombosis and Haemostasis
Volume18
Issue number9
DOIs
Publication statusPublished - Sep 2020

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