Functional impairment of activated protein C in breast cancer - relationship to survival outcomes

Mario Roselli, Patrizia Ferroni, Silvia Riondino, Sabrina Mariotti, Ilaria Portarena, Jhessica Alessandroni, Cristiano Ialongo, Renato Massoud, Leopoldo Costarelli, Francesco Cavaliere, Sergio Bernardini, Fiorella Guadagni

Research output: Contribution to journalArticlepeer-review

Abstract

An impairment of the activated protein C (APC) system has been occasionally reported in breast cancer (BC). However, the clinical significance and prognostic value of an impaired APC functionality in BC patients is still poorly understood. Thus, the present study was aimed at investigating the prognostic value of altered APC functionality for progression-free (PFS) and overall survival (OS) in a cohort study of BC patients. APC functionality was retrospectively analyzed by a coagulation inhibition assay (ThromboPath) in 290 consecutive patients with primary (n=246) or relapsing/recurrent (n=44) BC. All patients were prospectively followed for a median time of 3.5 years (14% recurrence rate). As control group, 145 age-matched healthy women were also investigated. The results obtained demonstrated that APC function was impaired in roughly 20% of all BC at baseline. BC women with stage I/II had a significantly lower rate of APC impairment (13%) than women with stage III (22%) or distant metastases (44%, p=0.001). At univariate analyses, an impairment of APC function had a negative prognostic impact in terms of PFS (5-year PFS rates 53% vs. 70%; HR=2.5; p<0.001) and OS (5-year OS rates 79% vs. 93%; HR=3.9; p=0.005). However, prognostic significance was retained in multivariate models only for PFS (HR=2.0; p=0.017). We may, thus, conclude that BC patients are in a prothrombotic condition, which could play a role in the progression of the disease. Monitoring coagulation changes in BC women could provide important prognostic information especially in patients with advanced stages.

Original languageEnglish
Pages (from-to)1450-1457
Number of pages8
JournalAmerican Journal of Cancer Research
Volume6
Issue number6
Publication statusPublished - 2016

Keywords

  • Activated protein C resistance
  • Breast cancer
  • Disease-free survival
  • Prognosis
  • Thrombophilia

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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