title: Functional impairment of activated protein C in breast cancer - relationship to survival outcomes.
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.
authors.affiliation: Department of Systems Medicine, Medical Oncology, Policlinico Tor Vergata Biospecimen Cancer Repository (PTV Bio.Ca.Re.), Tor Vergata University of Rome Viale Oxford 81, 00133 Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Roselli
authors.affiliation: San Raffaele Roma Open University Via di Val Cannuta 247, 00166 Rome, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.affiliation: Department of Systems Medicine, Medical Oncology, Policlinico Tor Vergata Biospecimen Cancer Repository (PTV Bio.Ca.Re.), Tor Vergata University of RomeViale Oxford 81, 00133 Rome, Italy; Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele PisanaVia di Val Cannuta 247, 00166 Rome, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Riondino
authors.affiliation: Department of Systems Medicine, Medical Oncology, Policlinico Tor Vergata Biospecimen Cancer Repository (PTV Bio.Ca.Re.), Tor Vergata University of Rome Viale Oxford 81, 00133 Rome, Italy.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Mariotti
authors.affiliation: Department of Systems Medicine, Medical Oncology, Policlinico Tor Vergata Biospecimen Cancer Repository (PTV Bio.Ca.Re.), Tor Vergata University of Rome Viale Oxford 81, 00133 Rome, Italy.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Portarena
authors.affiliation: Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele PisanaVia di Val Cannuta 247, 00166 Rome, Italy; Clinical Biochemistry and Molecular Biology, Department of Experimental Medicine and Surgery, Tor Vergata University of RomeItaly.
authors.forename: Jhessica
authors.initials: J
authors.lastname: Alessandroni
authors.affiliation: Clinical Biochemistry and Molecular Biology, Department of Experimental Medicine and Surgery, Tor Vergata University of Rome Italy.
authors.forename: Cristiano
authors.initials: C
authors.lastname: Ialongo
authors.affiliation: Clinical Biochemistry and Molecular Biology, Department of Experimental Medicine and Surgery, Tor Vergata University of Rome Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Massoud
authors.affiliation: Department of Pathology, San Giovanni Hospital-Addolorata Via dell'Amba Aradan 9, 00184 Rome, Italy.
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Costarelli
authors.affiliation: Department of Surgery, San Giovanni Hospital-Addolorata Via dell'Amba Aradan 9, 00184 Rome, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavaliere
authors.affiliation: Clinical Biochemistry and Molecular Biology, Department of Experimental Medicine and Surgery, Tor Vergata University of Rome Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Bernardini
authors.affiliation: San Raffaele Roma Open UniversityVia di Val Cannuta 247, 00166 Rome, Italy; Interinstitutional Multidisciplinary Biobank (BioBIM), IRCCS San Raffaele PisanaVia di Val Cannuta 247, 00166 Rome, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
keywords: Breast cancer; activated protein C resistance; disease-free survival; prognosis; thrombophilia