Circulating soluble Fas concentration in breast cancer patients

Fas/Fas ligand (FasL) system, a major regulator of apoptosis, is involved in cancer cell death induced by the immune system and anticancer drugs. Fas is a cell-surface receptor that exists in two forms, transmembrane and soluble. The former induces apoptosis by ligation of FasL or agonistic anti-Fas antibody, whereas the latter inhibits Fas-mediated apoptosis by neutralizing its ligand. In this study, we examined circulating soluble Fas (sFas) concentration in 118 healthy people, 162 primary and 71 recurrent breast cancer patients by ELISA. In the healthy group, men showed higher sFas concentrations than women (P<0.001). In both sexes, sFas levels increased with age, and the age-matched cutoff value was determined. The median sFas concentration in primary and recurrent cancer patients was 0.815 and 1.510 ng/ml, both of which were higher than in normal female controls (0.580 ng/ml; P = 0.024 and P<0.001, respectively). Among primary cancer patients, although no significant correlation was found between sFas concentration and clinical parameters other than menopausal status, high-sFas patients had a worse prognosis than low-sFas patients for both overall and disease-free survival (P = 0.013 and P = 0.032, respectively). The multivariate analysis confirmed that circulating sFas concentration was an independent prognostic indicator (P = 0.020 for overall survival, P = 0.025 for disease-free survival). We looked at the recurrent cancer patients, and sFas levels were higher in patients with liver metastasis compared with those with other recurrent sites (P = 0.010), and high-sFas patients showed a worse prognosis than low-sFas patients (P = 0.037). Our data demonstrate that, compared with healthy female controls, breast cancer patients, especially those with liver metastases, have higher circulating sFas levels. sFas may be useful once these results are confirmed by larger studies.