Screening of Circulating TGF-β Levels and Its Clinicopathological Significance in Human Breast Cancer

Background: Transforming growth factor beta-1 (TGF-β1) participation in breast cancer development and metastasis is well-established, however, the clinical meaning of its circulating levels in women with breast cancer is poorly understood. Aim: To characterize the levels of TGF- β1 in plasma from women with breast cancer and to associate them with the main clinical factors associated with disease prognosis. Patients and Methods: TGF-β1 levels were measured by Enzyme-linked immunoassay (ELISA). Clinicopathological data were also assessed. Results: Women bearing triple-negative tumors presented significantly reduced levels of this cytokine when compared to the other subtypes (p=0.0338). Patients with metastases exhibited lower levels of TGF-β1 than the non-metastatic cohort (p=0.0442). Patients with early-onset disease had the highest plasma TGF-β1 levels (p=0.0036). Doxorubicin chemotherapy induced a reduction in TGF-β1 level, promptly after drug infusion (p=0.0494). Patients with TGF-β1 levels lower than 20 pg/ml exhibited a tendency to have a reduced overall survival in a 40-month follow-up. Conclusion: Lower levels of circulating TGF-β1 are associated with a poor disease prognosis. Transforming growth factor beta (TGF-β) is a family of growth factors that affect both normal and neoplastic processes in the mammary gland. This pleiotropic cytokine is well-implicated in regulating tissue remodeling and apoptosis in normal breast development (1). The role of TGF-β1, the most abundant isoform of TGF-β, in normal breast is based on its tumor suppressor functions. However, in breast cancer, this cytokine has tumor-promoting functions, especially in cells that evade TGF-β1-regulating properties during metastatic progression (2). Effects of TGF-β1 can be systemically observed beyond the tumor microenvironment, since virtually all cells present with TGF-β receptors (1). TGF-β also displays a redox- sensor function, as evidenced during experimental radiation response (3). It has been implicated in several processes, mediated by reactive species, particularly inflammation, aiming at the restoration of homeostasis. This redox-sensor activity seems to further regulate the reactive oxygen species (ROS) production in chronic processes (3).