Prognostic utility of circulating transforming growth factor beta 1 in breast cancer patients

Abstract

Transforming growth factor betas (TGF-βs) are multifunctional cytokines with a biphasic role in breast tumorigenesis, acting as tumor suppressors at early stages while stimulating tumor progression at later stages (TGF-β switch). Among the 3 human isoforms, TGF-β1 is known to be overexpressed in several tumor types including breast tumors. TGF-β signaling and “crosstalk” in the tumor microenvironment presents a unique challenge and an opportunity to develop novel therapies. We assessed circulating TGF-β1 levels by ELISA in blood samples from 117 previously untreated breast cancer patients in this prospective study to explore the TGF-β switch at the forefront. The levels were correlated with clinicopathological prognosticators like age, menopausal status, nodal status, histological type, histological grade, necrosis, stromal involvement, and survival. Higher mean preoperative serum TGF-β1 was observed in early-stage patients than controls (p=0.05) as revealed by receiver operating characteristic (ROC) analysis. Elevation of TGF-β1 was evident in patients with advanced-stage breast cancer compared with those having early-stage disease (p=0.0001). Prognosticators of an aggressive phenotype were associated with higher TGF-β1 levels, and higher levels thus announced the likelihood of relapse, marking the role of TGF-β1 as a tumor promoter and evidencing the existence of a TGF-β switch. Moreover, higher levels of TGF-β1 shortened the overall survival in breast cancer patients (p=0.010). The results indicate that circulating TGF-β1 may be used as a predictive and prognostic marker in breast carcinoma.