TGF-beta 1 levels in pre-treatment plasma identify breast cancer patients at risk of developing post-radiotherapy fibrosis

A serious complication of radiotherapy in the treatment of cancer patients is the late onset of fibrosis in normal tissues. Transforming growth factor 13 (TGF-beta) is emerging as a key mediator of the fibrotic process throug h its effects on stimulation of fibroblast proliferation, migration and ext racellular matrix (ECM) synthesis. The fact that radiation-induced vascular injury tends to precede the development of fibrosis has led to the suggest ion that vascular damage is crucial in its pathogenesis. CD105, the specifi c type III vascular receptor for TGF-beta 1 and -beta 3, modulates cell pro liferation and ECM production in response to TGF-beta in vitro. In this stu dy, we have quantified the levels of TGF-beta 1 and soluble CD105-TGF-beta 1 complex in 91 pre-radiotherapy plasma samples from early-stage (T1 or T2) breast cancer patients utilising an enhanced chemiluminescence ELISA syste m. During the follow-up period, 24 patients had developed moderate and one severe fibrosis of the breast. The mean TGF-beta 1 level in these 25 patien ts was 203.2 +/- 37.3 pg/ml, which was significantly elevated above the lev el for those with no fibrosis. Furthermore, a significantly lower CD105-TGF -beta 1 complex level was observed in the former compared to the latter. Sp earman's correlation analysis showed that TGF-beta 1 was positively correla ted and the CD105-TGF beta 1 complex inversely correlated with the occurren ce of breast fibrosis. Using a cut off value of 96 pg/ml, the sensitivity a nd specificity of TCF-beta 1 revels in predicting breast fibrosis were 76% and 74%, respectively. Our results indicate that TGF-beta 1 and the recepto r-ligand complex appear to be of clinical value in identifying patients at risk of developing post-radiotherapy fibrosis. Int. J. Cancer (Pred. Oncol. ) 84: 155-159, 1999. (C) 1999 Wiley-Liss, Inc.