TGF-β1 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 β (TGF-β) is emerging as a key mediator of the fibrotic process through its effects on stimulation of fibroblast proliferation, migration and extracellular matrix (ECM) synthesis. The fact that radiation-induced vascular injury tends to precede the development of fibrosis has led to the suggestion that vascular damage is crucial in its pathogenesis. CD105, the specific type III vascular receptor for TGF-β1 and -β3, modulates cell proliferation and ECM production in response to TGF-β in vitro. In this study, we have quantified the levels of TGF-β1 and soluble CD105–TGF-β1 complex in 91 pre-radiotherapy plasma samples from early-stage (T1 or T2) breast cancer patients utilising an enhanced chemiluminescence ELISA system. During the follow-up period, 24 patients had developed moderate and one severe fibrosis of the breast. The mean TGF-β1 level in these 25 patients was 203.2 ± 37.3 pg/ml, which was significantly elevated above the level for those with no fibrosis. Furthermore, a significantly lower CD105–TGF-β1 complex level was observed in the former compared to the latter. Spearman's correlation analysis showed that TGF-β1 was positively correlated and the CD105–TGFβ1 complex inversely correlated with the occurrence of breast fibrosis. Using a cut-off value of 96 pg/ml, the sensitivity and specificity of TGF-β1 levels in predicting breast fibrosis were 76% and 74%, respectively. Our results indicate that TGF-β1 and the receptor–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. © 1999 Wiley-Liss, Inc.