Transforming Growth Factor β-1 (TGF-β1) Is a Serum Biomarker of Radiation Induced Fibrosis in Patients Treated With Intracavitary Accelerated Partial Breast Irradiation: Preliminary Results of a Prospective Study

Purpose: To examine a relationship between serum transforming growth factor beta-1 (TGF-beta 1) values and radiation-induced fibrosis (RIF). Methods and Materials: We conducted a prospective analysis of the development of RIF in 39 women with American Joint Committee on Cancer stage 0-I breast cancer treated with lumpectomy and accelerated partial breast irradiation via intracavitary brachytherapy (IBAPBI). An enzyme-linked immunoassay (Quantikine, R&D, Minneapolis, MN) was used to measure serum TGF-beta 1 before surgery, before IBAPBI, and during IBAPBI. Blood samples for TGF-beta 1 were also collected from 15 healthy, nontreated women (controls). The previously validated tissue compliance meter (TCM) was used to objectively assess RIF. Results: The median time to follow-up for 39 patients was 44 months (range, 5-59 months). RIF was graded by the TCM scale as 0, 1, 2, and 3 in 5 of 20 patients (25%), 6 of 20 patients (30%), 5 of 20 patients (25%), and 4 of 20 patients (20%), respectively. The mean serum TGF-beta 1 values were significantly higher in patients before surgery than in disease-free controls, as follows: all cancer patients (30,201 +/- 5889 pg/mL, P=.02); patients with any type of RIF (32,273 +/- 5016 pg/mL, P<.0001); and women with moderate to severe RIF (34,462 +/- 4713 pg/mL, P<0.0001). Patients with moderate to severe RIF had significantly elevated TGF-beta 1 levels when compared with those with none to mild RIF before surgery (P=.0014) during IBAPBI (P <= 0001), and the elevation persisted at 6 months (P <=.001), 12 months (P <=.001), 18 months (P <=.001), and 24 months (P=.12). A receiver operating characteristic (ROC) curve of TGF-beta 1 values predicting moderate to severe RIF was generated with an area under the curve (AUC)(ROC) of 0.867 (95% confidence interval 0.700-1.000). The TGF-beta 1 threshold cutoff was determined to be 31,000 pg/mL, with associated sensitivity and specificity of 77.8% and 90.0%, respectively. Conclusions: TGF-beta 1 levels correlate with the development of moderate to severe RIF. The pre-IBAPBI mean TGF-beta 1 levels can serve as an early biomarker for the development of moderate to severe RIF after IBAPBI. (C) 2013 Elsevier Inc.