title: 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.
abstract: OBJECTIVE
  To examine a relationship between serum transforming growth factor β -1 (TGF-β1) values and radiation-induced fibrosis (RIF).
  
  
  METHODS
  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-β1 before surgery, before IBAPBI, and during IBAPBI. Blood samples for TGF-β1 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-β1 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-β1 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-β1 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-β1 threshold cutoff was determined to be 31,000 pg/mL, with associated sensitivity and specificity of 77.8% and 90.0%, respectively.
  
  
  CONCLUSIONS
  TGF-β1 levels correlate with the development of moderate to severe RIF. The pre-IBAPBI mean TGF-β1 levels can serve as an early biomarker for the development of moderate to severe RIF after IBAPBI.
authors.affiliation: Weill Cornell Medical College of Cornell University, New York, New York.
authors.forename: Dustin L
authors.initials: DL
authors.lastname: Boothe
authors.forename: Shana
authors.initials: S
authors.lastname: Coplowitz
authors.forename: Eleni
authors.initials: E
authors.lastname: Greenwood
authors.forename: Christian L
authors.initials: CL
authors.lastname: Barney
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Christos
authors.forename: Bhupesh
authors.initials: B
authors.lastname: Parashar
authors.forename: Dattatreyudu
authors.initials: D
authors.lastname: Nori
authors.forename: K S Clifford
authors.initials: KS
authors.lastname: Chao
authors.forename: A Gabriella
authors.initials: AG
authors.lastname: Wernicke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods; D001940:Breast / Q000473:pathology / Q000528:radiation effects; D001943:Breast Neoplasms / Q000097:blood / Q000532:radiotherapy* / Q000601:surgery; D016022:Case-Control Studies; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D057234:Preoperative Period; D011446:Prospective Studies; D012372:ROC Curve; D011832:Radiation Injuries / Q000097:blood* / Q000473:pathology; D017564:Radiation Pneumonitis; D012016:Reference Values; D012680:Sensitivity and Specificity; D012867:Skin / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D015415:Biomarkers; D053773:Transforming Growth Factor beta1