Grossberg AJ, et al. - Researchers evaluated the link between the C-509T variant allele in the promoter region of TGFB1 and breast fibrosis 3 years following radiotherapy. This investigation seems to be the first prospective validation of a genomic marker for radiation fibrosis. They found that breast fibrosis risk was essentially determined by the C-509T allele in TGFB1. To enable a more tailored approach to locoregional treatment decisions in breast cancer, evaluating TGFB1 genotype may be helpful.

Methods

• Researchers performed this a priori–specified, prospective, cohort study nested in an open-label, randomized clinical trial, conducted in community-based and academic cancer centers to compare hypofractionated whole-breast irradiation (WBI) (42.56 Gy in 16 fractions) with conventionally fractionated WBI (50 Gy in 25 fractions) after breast-conserving surgery.
• From February 2011 to February 2014, enrollment of 287 women 40 years or older with pathologically confirmed stage 0 to IIA breast cancer treated with breast-conserving surgery was carried out.
• For a minimum of 3 years, patients were under observation.
• The 1-sided Fisher exact test and multivariable logistic regression were used to compare outcomes.
• Exposures included a C-to-T single-nucleotide polymorphism at position -509 relative to the first major transcription start site (C-509T) of the TGFB1 gene.
• As the primary outcome, grade 2 or higher breast fibrosis was assessed using the Late Effects Normal Tissue/Subjective, Objective, Medical Management, Analytic scale (range 0 to 3) 3 years after radiotherapy.

Results

• This trial included 287 women, with 174 patients who had available TGFB1 genotype and 3-year radiotherapy-induced toxicity data, of whom 89 patients (51%) with a mean (SD) age of 60 (8) years had at least 1 copy of C-509T.
• Findings revealed the presence of grade 2 or higher breast fibrosis in 12 of 87 patients with C-509T (13.8%), vs 3 of 80 patients without the allele variant (3.8%) (absolute difference, 10.0%; 95% CI, 1.7%-18.4%; P=.02).
• In multivariable analyses, only C-509T (odds ratio, 4.47; 95% CI, 1.25-15.99; P=.02) and postoperative cosmetic outcome (odds ratio, 7.09; 95% CI, 2.41-20.90; P < .001) were found to be significantly related to breast fibrosis risk.