TGFB1 gene key determinant of breast fibrosis risk
medwireNews: Carriers of the C−509T allele in the transforming growth factor ß 1 (TGFB1) gene have a significantly increased risk for late breast fibrosis following breast-conserving surgery and whole-breast irradiation for stage 0 to IIA breast cancer, researchers report.
“The association of C−509T with fibrosis occurred independent of the radiotherapy fractionation regimen or postsurgical, preradiotherapy cosmesis, the only other factor associated with breast fibrosis,” write Benjamin Smith (The University of Texas MD Anderson Cancer Center, Houston, USA) and colleagues in JAMA Oncology.
Just over half (51%) of the 174 women (mean age 60 years) included in the study had at least one copy of the C−509T polymorphism in the TGFB1 gene, and its distribution varied by race/ethnicity: 48% of 130 non-Hispanic White women were carriers, compared with 75% of 24 Hispanic White women and 35% of 17 Black women.
At 3 years post whole-breast irradiation with either a hypofractionated (42.56 Gy in 16 fractions) or conventionally fractionated (50 Gy in 25 fractions) regimen, the rate of breast fibrosis was significantly higher among the women who carried the C−509T allele versus those who did not.
Specifically, 13.8% of women with the C−509T allele had grade 2 or higher fibrosis, as assessed using the Late Effects Normal Tissue/Subjective, Objective, Medical Management, Analytic scale (range, 0 to 3), compared with 3.8% of those without the T allele.
On multivariate analysis, carrying the C−509T allele was associated with a significant 4.5-fold increased likelihood for grade 2 or higher fibrosis at 3 years. The only other significant predictor of this degree of fibrosis was having a fair or poor postoperative, preradiotherapy cosmetic outcome, at an odds ratio of 7.1.
Of note, neither physicians nor patients reported a significant difference in cosmesis at 3 years between C−509T carriers and non-carriers suggesting that “adverse cosmetic outcome is a multifactorial process attributable not simply to susceptibility to radiation fibrosis but also to disease, host, and surgical factors,” Smith et al remark.
The researchers believe their study is the first to prospectively validate “a genomic factor associated with late radiation fibrosis, substantiating a role for somatic genomic toxicity stratification in a clinical oncology population.”
They suggest that “[a]ssessing TGFB1 genotype may facilitate a more personalized approach to locoregional treatment decisions in breast cancer.”
The authors conclude: “Further investigations on the role of TGFB1 genotyping in lymphedema risk assessment and breast reconstruction decisions are ongoing.”
By Laura Cowen
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