Evaluation of predictive biomarkers for late radiation toxicity in breast cancer patients

Radiotherapy is administered to 70% of breast cancer patients, but late complications such as breast fibrosis remain a significant clinical concern. Individual variability significantly influences radiosensitivity, underscoring the need for predictive biomarkers suitable for clinical application. We evaluated five assays using blood samples from 22 matched pairs of treated breast cancer patients, including one female who developed fibrosis grade II or higher and a female who did not. Matching was performed accounting for treatment type, tumor characteristics, and other variables. The assays included γ-H2AX detection, radiation-induced apoptosis evaluation, and cytogenetic analysis by chromosomal instability testing, and assessment of radiation-induced damage in G0- and G2- phase lymphocytes. The results indicated that patients who developed fibrosis presented significantly lower values in the G2 assay and higher values in the chromosomal instability test. The G2 assay evaluates the integrity of the G2/M checkpoint, while the chromosomal instability test measures chromosomal instability through crosslink sensitivity. In contrast, the other evaluated tests did not discriminate between groups. Considering the cohort and the variability in all tests, our results suggest that G2 assay and chromosomal instability test would be robust predictors of radiotherapy-induced breast fibrosis. Validation in a larger retrospective or prospective study is necessary.