Relationship between residual radiation-induced DNA double-strand breaks in cultured fibroblasts and late radiation reactions: a comparison of training and validation cohorts of breast cancer patients.

Abstract

BACKGROUND AND PURPOSE: Using pulsed field gel electrophoresis (PFGE) a significant correlation was demonstrated between residual DNA double-strand breaks (dsbs) and the development of late radiation fibrosis in a group of 39 breast cancer patients studied retrospectively. This group formed a training cohort generating a hypothesis that there is a relationship between residual radiation-induced DNA dsbs in cultured fibroblasts and late radiotherapy reactions in breast cancer patients. The aim of this study was to retest and validate the hypothesis.MATERIALS AND METHODS: The study was retrospective. Skin biopsies were taken from a validation cohort of 50 breast cancer patients and PFGE was used to examine residual radiation-induced dsbs in cultured fibroblasts. Late morbidity was measured clinically as fibrosis and using the late effects on normal tissues scales that incorporate subjective, objective management and analytic data (LENT SOMA).RESULTS: PFGE data were obtained for 49 biopsies. In the 49 patients there was no correlation between residual DNA damage and either fibrosis (r=-0.027, P=0.85) or LENT SOMA (r=-0.10, P=0.48) scores. There was no significant relationship between residual damage and fibrosis for the combined training and validation cohorts of 88 patients (r=0.20, P=0.063).CONCLUSIONS: This study did not validate the hypothesis that there is a relationship between fibroblast residual DNA damage and late morbidity in breast cancer patients. The PFGE assay on fibroblasts is not a suitable test of the degree of late radiation-induced fibrosis in the breast.