In vitro differentiation characteristics of human skin fibroblasts: correlations with radiotherapy-induced breast fibrosis in patients

Abstract

Purpose : To determine whether there is an association between dermal fibroblast differentiation characteristics in vitro and breast fibrosis developing in patients following radiotherapy for breast cancer. Materials and methods : Three hundred and eighty-five patients had been characterized for the degree of breast fibrosis and the level of clinical risk factors for fibrosis as established by logistic regression. Early-passage fibroblasts from 79 patients with a high (HR) or low (LR) level of risk factors were studied in vitro. The percentage differentiated cells (%DC) 7 days after 0 and 8 Gy was scored, and unirradiated colonies were scored for the ratio of early:late fibroblast differentiation stages (E:L ratio). Results : %DC: For the 0 Gy data there was a significant interpatient variation (CoV=55%, p=0.0001). HR patients with breast fibrosis had a higher %DC compared with patients without (p =0.017). E:L ratio: for HR patients there was a significant interpatient variation (82%, p =0.0030) and a lower E:L ratio for patients with fibrosis compared with those without (p =0.086), but for LR patients this relationship was reversed (p =0.079) Conclusions : There was a true interpatient variation in the in vitro parameters of fibroblast differentiation but insufficient correlation with observed fibrosis after radiotherapy for use as a predictive test.