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

Purpose: To determine whether there is an association between dermal fibrob last differentiation characteristics in vitro and breast fibrosis developin g in patients following radiotherapy for breast cancer. Materials and methods: Three hundred and eighty-five patients had been char acterized for the degree of breast fibrosis and the level of clinical risk factors for fibrosis as established by logistic regression. Early-passage f ibroblasts from 79 patients with a high (HR) or low (LR) level of risk fact ors were studied in vitro. The percentage differentiated cells (%DC) 7 days after 0 and 8Gy 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 varia tion (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 t here 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 parame ters of fibroblast differentiation but insufficient correlation with observ ed fibrosis after radiotherapy for use as a predictive test.