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


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.
Russell
N S
NS
Department of Radiotherapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoekhuis, Amsterdam. nrus@nki.nl
Lara
P C
PC
Grummels
A
A
Hart
A A
AA
Coco-Martin
J M
JM
Bartelink
H
H
Begg
A C
AC
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000473:pathology / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D002454:Cell Differentiation; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000528:radiation effects; D005355:Fibrosis; D006801:Humans; D008875:Middle Aged; D011878:Radiotherapy / Q000009:adverse effects*