Correlation between DNA damage responses of skin to a test dose of radiation and late adverse effects of earlier breast radiotherapy.
To correlate residual double strand breaks (DSB) 24h after 4Gy test doses to skin in vivo and to lymphocytes in vitro with adverse effects of earlier breast radiotherapy (RT).



Patients given whole breast RT ⩾5years earlier were identified on the basis of moderate/marked or minimal/no adverse effects despite the absence ('RT-Sensitive', RT-S) or presence ('RT-Resistant', RT-R) of variables predisposing to late adverse effects. Residual DSB were quantified in skin 24h after a 4Gy test dose in 20 RT-S and 15 RT-R patients. Residual DSB were quantified in lymphocytes irradiated with 4Gy in vitro in 30/35 patients.



Mean foci per dermal fibroblast were 3.29 (RT-S) vs 2.80 (RT-R) (p=0.137); 3.28 (RT-S) vs 2.60 (RT-R) in endothelium (p=0.158); 2.50 (RT-S) vs 2.41 (RT-R) in suprabasal keratinocytes (p=0.633); 2.70 (RT-S) vs 2.35 (RT-R) in basal epidermis (p=0.419); 12.1 (RT-S) vs 10.3 (RT-R) in lymphocytes (p=0.0052).



Residual DSB in skin following a 4Gy dose were not significantly associated with risk of late adverse effects of breast radiotherapy, although exploratory analyses suggested an association in severely affected individuals. By contrast, a significant association was detected based on the in vitro response of lymphocytes.
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK. Electronic address: navita.somaiah@icr.ac.uk.
Navita
N
Somaiah
Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, UK; Division of Radiation Oncology, National Cancer Centre, Singapore, Duke-NUS Graduate Medical School, Singapore.
Melvin L K
ML
Chua
CRUK/MRC Oxford Institute for Radiation Oncology, University of Oxford, UK.
Sara
S
Bourne
Division of Breast Cancer Research, The Institute of Cancer Research, London, UK.
Frances
F
Daley
ICR-CTSU, Division of Clinical Studies, The Institute of Cancer Research, London, UK.
Roger
R
A' Hern
Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, UK.
Otilia
O
Nuta
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.
Lone
L
Gothard
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.
Sue
S
Boyle
Department of Radiation Oncology, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Germany.
Carsten
C
Herskind
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.
Ann
A
Pearson
Physics Department, The Royal Marsden NHS Foundation Trust, London, UK.
Jim
J
Warrington
Radiotherapy Department, The Royal Marsden NHS Foundation Trust, London, UK.
Sarah
S
Helyer
Gloucestershire Oncology Centre, Cheltenham General Hospital, UK.
Roger
R
Owen
Public Health England, Centre for Radiation, Chemical and Environmental Hazards, Chilton, UK; Department of Radiotherapy and Radiation Oncology, University Medical Center Hamburg-Eppendorf, Germany.
Kai
K
Rothkamm
Division of Radiotherapy and Imaging, The Institute of Cancer Research, London, UK.
John
J
Yarnold
D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000528:radiation effects*; D001943:Breast Neoplasms / Q000532:radiotherapy*; D053903:DNA Breaks, Double-Stranded; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects; D008875:Middle Aged; D011879:Radiotherapy Dosage; D012867:Skin / Q000378:metabolism / Q000528:radiation effects*
Breast cancer; DNA damage response; Late adverse effects; Radiotherapy