Correlation between DNA damage responses of skin to a test dose of radiation and late adverse effects of earlier breast radiotherapy

Abstract Aim 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 and methods 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. Results 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). Conclusions 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.