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

Navita Somaiah, Melvin L.K. Chua, Sara Bourne, Frances Daley, Roger A'Hern, Otilia Nuta, Lone Gothard, Sue Boyle, Carsten Herskind, Ann Pearson, Jim Warrington, Sarah Helyer, Roger Owen, Kai Rothkamm, John Yarnold

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Aim To correlate residual double strand breaks (DSB) 24 h after 4 Gy 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 ≥5 years 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 24 h after a 4 Gy test dose in 20 RT-S and 15 RT-R patients. Residual DSB were quantified in lymphocytes irradiated with 4 Gy 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 4 Gy 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.

Original languageEnglish
Pages (from-to)244-249
Number of pages6
JournalRadiotherapy and Oncology
Volume119
Issue number2
DOIs
Publication statusPublished - May 1 2016

Keywords

  • Breast cancer
  • DNA damage response
  • Late adverse effects
  • Radiotherapy

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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