title: Individual radiosensitivity measured with lymphocytes may be used to predict the risk of fibrosis after radiotherapy for breast cancer.
abstract: OBJECTIVE
  To analyse the relationship of individual cellular radiosensitivity and fibrosis after breast conserving therapy. A new model was used describing the percentage of patients developing fibrosis per year and per patient at risk.
  
  
  METHODS
  In a retrospective study, 86 patients were included, who had undergone breast conserving surgery and irradiation of the breast with a median dose of 55 Gy (54-55 Gy) given at 2.5 Gy/fraction (n=57) or 2 Gy/fraction (n=29). Median age was 62 years (range 44-86) and median follow-up was 7.5 years (range 5-17). Patients were examined for fibrosis according to the LENT/SOMA score. For analysis, fibrosis was classified as grade 0 and grade 1 (G0-1) or present grade 2 and grade 3 (G2-3). The time to complete development of fibrosis was determined by analysis of yearly mammograms. Individual cellular radiosensitivity was determined by scoring lethal chromosomal aberrations in in vitro irradiated (6 Gy) lymphocytes using metaphase technique. Patients with low/intermediate cellular radiosensitivity were compared with patients with high cellular radiosensitivity using actuarial methods.
  
  
  RESULTS
  Ten patients developed fibrosis at 1-8 years after radiotherapy. Individual cellular radiosensitivity was described by normal distribution of lethal chromosomal aberrations, the average was 5.47 lethal aberrations per cell (standard deviation (SD) 0.71). Cellular radiosensitivity was defined as low/intermediate (< or =6.18 lethal aberrations) in 73 patients and high (>6.18 lethal aberrations; mean+SD) in 13 patients. In both groups, the actuarial rate of fibrosis-free patients decreased exponentially with time after radiotherapy. Patients with high cellular radiosensitivity showed a 2.3-fold higher annual rate for fibrosis than patients with intermediate and low radiosensitivity (3.6 versus 1.6% per year).
  
  
  CONCLUSIONS
  In breast cancer patients, high individual cellular radiosensitivity as determined by the number of lethal chromosome aberrations in in vitro irradiated lymphocytes might be associated with an enhanced annual rate of fibrosis.
authors.affiliation: Department of Radiotherapy and Radiooncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hoeller
authors.forename: Kerstin
authors.initials: K
authors.lastname: Borgmann
authors.forename: Michael
authors.initials: M
authors.lastname: Bonacker
authors.forename: Antje
authors.initials: A
authors.lastname: Kuhlmey
authors.forename: Amira
authors.initials: A
authors.lastname: Bajrovic
authors.forename: Horst
authors.initials: H
authors.lastname: Jung
authors.forename: Winfried
authors.initials: W
authors.lastname: Alberti
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Dikomey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics / Q000532:radiotherapy* / Q000601:surgery; D002869:Chromosome Aberrations; D005260:Female; D005355:Fibrosis / Q000209:etiology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology / Q000528:radiation effects*; D008875:Middle Aged; D011836:Radiation Tolerance / Q000235:genetics* / Q000276:immunology; D012189:Retrospective Studies