title: Factors modifying the risk for developing acute skin toxicity after whole-breast intensity modulated radiotherapy.
abstract: BACKGROUND
  After breast-conserving radiation therapy most patients experience acute skin toxicity to some degree. This may impair patients' quality of life, cause pain and discomfort. In this study, we investigated treatment and patient-related factors, including genetic polymorphisms, that can modify the risk for severe radiation-induced skin toxicity in breast cancer patients.
  
  
  METHODS
  We studied 377 patients treated at Ghent University Hospital and at ST.-Elisabeth Clinic and Maternity in Namur, with adjuvant intensity modulated radiotherapy (IMRT) after breast-conserving surgery for breast cancer. Women were treated in a prone or supine position with normofractionated (25 × 2 Gy) or hypofractionated (15 × 2.67 Gy) IMRT alone or in combination with other adjuvant therapies. Patient- and treatment-related factors and genetic markers in regulatory regions of radioresponsive genes and in LIG3, MLH1 and XRCC3 genes were considered as variables. Acute dermatitis was scored using the CTCAEv3.0 scoring system. Desquamation was scored separately on a 3-point scale (0-none, 1-dry, 2-moist).
  
  
  RESULTS
  Two-hundred and twenty patients (58%) developed G2+ dermatitis whereas moist desquamation occurred in 56 patients (15%). Normofractionation (both p < 0.001), high body mass index (BMI) (p = 0.003 and p < 0.001), bra cup size ≥ D (p = 0.001 and p = 0.043) and concurrent hormone therapy (p = 0.001 and p = 0.037) were significantly associated with occurrence of acute dermatitis and moist desquamation, respectively. Additional factors associated with an increased risk of acute dermatitis were the genetic variation in MLH1 rs1800734 (p=0.008), smoking during RT (p = 0.010) and supine IMRT (p = 0.004). Patients receiving trastuzumab showed decreased risk of acute dermatitis (p < 0.001).
  
  
  CONCLUSIONS
  The normofractionation schedule, supine IMRT, concomitant hormone treatment and patient related factors (high BMI, large breast, smoking during treatment and the genetic variation in MLH1 rs1800734) were associated with increased acute skin toxicity in patients receiving radiation therapy after breast-conserving surgery. Trastuzumab seemed to be protective.
authors.forename: Sofie
authors.initials: S
authors.lastname: De Langhe
authors.forename: Thomas
authors.initials: T
authors.lastname: Mulliez
authors.forename: Liv
authors.initials: L
authors.lastname: Veldeman
authors.forename: Vincent
authors.initials: V
authors.lastname: Remouchamps
authors.forename: Annick
authors.initials: A
authors.lastname: van Greveling
authors.forename: Monique
authors.initials: M
authors.lastname: Gilsoul
authors.forename: Eline
authors.initials: E
authors.lastname: De Schepper
authors.forename: Kim
authors.initials: K
authors.lastname: De Ruyck
authors.forename: Wilfried
authors.initials: W
authors.lastname: De Neve
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Proeftuinstraat 86, 9000 Ghent, Belgium. Hubert.Thierens@UGent.be.
authors.forename: Hubert
authors.initials: H
authors.lastname: Thierens
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018931:Antineoplastic Agents, Hormonal / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000235:genetics* / Q000601:surgery / Q000628:therapy*; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011855:Radiodermatitis / Q000453:epidemiology*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018931:Antineoplastic Agents, Hormonal; C501486:MLH1 protein, human; D009687:Nuclear Proteins; D000070957:MutL Protein Homolog 1