title: Effect of radiotherapy after breast-conserving treatment in women with breast cancer and germline BRCA1/2 mutations.
abstract: OBJECTIVE
  Recent laboratory data suggest a role for BRCA1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA1/2 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease.
  
  
  METHODS
  Seventy-one women with a BRCA1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used to compare matched cohorts for rates of complications and recurrence.
  
  
  RESULTS
  Tumors from women in the genetic cohort were associated with high histologic (P =.0004) and nuclear (P =.009) grade and negative estrogen (P=.0001) and progesterone (P=.002) receptors compared with tumors from the sporadic cohort. Using Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity scoring, there were no significant differences in acute or chronic morbidity in skin, subcutaneous tissue, lung, or bone. The 5-year actuarial overall survival, relapse-free survival, and rates of tumor control in the treated breast for the patients in the genetic cohort were 86%, 78%, and 98%, respectively, compared with 91%, 80%, and 96%, respectively, for the sporadic cohort (P = not significant).
  
  
  CONCLUSIONS
  There was no evidence of increased radiation sensitivity or sequelae in breast tissue heterozygous for a BRCA1/2 germline mutation compared with controls, and rates of tumor control in the breast and survival were comparable between BRCA1/2 carriers and controls at 5 years. Although additional follow-up is needed, these data may help in discussing treatment options in the management of early-stage hereditary breast cancer and should provide reassurance regarding the safety of administering RT to carriers of a germline BRCA1/2 mutation.
authors.affiliation: Department of Radiation Oncology, University of Michigan, and University of Michigan Cancer Center Biostatistics Core, Ann Arbor, MI, USA. ljpierce@umich.edu
authors.forename: L J
authors.initials: LJ
authors.lastname: Pierce
authors.forename: M
authors.initials: M
authors.lastname: Strawderman
authors.forename: S A
authors.initials: SA
authors.lastname: Narod
authors.forename: I
authors.initials: I
authors.lastname: Oliviotto
authors.forename: A
authors.initials: A
authors.lastname: Eisen
authors.forename: L
authors.initials: L
authors.lastname: Dawson
authors.forename: D
authors.initials: D
authors.lastname: Gaffney
authors.forename: L J
authors.initials: LJ
authors.lastname: Solin
authors.forename: A
authors.initials: A
authors.lastname: Nixon
authors.forename: J
authors.initials: J
authors.lastname: Garber
authors.forename: C
authors.initials: C
authors.lastname: Berg
authors.forename: C
authors.initials: C
authors.lastname: Isaacs
authors.forename: R
authors.initials: R
authors.lastname: Heimann
authors.forename: O I
authors.initials: OI
authors.lastname: Olopade
authors.forename: B
authors.initials: B
authors.lastname: Haffty
authors.forename: B L
authors.initials: BL
authors.lastname: Weber
mesh_terms: D000328:Adult; D000368:Aged; D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000235:genetics* / Q000532:radiotherapy* / Q000601:surgery; D015331:Cohort Studies; D004249:DNA Damage / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D016609:Neoplasms, Second Primary / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics; D011832:Radiation Injuries / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects; D012189:Retrospective Studies; D016019:Survival Analysis; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors