title: [Bilateral breast carcinoma and local recurrence: prevalence of BRCA-1 and BRCA-2 gene mutations in an unselected patient sample].
abstract: BACKGROUND
  Mutations of the BRCA 1/BRCA 2 genes strongly predispose towards the development of contralateral breast cancer. We therefore investigated a hospital-based series of patients with bilateral breast cancer and a comparison group of patients with unilateral breast cancer, pairwise matched by age and family history, for mutations of the BRCA 1/BRCA 2 genes.
  
  
  METHODS
  Between 1995 and 2000 genomic DNA from blood samples of 75 patients with bilateral breast cancer, who received postoperative radiotherapy, was analyzed for mutations of all coding regions and flanking intron sequences of the BRCA 1/BRCA 2 genes by single strand conformation polymorphism analysis (SSCP) and sequencing of aberrant findings. The results were compared to 75 unilateral breast cancer patients who were screened for common mutations in the BRCA 1 and BRCA 2 genes. Treatment results of patients with bilateral disease were analyzed with regard to a possible carriership of a BRCA 1/BRCA 2 gene mutation.
  
  
  RESULTS
  Five distinct frameshift deletions (one in BRCA 1, four in BRCA 2) were identified in six patients with bilateral breast cancer. Three of six carriers developed local relapse, whereas this was the case in only nine of 69 non-carriers. After radiotherapy local relapse occurred in five patients (five of 126 irradiated breasts or chest walls). Three of these patients (60%) were carriers of a pathogenic BRCA 1/BRCA 2 mutation. In the comparison group of patients with unilateral breast cancer three pathogenic BRCA 1 mutations were identified.
  
  
  CONCLUSIONS
  We failed to confirm an increased prevalence of BRCA 1/BRCA 2 mutations in our hospital-based series of patients with bilateral breast cancer. However, local relapse, especially when occurring after radiotherapy, may be predictive for an underlying pathogenic BRCA 1 and BRCA 2 gene mutation in patients with bilateral breast cancer.
authors.affiliation: Abteilung für Strahlentherapie und Spezielle Onkologie, Medizinische Hochschule Hannover. bremer.michael@mh-hannover.de
authors.forename: M
authors.initials: M
authors.lastname: Bremer
authors.forename: D
authors.initials: D
authors.lastname: Steinmann
authors.forename: T
authors.initials: T
authors.lastname: Dörk
authors.forename: J
authors.initials: J
authors.lastname: Börger
authors.forename: D
authors.initials: D
authors.lastname: Rades
authors.forename: J H
authors.initials: JH
authors.lastname: Karstens
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein; D001940:Breast / Q000473:pathology; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D002872:Chromosome Deletion; D003131:Combined Modality Therapy; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D006580:Genetic Carrier Screening; D006801:Humans; D016555:Matched-Pair Analysis; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000235:genetics* / Q000473:pathology / Q000532:radiotherapy; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors
vernacular_title: Bilaterales Mammakarzinom und Lokalrezidiv: Prävalenz von BRCA-1- und BRCA-2-Genmutationen an einem unselektionierten Kollektiv.