title: Worse breast cancer prognosis of BRCA1/BRCA2 mutation carriers: what's the evidence? A systematic review with meta-analysis.
abstract: OBJECTIVE
  Conflicting conclusions have been published regarding breast cancer survival of BRCA1/2 mutation carriers. Here we provide an evidence-based systematic literature review.
  
  
  METHODS
  Eligible publications were observational studies assessing the survival of breast cancer patients carrying a BRCA1/2 mutation compared to non-carriers or the general breast cancer population. We performed meta-analyses and best-evidence syntheses for survival outcomes taking into account study quality assessed by selection bias, misclassification bias and confounding.
  
  
  RESULTS
  Sixty-six relevant studies were identified. Moderate evidence for a worse unadjusted recurrence-free survival for BRCA1 mutation carriers was found. For BRCA1 and BRCA2 there was a tendency towards a worse breast cancer-specific and overall survival, however, results were heterogeneous and the evidence was judged to be indecisive. Surprisingly, only 8 studies considered adjuvant treatment as a confounder or effect modifier while only two studies took prophylactic surgery into account. Adjustment for tumour characteristics tended to shift the observed risk estimates towards a relatively more favourable survival.
  
  
  CONCLUSIONS
  In contrast to currently held beliefs of some oncologists, current evidence does not support worse breast cancer survival of BRCA1/2 mutation carriers in the adjuvant setting; differences if any are likely to be small. More well-designed studies are awaited.
authors: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors: Alexandra J
authors: AJ
authors: van den Broek
authors: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, Netherlands; Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors: Marjanka K
authors: MK
authors: Schmidt
authors: Division of Molecular Pathology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors: Laura J
authors: LJ
authors: van 't Veer
authors: Department of Surgery, Leiden University Medical Centre, Leiden, Netherlands.
authors: Rob A E M
authors: RA
authors: Tollenaar
authors: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute, Amsterdam, Netherlands.
authors: Flora E
authors: FE
authors: van Leeuwen
mesh_terms: D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D009154:Mutation / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human