title: Survival and prognostic factors in BRCA1-associated breast cancer.
abstract: BACKGROUND
  Studies comparing survival in BRCA1-associated and sporadic breast cancer (BC) report inconsistent results and frequently concern small sample sizes. Further, the prognostic impact of the classical tumour and treatment factors is unclear in BRCA1-associated BC.
  
  
  METHODS
  We selected 223 BC patients diagnosed between 1980 and 2001 within families with a deleterious germline BRCA1-mutation ascertained at the Rotterdam Family Cancer Clinic. To correct for ascertainment bias, the group of index patients undergoing DNA testing more than 2 years after BC diagnosis (n = 53) was separated from the other BRCA1-patients (n = 170). All BRCA1-associated patients were matched in a 1:2 ratio for age and year of diagnosis to sporadic BC patients. We compared the occurrence of ipsi- and contralateral BC (CBC) as well as distant disease-free (DDFS), BC-specific (BCSS) and overall survival (OS). By multivariate modelling, the prognostic impact of tumour and treatment factors was investigated separately in BRCA1-associated and sporadic breast cancers.
  
  
  RESULTS
  For the total group of 669 cases, the median follow-up was 5.1 years, the median age at diagnosis 39 years. We confirmed the existence of the typical BRCA1-associated tumour type and the high CBC incidence. No significant differences between BRCA1-associated and sporadic tumours were found with respect to ipsilateral BC recurrence (HR(mult) 0.7; P = 0.24), DDFS (HR(mult) 1.2; P = 0.37) or BC-specific survival (HR(mult) 1.3; P = 0.23). A trend towards a worse survival was found for BRCA1-associated ductal BC (HR(mult) 1.5, P = 0.07). Prognostic factors for BRCA1-associated BC were age at diagnosis, tumour size and morphology, and nodal status. Further, survival was non-significantly improved by systemic treatment and a bilateral salpingo-oophorectomy. No effect on survival of a contralateral prophylactic mastectomy was seen.
  
  
  CONCLUSIONS
  BRCA1-associated BC is characterised by specific tumour characteristics, a high incidence of CBC and a trend towards a worse survival for the ductal tumour type. Our observation that tumour size and nodal status are also prognostic factors for BRCA1-associated BC implies that the strategy to use these factors as a proxy for ultimate mortality, for instance in BC screening programmes or the consideration of (contralateral) preventive mastectomy, appears to be valid in this specific group of patients.
authors.affiliation: Department of Medical Oncology, Department of Surgical Oncology and Department of Clinical Genetics, Family Cancer Clinic, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. c.brekelmans@erasmusmc.nl
authors.forename: C T M
authors.initials: CT
authors.lastname: Brekelmans
authors.forename: C
authors.initials: C
authors.lastname: Seynaeve
authors.forename: M
authors.initials: M
authors.lastname: Menke-Pluymers
authors.forename: H T
authors.initials: HT
authors.lastname: Brüggenwirth
authors.forename: M M A
authors.initials: MM
authors.lastname: Tilanus-Linthorst
authors.forename: C C M
authors.initials: CC
authors.lastname: Bartels
authors.forename: M
authors.initials: M
authors.lastname: Kriege
authors.forename: A N
authors.initials: AN
authors.lastname: van Geel
authors.forename: C M G
authors.initials: CM
authors.lastname: Crepin
authors.forename: J C
authors.initials: JC
authors.lastname: Blom
authors.forename: H
authors.initials: H
authors.lastname: Meijers-Heijboer
authors.forename: J G M
authors.initials: JG
authors.lastname: Klijn
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D006801:Humans; D011379:Prognosis; D016019:Survival Analysis