title: Breast Cancer Survival of BRCA1/BRCA2 Mutation Carriers in a Hospital-Based Cohort of Young Women.
abstract: The primary aim of the study was to investigate prognosis and long-term survival in young breast cancer patients with a BRCA1 or BRCA2 germline mutation compared with noncarriers. The secondary aim was to investigate whether differences in survival originate from associations with tumor characteristics, second cancers, and/or treatment response.
  
  
  
  We established a cohort of invasive breast cancer patients diagnosed younger than age 50 years in 10 Dutch hospitals between 1970 and 2003. BRCA1/2 testing of most prevalent mutations was mainly done using DNA isolate from formalin-fixed paraffin-embedded nontumor tissue. Survival estimates were derived using Cox regression and competing risk models.
  
  
  
  In 6478 breast cancer patients, we identified 3.2% BRCA1 and 1.2% BRCA2 mutation carriers. BRCA1 mutation carriers had a worse overall survival independent of clinico-pathological/treatment characteristics, compared with noncarriers (adjusted hazard ratio [HR] = 1.20, 95% confidence interval [CI] = 0.97 to 1.47), though only statistically significant in the first five years of follow-up (adjusted HR = 1.40, 95% CI = 1.07 to 1.84). A large part of the worse survival was explained by incidence of ovarian cancers. Breast cancer-specific, disease-free, and metastasis-free survival results were less pronounced and mostly statistically nonsignificant but in the same direction with those of overall survival. Overall survival was worse, although not statistically significantly, within the ER-negative or ER-positive, grade 3, and small tumor subgroups. The worse survival was most pronounced in non-chemotherapy-treated patients (adjusted HR = 1.54, 95% CI = 1.08 to 2.19). Power for BRCA2 mutation carriers was limited; only after five years' follow-up overall survival was worse (adjusted HR = 1.47, 95% CI = 1.00 to 2.17).
  
  
  
  BRCA1/2 mutation carriers diagnosed with breast cancer before age 50 years are prone to a worse survival, which is partly explained by differences in tumor characteristics, treatment response, and second ovarian cancers.
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.|Division of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.
authors.forename: Marjanka K
authors.initials: MK
authors.lastname: Schmidt
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.|Division of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.
authors.forename: Alexandra J
authors.initials: AJ
authors.lastname: van den Broek
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Rob A E M
authors.initials: RA
authors.lastname: Tollenaar
authors.affiliation: Department of Pathology,  Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Vincent T H B M
authors.initials: VT
authors.lastname: Smit
authors.affiliation: Laboratory for Pathology, Dordrecht, The Netherlands.
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Westenend
authors.affiliation: Laboratory for Pathology East-Netherlands, Hengelo, The Netherlands.
authors.forename: Mariël
authors.initials: M
authors.lastname: Brinkhuis
authors.affiliation: Department of Pathology (Josephine Nefkens Institute), Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Wolter J W
authors.initials: WJ
authors.lastname: Oosterhuis
authors.affiliation: Division of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.|Department of Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.
authors.forename: Jelle
authors.initials: J
authors.lastname: Wesseling
authors.affiliation: Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands.|Department of Clinical Epidemiology, VieCuri Medical Centre, Venlo, The Netherlands.
authors.forename: Maryska L
authors.initials: ML
authors.lastname: Janssen-Heijnen
authors.affiliation: Department of Radiotherapy, Medisch Spectrum Twente, Enschede, The Netherlands.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Jobsen
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Agnes
authors.initials: A
authors.lastname: Jager
authors.affiliation: Department of Research, Netherlands Comprehensive Cancer Organization, Utrecht, The Netherlands.|Department of Epidemiology, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: Adri C
authors.initials: AC
authors.lastname: Voogd
authors.affiliation: Division of Psychosocial Research and Epidemiology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.
authors.forename: Flora E
authors.initials: FE
authors.lastname: van Leeuwen
authors.affiliation: Division of Molecular Pathology, Netherlands Cancer Institute-Antoni van Leeuwenhoek Amsterdam, The Netherlands.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: van 't Veer
mesh_terms: D000328:Adult; D000367:Age Factors; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D018270:Carcinoma, Ductal, Breast / Q000235:genetics* / Q000401:mortality* / Q000556:secondary / Q000628:therapy; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D018095:Germ-Line Mutation; D006579:Heterozygote; D006761:Hospitals; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D009426:Netherlands / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D000072036:Prophylactic Mastectomy; D015996:Survival Rate
chemical_list: D000970:Antineoplastic Agents