title: Clinical outcomes in women with breast cancer and a PALB2 mutation: a prospective cohort analysis.
abstract: BACKGROUND
  Mutations in PALB2 predispose to breast cancer, but the effect on prognosis of carrying a PALB2 mutation has not been ascertained. We aimed to estimate the odds ratio for breast cancer in women with an inherited mutation in PALB2 and 10-year survival after breast cancer in patients who carry a PALB2 mutation.
  
  
  METHODS
  Between 1996 and 2012, patients with invasive breast cancer were recruited prospectively from 18 hospitals in Poland and genotyped for two deleterious mutations in PALB2 (509_510delGA and 172_175delTTGT). A control group of 4702 women without cancer was recruited for comparison. The primary endpoint was death from any cause, as determined by medical records from the Polish Ministry of the Interior and Administration. In patients with breast cancer, 10-year survival of carriers of a PALB2 mutation was calculated and compared with that of non-carriers.
  
  
  RESULTS
  17 900 women with breast cancer were invited to participate, of whom 12 529 were genotyped successfully. A PALB2 mutation was present in 116 (0·93%, 95% CI 0·76-1·09) of 12 529 patients and in ten (0·21%, 0·08-0·34) of 4702 controls (odds ratio 4·39, 95% CI 2·30-8·37; p<0·0001). 10-year survival for women with breast cancer and a PALB2 mutation was 48·0% (95% CI 36·5-63·2), compared with 74·7% (73·5-75·8) for patients with breast cancer without a mutation (adjusted hazard ratio for death 2·27, 95% CI 1·64-3·15; p<0·0001).
  
  
  CONCLUSIONS
  Women with a PALB2 mutation face an increased risk of breast cancer and might be at a higher risk of death from breast cancer compared with non-carriers. Increased surveillance should be offered to unaffected women who carry a PALB2 mutation.
  
  
  BACKGROUND
  Polish National Science Centre.
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Cezary
authors.initials: C
authors.lastname: Cybulski
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Kluźniak
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Huzarski
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Dominika
authors.initials: D
authors.lastname: Wokołorczyk
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Aniruddh
authors.initials: A
authors.lastname: Kashyap
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Jakubowska
authors.affiliation: Regional Oncology Center, Opole, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Szwiec
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Byrski
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Dębniak
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Bohdan
authors.initials: B
authors.lastname: Górski
authors.affiliation: Women's College Research Institute, Toronto, ON, Canada.
authors.forename: Victoria
authors.initials: V
authors.lastname: Sopik
authors.affiliation: Women's College Research Institute, Toronto, ON, Canada.
authors.forename: Mohammad R
authors.initials: MR
authors.lastname: Akbari
authors.affiliation: Women's College Research Institute, Toronto, ON, Canada.
authors.forename: Ping
authors.initials: P
authors.lastname: Sun
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Gronwald
authors.affiliation: Women's College Research Institute, Toronto, ON, Canada. Electronic address: steven.narod@wchospital.ca.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.affiliation: International Hereditary Cancer Center, Department of Genetics and Pathology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Jan
authors.initials: J
authors.lastname: Lubiński
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000076164:Fanconi Anemia Complementation Group N Protein; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000076164:Fanconi Anemia Complementation Group N Protein; D009687:Nuclear Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D025521:Tumor Suppressor Proteins; C512790:PALB2 protein, human; C508053:ERBB2 protein, human