title: Increased incidence of visceral metastases in scottish patients with BRCA1/2-defective ovarian cancer: an extension of the ovarian BRCAness phenotype.
abstract: OBJECTIVE
  To compare the frequency of visceral relapse of BRCA1/2-deficient ovarian cancer to that of nonhereditary controls.
  
  
  METHODS
  All patients diagnosed in Scotland with epithelial ovarian cancer (EOC) or primary peritoneal cancer (PPC) and a germline BRCA1/2 mutation were identified. Those with previous malignancy were excluded. Each remaining patient who experienced relapse was matched with two nonhereditary controls.
  
  
  RESULTS
  Seventy-nine patients with EOC/PPC and germline BRCA1/2 mutations were identified. Fifteen had inadequate clinical data, two had carcinosarcoma, 27 had previous breast cancer, and 16 were in remission. Of the remaining 19 patients who were BRCA1/2 deficient, 14 patients (74%) developed visceral metastases compared with six (16%) of 38 patients in the control group. The percentages of liver, lung, and splenic metastases were 53%, 32%, and 32%, respectively, in the patients compared with 5%, 3%, and 5%, respectively, in the controls. When events occurring outside the matched follow-up period were omitted, the percentages of visceral, liver, lung, and splenic metastases were 58%, 42%, 16%, and 32% in the patients compared with 5%, 0%, 0%, and 3% in controls (P < .001, P < .001, P = .066, and P = .011, respectively). In an independent validation set, the corresponding percentages of visceral, liver, lung, and splenic metastases were 63%, 46%, 13%, and 17% in the patients compared with 11%, 4%, 2%, and 2% in controls (P < .001, P < .001, P = .153, and P = .052, respectively).
  
  
  CONCLUSIONS
  Although sporadic EOC commonly remains confined to the peritoneum, BRCA1/2-deficient ovarian cancer frequently metastasizes to viscera. These data extend the ovarian BRCAness phenotype, imply BRCA1/2-deficient ovarian cancer is biologically distinct, and suggest that patients with visceral metastases should be considered for BRCA1/2 sequencing.
authors.affiliation: University of Edinburgh Cancer Research Centre, Institute of Genetics and Molecular Medicine, Western General Hospital, Edinburgh, UK. charlie.gourley@ed.ac.uk
authors.forename: Charlie
authors.initials: C
authors.lastname: Gourley
authors.forename: Caroline O
authors.initials: CO
authors.lastname: Michie
authors.forename: Patricia
authors.initials: P
authors.lastname: Roxburgh
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Yap
authors.forename: Sharon
authors.initials: S
authors.lastname: Harden
authors.forename: Jim
authors.initials: J
authors.lastname: Paul
authors.forename: Kalpana
authors.initials: K
authors.lastname: Ragupathy
authors.forename: Radha
authors.initials: R
authors.lastname: Todd
authors.forename: Russell
authors.initials: R
authors.lastname: Petty
authors.forename: Nick
authors.initials: N
authors.lastname: Reed
authors.forename: Richard L
authors.initials: RL
authors.lastname: Hayward
authors.forename: Paul
authors.initials: P
authors.lastname: Mitchell
authors.forename: Tzyvia
authors.initials: T
authors.lastname: Rye
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
authors.forename: Jan
authors.initials: J
authors.lastname: Lubinski
authors.forename: James
authors.initials: J
authors.lastname: Carmichael
authors.forename: Stan B
authors.initials: SB
authors.lastname: Kaye
authors.forename: Melanie
authors.initials: M
authors.lastname: Mackean
authors.forename: Michelle
authors.initials: M
authors.lastname: Ferguson
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000235:genetics / Q000556:secondary; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D015994:Incidence; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D008875:Middle Aged; D009362:Neoplasm Metastasis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000556:secondary; D010641:Phenotype; D012606:Scotland; D013160:Splenic Neoplasms / Q000235:genetics / Q000556:secondary