title: Patients with double primary tumors in the breast and ovary- clinical characteristics and BRCA1-2 mutations status.
abstract: OBJECTIVE
  The aim of this study was to define the prevalence, clinical characteristics, and BRCA1-2 mutation carrier status of ovarian cancer (OvC) patients with a previous primary malignancy in the breast (PPMBr).
  
  
  METHODS
  The study population comprised 1240 consecutive Jewish Israeli women with pathologically confirmed epithelial OvC diagnosed between March 1, 1994, and December 31, 1997. Demographic and clinical data were obtained from medical files and from a detailed questionnaire taken through a nationwide epidemiological case-control study on OvC. Blood samples and tumor tissues were collected for analysis of the three predominant germline BRCA1-2 Jewish founder mutations (185delAG, 5382insC, and 6174delT).
  
  
  RESULTS
  Fifty nine (4.7%) patients with OvC had a PPMBr. The median age at diagnosis of OvC was 60 years. The mean interval between the two diagnoses was 104 months (range 0-363 months). In the majority of the patients (n = 53), the diagnosis of breast cancer (BrC) preceded the OvC by more than 1 year. The ovarian tumors were diagnosed in 47% of the cases following investigation of patients' symptoms. In 41%, diagnosis was made as a consequence of check-up exams performed during the routine follow-up of BrC survivors. Patients with PPMBr were more likely to present with FIGO ovarian stage III-IV, compared to women with solitary OvC (73% vs 60. 3%, P < 0.05), and less likely to have borderline tumors (3.4% vs 17. 9%, P = 0.007). Family history of OvC/BrC was recorded in 26% of this group of patients compared to 10.5% among patients with solitary OvC (P = 0.003). Patients with PPMBr had an exceptionally high prevalence of BRCA1-2 mutations (57%), irrespective of family history.
  
  
  CONCLUSIONS
  Patients with PPMBr present with more advanced disease and invasive-type epithelial ovarian tumors when compared to cases associated with solitary OvC. The rate of BRCA1-2 mutations in Jewish women with OvC who had PPMBr is at least twice as high as in Jewish women with OvC as the solitary disease.
authors.affiliation: Meir Hospital-Sapir Medical Center, Kfar-Saba, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Fishman
authors.forename: E
authors.initials: E
authors.lastname: Dekel
authors.forename: A
authors.initials: A
authors.lastname: Chetrit
authors.forename: L
authors.initials: L
authors.lastname: Lerner-Geva
authors.forename: A
authors.initials: A
authors.lastname: Bar-Am
authors.forename: D
authors.initials: D
authors.lastname: Beck
authors.forename: U
authors.initials: U
authors.lastname: Beller
authors.forename: G
authors.initials: G
authors.lastname: Ben-Baruch
authors.forename: B
authors.initials: B
authors.lastname: Piura
authors.forename: E
authors.initials: E
authors.lastname: Friedman
authors.forename: J P
authors.initials: JP
authors.lastname: Struewing
authors.forename: B
authors.initials: B
authors.lastname: Modan
mesh_terms: D024682:BRCA2 Protein; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D019398:Genes, BRCA1 / Q000235:genetics*; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D007557:Israel / Q000453:epidemiology; D007585:Jews / Q000235:genetics*; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D015995:Prevalence; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D024682:BRCA2 Protein; D009363:Neoplasm Proteins; D014157:Transcription Factors