title: Risk of metachronous breast cancer after BRCA mutation-associated ovarian cancer.
abstract: BACKGROUND
  This study sought to estimate the risk of breast cancer (BC) after a diagnosis of ovarian cancer (OC) associated with mutation of the BRCA1/2 (breast cancer, early onset) genes (BRCA-OC).
  
  
  METHODS
  The Memorial Sloan-Kettering Cancer Center and the University of Pennsylvania, clinical genetics databases were searched to identify women with BRCA-OC who participated in genetic testing and follow-up studies from 1995 to 2009. The primary objective was to determine the risk of developing BC after BRCA-OC. Overall survival (OS) and BC-free survival (BCFS) were determined by the Kaplan-Meier method; patients were censored at the time of last follow-up.
  
  
  RESULTS
  A total of 164 patients had BRCA-OC (115 with BRCA1; 49 with BRCA2). Of these 164 patients, 152 developed OC prior to BRCA testing (median time to testing, 2.4 years [0.01-55 years]). Median follow-up from OC for those not developing BC was 5.8 years (0.25-55.6 years). There were 46 deaths, but none were due to BC. The 5- and 10-year OS were 85% (95% confidence interval [CI] = 0.78, 0.90) and 68% (95% CI = 0.59, 0.76), respectively. There were 18 metachronous BC diagnoses. The 5- and 10-year BCFS were 97% (95% CI = 0.92, 0.99) and 91% (95% CI = 0.82, 0.95), respectively. A subset of 64 women were tested either before or within 12 months of BRCA-OC. In this pseudo-incident subset, 5- and 10- year OS was 71% (95% CI = 0.53, 0.83) and 62% (95% CI = 0.44, 0.75), respectively, and 5- and 10-year BCFS were 100% and 87% (95% CI = 0.56, 0.96), respectively.
  
  
  CONCLUSIONS
  OS was dominated by OC deaths. Metachronous BC risk was lower than reported for unaffected BRCA mutation carriers. These results support nonsurgical management of BC risk in women with BRCA-OC.
authors.affiliation: University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Domchek
authors.forename: Komal
authors.initials: K
authors.lastname: Jhaveri
authors.forename: Sujata
authors.initials: S
authors.lastname: Patil
authors.forename: Jill E
authors.initials: JE
authors.lastname: Stopfer
authors.forename: Clifford
authors.initials: C
authors.lastname: Hudis
authors.forename: Jacquelyn
authors.initials: J
authors.lastname: Powers
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Stadler
authors.forename: Laura
authors.initials: L
authors.lastname: Goldstein
authors.forename: Noah
authors.initials: N
authors.lastname: Kauff
authors.forename: Mustafa
authors.initials: M
authors.lastname: Khasraw
authors.forename: Kenneth
authors.initials: K
authors.lastname: Offit
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Nathanson
authors.forename: Mark
authors.initials: M
authors.lastname: Robson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics*; D012306:Risk; D013997:Time Factors; D055815:Young Adult