title: Risk of asynchronous contralateral breast cancer in noncarriers of BRCA1 and BRCA2 mutations with a family history of breast cancer: a report from the Women's Environmental Cancer and Radiation Epidemiology Study.
abstract: OBJECTIVE
  To fully characterize the risk of contralateral breast cancer (CBC) in patients with breast cancer with a family history who test negative for BRCA1 and BRCA2 mutations.
  
  
  METHODS
  From our population-based case-control study comparing women with CBC to women with unilateral breast cancer (UBC), we selected women who tested negative for BRCA1 and BRCA2 mutations (594 patients with CBC/1,119 control patients with UBC). Rate ratios (RRs) and 95% CIs were estimated to examine the association between family history of breast cancer and risk of asynchronous CBC. Age- and family history-specific 10-year cumulative absolute risks of CBC were estimated.
  
  
  RESULTS
  Family history of breast cancer was associated with increased CBC risk; risk was highest among young women (< 45 years) with first-degree relatives affected at young ages (< 45 years; RR, 2.5; 95% CI, 1.1 to 5.3) or women with first-degree relatives with bilateral disease (RR, 3.6; 95% CI, 2.0 to 6.4). Women diagnosed with UBC before age 55 years with a first-degree family history of CBC had a 10-year risk of CBC of 15.6%.
  
  
  CONCLUSIONS
  Young women with breast cancer who have a family history of breast cancer and who test negative for deleterious mutations in BRCA1 and BRCA2 are at significantly greater risk of CBC than other breast cancer survivors. This risk varies with diagnosis age, family history of CBC, and degree of relationship to an affected relative. Women with a first-degree family history of bilateral disease have risks of CBC similar to mutation carriers. This has important implications for the clinical management of patients with breast cancer with family history of the disease.
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. reinera@mskcc.org
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.forename: Esther M
authors.initials: EM
authors.lastname: John
authors.forename: Jennifer D
authors.initials: JD
authors.lastname: Brooks
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Lene
authors.initials: L
authors.lastname: Mellemkjær
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
authors.forename: Julia A
authors.initials: JA
authors.lastname: Knight
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: Sharon N
authors.initials: SN
authors.lastname: Teraoka
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Liang
authors.forename: Jane C
authors.initials: JC
authors.lastname: Figueiredo
authors.forename: Susan A
authors.initials: SA
authors.lastname: Smith
authors.forename: Marilyn
authors.initials: M
authors.lastname: Stovall
authors.forename: Malcolm C
authors.initials: MC
authors.lastname: Pike
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.forename: Colin B
authors.initials: CB
authors.lastname: Begg
authors.forename: Jonine L
authors.initials: JL
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000453:epidemiology*; D016017:Odds Ratio; D017584:Reproductive History; D018570:Risk Assessment; D012307:Risk Factors; D014481:United States / Q000453:epidemiology
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human