title: Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2.
abstract: OBJECTIVE
  Women with breast cancer diagnosed early in life comprise a substantial portion of those tested for BRCA1/BRCA2 mutations; however, little information is available on the subsequent risks of contralateral breast cancer in mutation carriers. This study assessed the risk of subsequent contralateral breast cancer associated with carrying a BRCA1 or BRCA2 mutation.
  
  
  METHODS
  In this nested case-control study, patients with contralateral breast cancer diagnosed 1 year or more after a first primary breast cancer (n = 705) and controls with unilateral breast cancer (n = 1,398) were ascertained from an underlying population-based cohort of 52,536 women diagnosed with a first invasive breast cancer before age 55 years. Interviews and medical record reviews were used to collect risk factor and treatment histories. All women were tested for BRCA1/BRCA2 mutations. Relative (rate ratios) and absolute (5- and 10-year cumulative) risks of developing contralateral breast cancer following a first invasive breast cancer were computed.
  
  
  RESULTS
  Compared with noncarriers, BRCA1 and BRCA2 mutation carriers had 4.5-fold (95% CI, 2.8- to 7.1-fold) and 3.4-fold (95% CI, 2.0- to 5.8-fold) increased risks of contralateral breast cancer, respectively. The relative risk of contralateral breast cancer for BRCA1 mutation carriers increased as age of first diagnosis decreased. Age-specific cumulative risks are provided for clinical guidance.
  
  
  CONCLUSIONS
  The risks of subsequent contralateral breast cancer are substantial for women who carry a BRCA1/BRCA2 mutation. These findings have important clinical relevance regarding the assessment of BRCA1/BRCA2 status in patients with breast cancer and the counseling and clinical management of patients found to carry a mutation.
authors.affiliation: Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98006, USA. kmalone@fhcrc.org
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Malone
authors.forename: Colin B
authors.initials: CB
authors.lastname: Begg
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Patrick
authors.initials: P
authors.lastname: Concannon
authors.forename: Lina
authors.initials: L
authors.lastname: Tellhed
authors.forename: Shanyan
authors.initials: S
authors.lastname: Xue
authors.forename: Sharon
authors.initials: S
authors.lastname: Teraoka
authors.forename: Leslie
authors.initials: L
authors.lastname: Bernstein
authors.forename: Marinela
authors.initials: M
authors.lastname: Capanu
authors.forename: Anne S
authors.initials: AS
authors.lastname: Reiner
authors.forename: Elyn R
authors.initials: ER
authors.lastname: Riedel
authors.forename: Duncan C
authors.initials: DC
authors.lastname: Thomas
authors.forename: Lene
authors.initials: L
authors.lastname: Mellemkjaer
authors.forename: Charles F
authors.initials: CF
authors.lastname: Lynch
authors.forename: John D
authors.initials: JD
authors.lastname: Boice
authors.forename: Hoda
authors.initials: H
authors.lastname: Anton-Culver
authors.forename: Jonine L
authors.initials: JL
authors.lastname: Bernstein
mesh_terms: D000328:Adult; D000367:Age Factors; D051017:Apoptosis Regulatory Proteins; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D003718:Denmark / Q000453:epidemiology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D009154:Mutation; D009364:Neoplasm Recurrence, Local; D011159:Population Surveillance; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
chemical_list: D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human