title: Breast cancer in young women (YBC): prevalence of BRCA1/2 mutations and risk of secondary malignancies across diverse racial groups.
abstract: BACKGROUND
  Despite significant differences in age of onset and incidence of breast cancer between Caucasian (CA), African-American (AA) and Korean (KO) women, little is known about differences in BRCA1/2 mutations in these populations. The purpose of this study is to evaluate the prevalence of BRCA1/2 mutations and the association between BRCA1/2 mutation status and secondary malignancies among young women with breast cancer in these three racially diverse groups.
  
  
  METHODS
  Patients presenting to our breast cancer follow-up clinics selected solely on having a known breast cancer diagnosis at a young age (YBC defined as age <45 years at diagnosis) were invited to participate in this study. A total of 333 eligible women, 166 CA, 66 AA and 101 KO underwent complete sequencing of BRCA1/2 genes. Family history (FH) was classified as negative, moderate or strong. BRCA1/2 status was classified as wild type (WT), variant of uncertain significance (VUS) or deleterious (DEL).
  
  
  RESULTS
  DEL across these three racially diverse populations of YBC were nearly identical: CA 17%, AA 14% and KO 14%. The type of DEL differed with AA having more frequent mutations in BRCA2, compared with CA and KO. VUS were predominantly in BRCA2 and AA had markedly higher frequency of VUS (38%) compared with CA (10%) and KO (12%). At 10-year follow-up from the time of initial diagnosis of breast cancer, the risk of secondary malignancies was similar among WT (14%) and VUS (16%), but markedly higher among DEL (39%).
  
  
  CONCLUSIONS
  In these YBC, the frequency of DEL in BRCA1/2 is remarkably similar among the racially diverse groups at 14%-17%. VUS is more common in AA, but aligns closely with WT in risk of second cancers, age of onset and FH.
authors.affiliation: Department of Radiation Oncology, UMDNJ-RWJMS and Cancer Institute of New Jersey, New Brunswick, NJ 08901, USA. hafftybg@umdnj.edu
authors.forename: B G
authors.initials: BG
authors.lastname: Haffty
authors.forename: D H
authors.initials: DH
authors.lastname: Choi
authors.forename: S
authors.initials: S
authors.lastname: Goyal
authors.forename: A
authors.initials: A
authors.lastname: Silber
authors.forename: K
authors.initials: K
authors.lastname: Ranieri
authors.forename: E
authors.initials: E
authors.lastname: Matloff
authors.forename: M H
authors.initials: MH
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Nissenblatt
authors.forename: D
authors.initials: D
authors.lastname: Toppmeyer
authors.forename: M S
authors.initials: MS
authors.lastname: Moran
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics; D017668:Age of Onset; D044466:Asian People / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006801:Humans; D009154:Mutation; D016609:Neoplasms, Second Primary / Q000235:genetics; D015995:Prevalence; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein