title: Characteristics of individuals with breast cancer rearrangements in BRCA1 and BRCA2.
abstract: BACKGROUND
  Large rearrangements in BRCA1 and BRCA2 occur in a small percentage (< 1%) of patients tested for hereditary breast (BC) and ovarian cancer. It is unclear what factors predict BRACAnalysis Large Rearrangement Test (BART) positivity.
  
  
  METHODS
  Data from 6 centers were included in this analysis. Individuals with negative Comprehensive BRACAnalysis tested for BART were included.
  
  
  RESULTS
  From 1300 individuals, 42 (3.2%) were BART positivity. Factors positively associated with BART positivity were Myriad score, first-degree relatives with BC, infiltrating BC with ductal carcinoma in situ, younger age at BC diagnosis, estrogen receptor-negative BC for both the first and second BC, and Latin American/Caribbean ethnicity. Presence of unilateral BC was inversely associated with BART positivity. Several analyses were performed on the variables available to find the model that best predicts for BART positivity. The BART predictive model, including first BC, ovarian cancer, primary maternal ancestry being Latin America/Caribbean, number of first-degree relatives with BC of 1 or more versus 0, and family history of prostate and pancreatic cancer, had good predictive ability with an area under the curve of 0.77.
  
  
  CONCLUSIONS
  Several factors are significantly associated with BART positivity. Among them we have found that Latin American/Caribbean ancestry, Myriad score, first degree relatives with BC, younger age at BC diagnosis, estrogen receptor-negative status of BC, and infiltrating ductal carcinoma with ductal carcinoma in situ features are significantly associated with BART positivity. A BART predictive model may help in a clinical setting.
authors: Division of Hematology/Oncology, Robert H Lurie Comprehensive Cancer Center Northwestern University, Chicago, Illinois.
authors: Sarah A
authors: SA
authors: Jackson
authors: Andrew A
authors: AA
authors: Davis
authors: Jun
authors: J
authors: Li
authors: Nengjun
authors: N
authors: Yi
authors: Shelley R
authors: SR
authors: McCormick
authors: Carly
authors: C
authors: Grant
authors: Taya
authors: T
authors: Fallen
authors: Beth
authors: B
authors: Crawford
authors: Kate
authors: K
authors: Loranger
authors: Jennifer
authors: J
authors: Litton
authors: Banu
authors: B
authors: Arun
authors: Kimberly
authors: K
authors: Vande Wydeven
authors: Amer
authors: A
authors: Sidani
authors: Katie
authors: K
authors: Farmer
authors: Merideth
authors: M
authors: Sanders
authors: Kent
authors: K
authors: Hoskins
authors: Robert
authors: R
authors: Nussbaum
authors: Laura
authors: L
authors: Esserman
authors: Judy E
authors: JE
authors: Garber
authors: Virginia G
authors: VG
authors: Kaklamani
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics; D000328:Adult; D001741:Black or African American / Q000235:genetics / Q000706:statistics & numerical data; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000235:genetics; D018275:Carcinoma, Lobular / Q000235:genetics; D017691:Caribbean Region / Q000208:ethnology; D002352:Carrier Proteins / Q000235:genetics*; D005060:Europe / Q000208:ethnology; D005091:Exons / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D020440:Gene Duplication; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006630:Hispanic or Latino / Q000235:genetics / Q000706:statistics & numerical data; D006801:Humans; D007585:Jews / Q000235:genetics / Q000706:statistics & numerical data; D008875:Middle Aged; D009154:Mutation; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics*; D011237:Predictive Value of Tests; D012306:Risk; D014157:Transcription Factors; D014481:United States; D044465:White People / Q000235:genetics / Q000706:statistics & numerical data
chemical_list: C485676:ARL2BP protein, human; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D014157:Transcription Factors
keywords: BART; BRCA1; BRCA2; breast cancer; breast cancer rearrangement mutations; mutations