Assessment of individuals with BRCA1 and BRCA2 large rearrangements in high-risk breast and ovarian cancer families Journal Article


Authors: Arnold, A. G.; Otegbeye, E.; Fleischut, M. H.; Glogowski, E. A.; Siegel, B.; Boyar, S. R.; Salo-Mullen, E.; Amoroso, K.; Sheehan, M.; Berliner, J. L.; Stadler, Z. K.; Kauff, N. D.; Offit, K.; Robson, M. E.; Zhang, L.
Article Title: Assessment of individuals with BRCA1 and BRCA2 large rearrangements in high-risk breast and ovarian cancer families
Abstract: BRCA1/2 large rearrangement (LR) testing has been available to patients since 2006. Three existing models commonly used in cancer genetics clinical and research settings (BRCAPRO, Penn II and Myriad II) have not been assessed for their performance in predicting the presence of BRCA1/2 large genomic rearrangements in patients who do not have mutations detectable by the traditional Sanger sequencing approach. This study sought to determine if there is an optimal pre-test probability "cut off" value, calculated using these models, to optimize detection of large rearrangements (LRs). Our cohort consisted of 3,301 probands seen for genetic counseling and BRCA1/2 clinical testing from September 2006 to September 2011. A detailed personal and three-generation family history, including self-reported ethnicity, was taken as part of our standard clinical practice. We applied the BRCAPRO, Penn II, and Myriad II models to the probands with LRs. In our cohort of 3,301 probands, 150 carried a non-Ashkenazi mutation in BRCA1 or BRCA2. Seventeen unrelated probands carried a private BRCA1/2 LR (17/150, 11.3 % of all detectable non-AJ mutations). At a pre-test probability cutoff of 10 %, all three empiric risk models would have failed to identify almost 30 % of probands with LRs. Our study shows that BRCA1/2 LR testing should be offered to all women who meet criteria for BRCA1/2 sequence analysis. © 2014 Springer Science+Business Media New York.
Keywords: adult; controlled study; aged; gene mutation; major clinical study; cancer risk; ovarian cancer; ovary cancer; breast cancer; cohort analysis; tumor suppressor gene; gene rearrangement; family history; high risk population; onset age; brca1; brca2; ethnicity; genetic counseling; human; male; female; priority journal; article; high risk family; large rearrangements
Journal Title: Breast Cancer Research and Treatment
Volume: 145
Issue: 3
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2014-06-01
Start Page: 625
End Page: 634
Language: English
DOI: 10.1007/s10549-014-2987-6
PROVIDER: scopus
PUBMED: 24825132
DOI/URL:
Notes: Breast Cancer Res. Treat. -- Export Date: 8 July 2014 -- CODEN: BCTRD -- Source: Scopus
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MSK Authors
  1. Kenneth Offit
    507 Offit
  2. Mark E Robson
    365 Robson
  3. Noah Kauff
    122 Kauff
  4. Liying Zhang
    88 Zhang
  5. Zsofia Kinga Stadler
    144 Stadler
  6. Angela Arnold
    24 Arnold
  7. Sherry R Boyar
    4 Boyar
  8. Beth   Siegel
    8 Siegel