Abstract A34: How important is comprehensive rearrangement testing for BRCA mutations in African American women with early-onset breast cancer?
Authors: Pal Tuya , Bonner Devon , Akbari Mohammad , Narod Steven , Vadaparampil Susan 
Published: August 2014

Abstract
Background: Young Black women are disproportionately afflicted with breast cancer, a proportion of which may be due to BRCA1 and BRCA2 (BRCA) gene mutations. Deleterious mutations in the BRCA genes include those identified by sequencing technology as well as large genomic rearrangements that are found with different technologies (i.e., multiplex ligation-dependent probe amplification (MLPA)). The sole provider of clinical BRCA genetic testing in the United States is Myriad Genetics Laboratories, the company which owns the patent on these genes. When BRCA testing is ordered through this company, the standard test is called ‘Comprehensive BRCAnalysis’, which includes BRCA sequencing and testing for five rearrangements in BRCA1. In addition, testing for large rearrangements has been available since 2006, but is ordered and billed as a separate test from Comprehensive BRCAnalysis (at a cost of $700, often as an out-of-pocket expense).
Objectives: In a cancer registry-based sample of Black women with early onset breast cancer, we evaluated prevalence of: 1) BRCA mutations; and 2) individuals who had BRCA testing (+counseling) predating study enrollment.
Methods: Black women diagnosed with invasive breast cancer &lt; age 50 in 2009-2010 were recruited through the Florida Cancer Registry utilizing state-mandated recruitment methods. Participants completed genetic counseling and a comprehensive risk factor questionnaire which included uptake of clinical BRCA testing pre-dating study enrollment. All participants consented to medical record release, including release of prior genetic test results. Saliva specimens were collected and BRCA testing was performed on all individuals through full gene sequencing and comprehensive rearrangement testing.
Results: Of the first 48 participants in whom results of genetic testing are currently available through the study, two mutations in the BRCA genes were detected. Both mutations were identified in women who had undergone comprehensive BRCAnalysis pre-dating study enrollment. This included one participant identified to have a deleterious BRCA2 mutation through prior clinical testing (BRCA2 exon11 5844del5), in whom the same mutation was detected through the study. The second mutation was identified through comprehensive rearrangement testing (BRCA1 delExon8) in a woman who had previously had clinical BRCA testing during her breast cancer treatment in whom no mutation was detected through ‘Comprehensive BRCAnalaysis’. Of note, 15 women overall (31.3%) had clinical BRCA testing pre-dating study enrollment, which included both women identified as mutation carriers.
Conclusions: Our findings suggest that it is critical to offer comprehensive rearrangement testing as part of BRCA testing in African American women, as one of the two mutations identified in our study was only identified through MLPA. Furthermore, in contrast to prior publications which suggest low uptake of BRCA testing in African American women, our results suggest reasonable uptake of BRCA testing in a registry-based sample of African American women with rates comparable to that previously reported in White women.
Citation Format: Tuya PalDevon Bonner, Mohammad Akbari, Steven Narod, Susan Vadaparampil. How important is comprehensive rearrangement testing for BRCA mutations in African American women with early-onset breast cancer? [abstract]. In: Proceedings of the Fifth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2012 Oct 27-30; San Diego, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(10 Suppl):Abstract nr A34.