Could Early Exome Sequencing Improve Detection and Prevention of BRCA1/2 Breast Cancer?
BACKGROUND AND PURPOSE:
Manickam et al. (JAMA Network Open, 2018) sought to identify significant disease-causing BRCA1/2 variants and their associated features
Cross-sectional study of adult volunteers who underwent exome sequencing at a single health care system
Participants underwent sequencing and return of actionable test results
Pathogenic and likely pathogenic (P/LP) variants
Clinical data from electronic health records and clinical visits were correlated with variants
Comparisons were made between those with P/LP variants in BRCA1/2 (cases) and those without (controls)
50,726 participants were included in the study
50,459 (99.5%) had no expected pathogenic BRCA1/2 variants
267 (0.5%) were BRCA1/2 carriers
148 [55.4%] were women
183 (68.5%) received clinically confirmed results in their electronic health record
Among the 267 participants with P/LP BRCA1/2 variants
219 (82.0%) had no prior clinical testing
95 (35.6%) had BRCA1 variants
172 (64.4%) had BRCA2 variants
56 (20.9%) had syndromic cancer diagnoses
Among women, personal history of breast cancer was present in
Variant carriers: 31/148 (20.9%)
Noncarriers: 1554/29,880 (5.2%)
Odds ratio (OR), 5.95 (95% CI, 3.88-9.13; P < .001)
Among women, ovarian cancer history was present in
Variant carriers: 15/148 (10.1%)
Noncarriers: 195/29,880 (0.6%)
OR 18.30 (95% CI, 10.48-31.4; P < .001)
Among 89 BRCA1/2 carriers without prior testing, 44 (49.4%) did not meet published (NCCN) guidelines for clinical testing
Compared with previous clinical care, exome sequencing–based screening identified 5 times as many individuals with P/LP BRCA1/2 variants
Only 17.9% of BRCA1/2 carriers had BRCA1/2 testing as part of their health care
Genomic screening may identify BRCA1/2-associated cancer risk that might otherwise remained undetected
The authors state
The prevalence of BRC1/2 variants in the general population may be substantially higher than was previously estimated, and reliance on personal and family history may be an inadequate measure to ascertain risk for BRCA1/2 variants.
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