Majority of Patients Unaware of their BRCA Status

Eight in 10 patients carrying a BRCA mutation are unaware of their status, according to a study published Sept. 21 in JAMA Network Open. The authors say these findings highlight that previous BRCA prevalence estimates may be low and that current risk-based methods to identify BRCA variant carriers may be inadequate.

"Our reliance on a documented personal or family history as a trigger to offer testing is not working," said senior author Michael Murray, M.D., in a statement. "Hopefully one day, we can change that with effective DNA-based screening for everyone."

Researchers analyzed data from 50,726 adult volunteers who underwent exome sequencing at Geisinger Health System (Danville, Penn.) from Jan. 1, 2014, to March 1, 2016 as part of the Geisinger MyCode Community Health Initiative's DiscovEHR cohort. Patients with pathogenic or likely pathogenic BRCA1/2 gene variants were subclassified based on prior identification of a variant and a personal or family history that would have met established clinical criteria for referral or testing.

The researchers found that 99.5 percent of patients had no expected pathogenic BRCA1/2 variants, while 0.5 percent were BRCA1/2 carriers. Among women, 20.9 percent of 148 variant carriers had a personal history of breast cancer and 10.1 percent had an ovarian cancer history versus 5.2 percent and 0.6 percent of the 29,880 noncarriers, respectively. Syndromic cancer diagnoses were present in 11 of the 23 deceased BRCA1/2 carriers and in 56 of all 267 BRCA1/2 carriers.

Among the 267 participants with pathogenic or likely pathogenic BRCA1/2 variants, 82.0 percent had no prior clinical testing and of the 89 BRCA1/2 carriers without prior testing, but with comprehensive personal and family history data, half did not meet published guidelines for clinical testing. Of the BRCA carriers that did meet current testing criteria, half not received testing.

"Substantial infrastructure and health care practitioner collaboration were necessary to support the disclosure and follow-up care of the 183 participants whose biobank consent form allowed for clinical reporting," writes Murray and colleagues. "Consistent with the vision of learning health care systems, this disclosure and follow-up approach is being informed and improved by ongoing feedback from biobank participants, health care practitioners, and researchers … and can be used as a template for other settings where the genome-first care model is implemented."

Takeaway: Given the clinical under-ascertainment of BRCA variant carriers due to the failure to apply risk-based testing strategies and the failure of these strategies to identify all true carriers, there are increasing calls for population-based BRCA screening.