NEW YORK – Although population screening for cancer-related founder mutations in BRCA1/2 in individuals with Ashkenazi Jewish ancestry is possible in American cities, new research suggests there are still hurdles when it comes to reaching participants and their healthcare providers.
"Offering targeted testing for the BRCA mutations in the Ashkenazi Jewish community provides the opportunity to establish a digital health model that may aid in the implementation of broader testing in this community and potentially others," Kelly Morgan, a genetic counselor at Memorial Sloan Kettering Cancer Center, said at the American Society of Clinical Oncology's virtual annual meeting, while presenting findings of the BRCA Founder OutReach (BFOR) Study. However, the study also flagged provider reluctance and community engagement as challenges to expanding rollout of such programs.
In BFOR, researchers aimed to understand BRCA founder mutation testing uptake and impacts in Ashkenazi Jewish individuals — from participation rates and results to related interactions between participants and their local healthcare providers.
Roughly one in 40 individuals of Ashkenazi Jewish descent carry one of the three founder mutations in BRCA1 and BRCA2, which were identified in this ancestry group in the mid-1990s, Morgan explained.
Although earlier studies have demonstrated the feasibility and safety of BRCA testing in this group, Morgan noted that "further research is needed to understand the potential implementation of this testing in a variety of healthcare systems."
Following from studies done in Canada, Israel, and the UK, she and her colleagues set out to explore the feasibility of doing population screening for the founder mutations in the US in the BFOR study. "While testing was provided at no cost, insurance was required to ensure that participants had access to medical follow up as needed," Morgan noted.
The work was led by investigators at MSK, the University of California at Los Angeles David Geffen School of Medicine, the Dana-Farber Cancer Institute, Beth Israel Deaconess Medical Center, and the University of Pennsylvania's Basser Center for BRCA.
The team enrolled eligible participants in the New York/New Jersey metro area, Boston, Philadelphia, and Los Angeles over two years — from March 2018 to March 2020 — using community outreach, including informational talks and community events; social media, email, and television advertising; media articles; and partnerships established with leaders from local Jewish communities.
Those who enrolled in the study completed online registration, education, questionnaires, and consent steps before having a blood draw and testing at local Quest Diagnostics Patient Service Centers. For a subset of BFOR participants who signed up more recently, the team also assessed the feasibility of saliva-based BRCA1/2 testing.
Along with findings from these tests, the team advised founder mutation-free participants deemed at high risk to seek further genetic testing, as appropriate. Those individuals were identified with the help of an algorithm that incorporated the National Comprehensive Cancer Network's guidelines and participants' personal and family histories provided upon enrollment.
The participants' results were returned to them by a genetic counselor from the study, or by their own primary care providers. Related medical care stemming from the test results, such as preventive screening, was done through the individuals' local providers.
In an effort to boost providers' engagement with the study, the individuals could also nominate their primary care providers to receive and communicate the BRCA1/2 test results. Those providers were invited to participate in the study through surveys done at baseline and after results were returned, and those who opted into the study received resources to help them discuss the genetic results with their patients.
As it turned out, fewer than one-third of participants tested chose to have results returned by their primary care providers, though older participants tended to select this option as did those with primary care providers who had recommended genetic testing to them.
Primary care providers often appeared less than keen to participate: just over 40 percent of those nominated by patients participating in BFOR agreed to disclose the BRCA1/2 test results.
"Ultimately, a minority of results were disclosed by [primary care providers] due to both participant and provider preference," Morgan said during her presentation.
She noted that the majority of the 5,194 Ashkenazi Jewish individuals who registered for BFOR — nearly 78 percent — were female, and well over half appeared to have relatively low cancer risk based on their family histories.
As of early March, 4,071 had completed testing, and 265 participants had tests pending. The remaining 858 individuals were lost to follow up before completing registration or blood draw steps, though individuals who got as far as completing consent for the study were more likely to proceed with testing. Older individuals were less likely to be lost to follow up than their younger counterparts, the team found, as were individuals with a known mutation in their family.
Among those tested so far, the team identified founder BRCA1/2 mutations in 137 individuals, or 3.4 percent of those tested. More than 60 percent of those individuals had a familial mutation, Morgan noted, though individuals with high-risk family histories, men, participants without children, and those reporting cancer-related distress in baseline surveys were also over-represented in the group testing positive for founder mutations.
More than two-thirds of the individuals with founder mutations said they expected to undergo increased cancer screening, including prostate screening in the male participants, or had already explored surgical options such as mastectomy or oophorectomy to reduce their cancer risk.
In additional analyses of participation rates along each step of the BFOR study, the researchers reviewed results from surveys completed at baseline, three months after test result disclosure, and annually for up to five years. One of the findings from these surveys was that just 3.6 percent of individuals who were negative for a founder mutation but at high overall risk had not gone on to do additional genetic testing, despite recommendations from the study team.
Morgan noted that still other analyses are underway to look more closely at primary care provider experiences, impressions, and impacts in the study, and to explore the psychosocial impacts of founder mutation testing on participants.
From their results so far, she said, the team believes BRCA screening is feasible in the Ashkenazi Jewish population in the US. Even so, "there are substantial challenges, including community outreach, provider participation, medical follow-up, and laboratory testing and logistics."
"I would agree with that conclusion," said Maryland Oncology Hematology's Carolyn Hendricks, who discussed the BFOR study as part of a highlights session on care delivery and regulatory policy at the ASCO conference on Sunday. More broadly, she called BFOR a powerful multicenter study that has managed to utilize digital outreach and tools in germline testing.