A facilitated approach to cascade genetic testing can significantly increase uptake among at-risk relatives of people with newly diagnosed BRCA1/2 mutations, a randomized trial found.

Cascade genetic testing, where testing is offered to relatives of patients with known cancer susceptibility genes, has the potential to prevent a substantial number of cancers or allow for early detection. However, current practice relies on patients to inform their family members about testing.

In the new trial, researchers evaluated a facilitated approach that shifts responsibility to the medical team. They found that at 6 months, nearly three quarters of first-degree relatives in that facilitated group completed genetic testing vs about half of the control group, who were tested under current practice.

The results support a “paradigm shift to facilitated cascade testing,” said lead researcher Roni Nitecki Wilke, MD, MPH, of The University of Texas MD Anderson Cancer Center in Houston.

She presented the findings in a plenary session at Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer 2026.

Addressing a Missed Opportunity

It’s estimated that 16 million Americans have a hereditary predisposition to cancer, but only a fraction of these individuals have been diagnosed — in what Wilke called a “critical missed cancer prevention opportunity.”

Population-based testing for hereditary cancer risk has not been shown to be cost-effective and is not recommended by the US Preventative Services Task Force. Cascade genetic testing, which essentially targets the highest-risk population, is considered a promising alternative.

“It is accepted that if broadly implemented, cascade genetic testing can reduce the burden of hereditary cancer,” Wilke said. “But it's not clear how to best implement this in clinical practice.”

Current standard practice relies on patients with known pathogenic variants to notify relatives through a family letter. But this approach has consistently fallen short, with only about 30% of at-risk relatives completing genetic testing.

Why? Wilke put it this way: “Imagine a patient with newly diagnosed ovarian cancer. She has a biopsy, imaging. She has chemotherapy, surgery. She has to juggle work responsibilities, financial responsibilities. Then she’s found to be a BRCA carrier. So now as part of the standard of care, she’s expected to contact her family, explain complex genetics, and arrange cascade genetic testing.”

“It’s clear,” Wilke said, “why this may not be the first thing on her to-do list.”

To test an alternative, facilitated strategy, her team randomly assigned 151 patients with BRCA1/2 pathogenic variants to an intervention group (n = 72) or control group (n = 79).

In the facilitated group, 142 first-degree relatives received telephone-based genetic navigation and access to free, at-home saliva testing. In the control group, 144 first-degree relatives were contacted through the traditional family letter but still had access to free genetic testing.

The facilitated approach significantly increased rates of cascade genetic testing. At 6 months, 73% of relatives in the intervention group completed genetic testing compared with 51% of those in the control group (P < .001). By 18 months, about 90% of relatives in the intervention group had completed testing.

Nearly half of the tested relatives were found to carry a pathogenic variant, prompting many to take “meaningful clinical action,” Wilke reported.

About half of the women found to have a BRCA mutation established care with a provider, and six underwent risk-reducing surgeries.

Translating to the Real World

Wilke said the findings point to a possible new standard of care. She acknowledged, however, that “scalable models” are needed to figure out how to best implement the facilitated approach in routine clinical practice.

If it does become the norm, it could have a bigger impact than this trial suggests, according to study discussant Bradley Corr, MD, a gynecologist oncologist with UCHealth Cancer Care, in Aurora, Colorado.

He noted that even though half of the control group underwent testing — well above the 30% historical rate — the clinician-driven approach still had a substantial effect.

“Screening for this trial alone likely increased the rate of compliance,” Corr said. “So seeing the magnitude of benefit over the control group is outstanding.”

In the real world, where testing rates are lower, he said, the benefits are likely to be even greater.

This study received no commercial funding, and Wilke had no disclosures. Corr reported serving as an advisor to BioNTech, GSK, Gilead, and other companies.