Navigation Boosts Cascade Genetic Testing in Relatives of BRCA Carriers

Facilitated cascade genetic testing with navigation support raised testing uptake among first-degree relatives (FDRs) of individuals with BRCA1/2 pathogenic variants from 50.7% to 73.2% at 6 months compared with standard care, according to results of a randomized controlled trial (NCT04613440) published in the Journal of Clinical Oncology. By 18 months, 90% of FDRs in the intervention arm had completed testing. Free germline testing was available to relatives in both arms.

"When we provided navigation to help people through the testing process, we noticed a meaningful difference in utilization and how soon people completed their testing," lead author Roni Nitecki Wilke, MD, MPH, assistant professor in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, said in a news release.

Why does cascade genetic testing matter for BRCA1/2 families?

BRCA1/2 pathogenic variants follow autosomal dominant inheritance, giving each FDR a 50% chance of carrying the familial variant. Relatives identified through cascade testing become eligible for screening and risk-reducing interventions, but uptake under the current letter-based model is low.

"The way we do it in standard of care just doesn't work and less than a third of patients actually get tested," Wilke said in an interview with Oncology Nursing News.

A prior single-institution study of clinician-facilitated cascade testing reported 58% uptake among relatives but had no standard-of-care comparator.

How was the trial designed?

Investigators cluster-randomized 151 probands with newly diagnosed BRCA1 (52%) or BRCA2 (48%) germline pathogenic variants; 72% had a prior cancer diagnosis. Randomization was stratified by personal cancer history, number of FDRs (1-2 vs ≥3), and time since genetic testing (≤6 months vs >6-12 months).

Untested adult FDRs were enrolled: 142 in the intervention arm and 144 in the control arm.

• Intervention arm: navigation support plus access to genetic testing services
• Control arm: a family letter, consistent with standard clinical practice
• Both arms: free germline genetic testing on request
• Primary end point: completion of genetic testing at 6 months

What did the trial find?

At 6 months, 73.2% (adjusted 95% CI, 64.4%-82.1%) of FDRs in the intervention arm completed testing vs 50.7% (adjusted 95% CI, 41.0%-60.4%) in the control arm (P < .001).

• Testing at 18 months, intervention arm: 90%
• FDRs who completed testing across both arms: 206
• Pathogenic or likely pathogenic variant identified: 95 of 206 (46%)
• Familial variant among those with a positive result: 82 of 95 (86%)

The control arm exceeded historical benchmarks, which Wilke attributed to study contact: staff called relatives for consent and to ask about testing, and those who requested testing received it free.

"It took two phone calls in the standard of care arm for us to show sort of higher engagement than what the literature has shown so far," Wilke said. In the intervention arm, she said, "when the navigator was truly engaged and involved," the team "got almost everyone tested, which is extremely rare for this type of intervention."

Testing also plateaued after approximately 9 months, which Wilke said "suggests that the time frame for intervention is actually not very long." The plateau, she added, "really creates a window of opportunity for us to implement these interventions to try to get as many people tested as possible."

Who can serve as a navigator?

Navigators in the trial were trained study staff, and they "don't have to be a genetic counselor," Wilke said. "In our study, these were not genetic counselors, these were just study team members that we trained."

The trial does not define how to deliver navigation outside a research protocol or academic center, which Wilke said would likely require a dedicated navigator and new workflows. Co-senior author J. Alejandro Rauh-Hain, MD, MPH, is leading a randomized trial of cascade testing in community settings.

Nurses already help identify candidates for familial testing and explain how germline testing differs from tumor testing.

What are the key takeaways for oncology nurses?

• Start outreach early. Uptake plateaued after about 9 months.
• Do not rely on the family letter alone. Wilke said fewer than one-third of relatives test under that model.
• Contact relatives directly. Control-arm relatives who received 2 study phone calls tested at rates above historical benchmarks.
• Train non–genetic counselor staff. Study team members served as navigators.
• Ask why relatives have not been tested. Wilke pointed to "a consistent conversation, having an open communication line, figuring out why people don't get testing, and really supporting them through it."
• Plan for positive results. Nearly half of tested FDRs carried a pathogenic or likely pathogenic variant and need referral for screening and prevention.

References

1. Wilke RN, Moss HA, Iniesta MD, et al. Facilitated cascade genetic testing for relatives of individuals with BRCA1/2 pathogenic variants: a randomized controlled trial. J Clin Oncol. Published online September 29, 2026. doi:10.1200/JCO-26-00735
2. Personalized support and navigation increased genetic testing of hereditary cancers among immediate family members. News release. The University of Texas MD Anderson Cancer Center. September 29, 2026. Accessed October 7, 2026. https://www.mdanderson.org/newsroom/research-newsroom/personalized-support-and-navigation-increased-genetic-testing-of-hereditary-cancers-among-immediate-family-members.h00-159858501.html
3. Frey MK, Kahn RM, Chapman-Davis E, et al. Prospective feasibility trial of a novel strategy of facilitated cascade genetic testing using telephone counseling. J Clin Oncol. 2020;38(13):1389-1397. doi:10.1200/JCO.19.02005
4. Benyon B. Nurses can help 'demystify' genetic testing results. Oncology Nursing News. November 25, 2024. Accessed October 7, 2026. https://www.oncnursingnews.com/view/nurses-can-help-demystify-genetic-testing-results