Low Uptake of Cascade Germline Testing in Cancer Represents a 'Public Health Emergency,' Experts Warn

Most patients with cancer who carry germline mutations overwhelmingly recognize the importance of notifying relatives about shared genetic risks, yet systemic failures in the health care system have left cascade testing rates dangerously low—a situation one leading researcher has labeled a "public health emergency."

A survey of nearly 2,000 patients with genetic variants predisposing them to cancer, conducted by researchers at Stanford University School of Medicine查看公司主页, revealed that almost 90% viewed sharing results as their responsibility and notified their first-degree family members. However, nearly 30% of patients reported that none of their relatives got tested, and many families experienced only partial uptake of cascade genetic testing.

"Testing is too low, testing rates of relatives are too low, and that is a public health emergency, because testing can save lives," said Allison W. Kurian, MD, MSc, professor of medicine and epidemiology and population health at Stanford University School of Medicine查看公司主页. "Patients want to help their relatives get tested, and there is a gap in terms of what they receive from the health care system. Anything we can do to close that gap through speaking with patients, through offering resources for education and testing, is key."

The Scope of the Problem

Inherited germline mutations are estimated to cause between 5% and 10% of all cancers, according to the National Cancer Institute. Yet in 2023, Kurian and colleagues published data in JAMA showing that less than 7% of eligible patients undergo genetic testing.

"If patients test positive, we ask them to notify their relatives," Kurian explained. "We would like for nearly 100% of relatives of somebody who has a genetic mutation to get tested themselves through this cascade process, but most studies have shown that the rate that actually get tested is not very high, in the range of 30%. Cascade testing is a huge and missed opportunity to save lives through early detection and risk assessment in cancer."

Kurian and colleagues surveyed all adults diagnosed with their first cancer in 2018 or 2019 in the Georgia-California SEER Genetic Linkage Initiative. The final sample included 1,944 patients—88.6% women and 64.3% white—with links to any of 28 pathologic variants. Genetic mutations were categorized as relating to either breast cancer (搜索)搜索该疾病 (83.4%) or gastrointestinal cancer (搜索)搜索该疾病 (16.6%). The survey, conducted 4.5 years after diagnosis, assessed clinician involvement in communication with relatives, patient attitudes about informing family, and how many relatives ultimately underwent testing.

Clinician Engagement Varies Widely by Specialty

A striking finding was the disparity in how different clinical specialties engaged with patients about cascade testing. While 71% of patients reported that genetic counselors encouraged them to speak to relatives about testing, only about one-third said medical oncologists did the same. Cancer surgeons had even lower rates: just 19% encouraged such discussions, 9% provided advice on how to discuss the topic, and only 7% spoke with relatives directly.

By comparison, 55% of patients said genetic counselors gave them advice on how to discuss the topic, and 33% reported counselors spoke with relatives themselves.

"What clinical specialty owns this problem?" Kurian asked. "In many ways, cascade testing is a perfect example of challenges in our medical system. This is a problem not just for the patient sitting in front of the doctor or genetic counselor—it is for the whole family. Our medical system doesn't deal with the whole family."

Kurian noted structural barriers including different insurance coverage among family members, state-based medical licensing restrictions, and privacy regulations that limit clinicians from directly contacting a patient's relatives. "The challenge is, nobody is incentivized. Nobody has a sense that it is truly their responsibility to be thinking about relatives. The doctor seeing the patient is not getting reimbursed or encouraged to think about the family."

Patient Attitudes and Testing Outcomes

Despite systemic obstacles, patients demonstrated strong personal commitment to informing relatives. About three-quarters of respondents said they understood testing results well enough to have discussions with relatives, 88% reported relatives found the results "useful," and nearly 88% said they viewed sharing results as their responsibility. Roughly 87% of patients told their first-degree relatives, and nearly 45% informed second-degree relatives.

"I was happy to see that," Kurian said. "It is encouraging that people feel responsible for their family, that people understand the public health imperative and want to do the right thing, to take care of their family members."

However, the translation from communication to completed testing showed significant drop-off. Among respondents who provided relative testing results, 29% said no relatives got tested, 22.7% reported one relative got tested, 30.1% said two or three underwent testing, and only 18.3% reported four or more relatives completed genomic testing.

"For 29%, no one got tested, and that's a concern," Kurian said. "For example, 62% of respondents said they had four or more first-degree relatives alive, but only 18% said four or more relatives got tested. There is a drop-off. I think patients are trying very hard. They get it. Relatives may not have heard the message, or they may have heard it but not known how to get testing done logistically, or been concerned about cost or privacy."

Estonian Data Reinforce the Value of Early Testing

Complementary findings from Estonia underscore the clinical value of cascade testing. Researchers reviewing genetic testing results from 3,472 healthy family members of breast and ovarian cancer (搜索)搜索该疾病 patients tested between 2007 and 2023 found that 19.7% carried pathogenic variants that elevate cancer risk. Among male participants, 34% tested positive for at least one variant.

"Hereditary cancer risk is both more common and more actionable than often assumed," said Dr. Mikk Tooming of the Institute of Clinical Medicine in Tartu, Estonia, lead author of the study published in Frontiers in Genetics. "People with a family history of breast or ovarian cancer (搜索)搜索该疾病—especially those with multiple affected relatives or early-onset cases—should strongly consider genetic counselling and, where appropriate, genetic testing."

The Estonian cohort was 87.6% women and 12.4% men, with a mean age at testing of 41—ten years younger than Estonia's standard cancer screening age. Notably, 78.6% of those tested were even younger, and people under 30 were most likely to test positive for pathogenic variants. Among participants with a known familial variant, 41.8% carried a relevant variant themselves. Among the remaining two-thirds without a known familial variant, 8% still carried pathogenic variants.

"Our study also highlights that men should not be overlooked," Tooming added. "Male carriers of pathogenic variants, particularly in BRCA2 (搜索)搜索该靶点, face increased risks for prostate and other cancers, and may benefit from earlier and more targeted screening."

Closing the Gap with Novel Interventions

To address the cascade testing gap, Kurian and colleagues developed the Genetic Information and Family Testing (GIFT) online platform. A study evaluating GIFT showed that 32% of invited relatives enrolled, and 91.3% of that group underwent genetic testing.

"The GIFT trial helped patients reach out to their relatives more effectively, and get education and testing into relatives' hands," Kurian said. "We have a study opening that will test this approach in clinics, which is very exciting. This is all about moving the numbers, because there has been a real challenge in getting cascade numbers above 50%. Our work aims to develop strategies that close the cascade testing gap, get relatives tested and point them to effective follow-up care."

The Estonian researchers similarly emphasized the need for systemic change. "The results support earlier genetic risk assessment rather than simply lowering screening age thresholds," Tooming said. "They also strongly support broader and more systematic genetic testing among relatives, particularly when a familial pathogenic variant is identified. The relatively high detection rate we observed, including among individuals without a previously known familial variant, suggests that broader access to multigene panel testing could improve identification of at-risk individuals."

Researchers on both studies acknowledged limitations. The U.S. survey relied on patient recall 4.5 years after diagnosis, and patients may not have known the full scope of testing in their families. The Estonian analysis noted that changes in testing quality and accessibility over time—including the introduction of next-generation sequencing after 2015—could affect findings, and more research is needed to understand prevalence in other populations.