Genetic Test Underused in Cancer Care

An emerging oncology tool known as broad genomic profiling or BGP is increasingly being used to help identify targeted therapies for patients diagnosed with cancer.

Rather than analyzing one gene at a time for mutations that could be related to a patient’s cancer, BGP examines multiple genes in a tumor sample all at once. This comprehensive analysis helps health care providers better understand a tumor’s entire genetic makeup so they can prescribe targeted therapies to attack the disease.

Yet despite BGP’s potential medical benefits, a new study by researchers at the Yale School of Public Health (YSPH) finds that the BGP remains widely underused—even among certain cancers for which the test is explicitly recommended.

“The adoption of BGP has been growing, but many patients are still not necessarily undergoing testing,” said Dr. Michaela Dinan, PhD, the study’s senior author and an associate professor of chronic disease epidemiology at YSPH. Dinan is also co-leader of Yale’s Cancer Prevention and Control Research Program at Yale Cancer Center.

The researchers also found that whether patients are offered the test correlates in part with sex, age, and where they live.

“The biggest take-home point for oncologists to consider is whether BGP may be helpful for their particular patient,” Dinan said.

Using information from a large Blue Cross Blue Shield health insurance claims database, Dinan and her co-authors applied a novel algorithm to examine BGP use in over 50,000 U.S. patients diagnosed with the 10 most common metastatic cancers between 2020 and 2022. The authors documented BGP use within six months of advanced or metastatic cancer diagnosis.

Throughout the study period, about 1 in 5 patients received BGP. Its use grew more common as the years progressed, rising from 15.1% of patients early in 2020 to 24.3% by mid-2022.

Despite this growth, the researchers found that the BGP test was underused in all cancers, with well under half of the patients tested in most cancer categories. This pattern held even for patients with lung, pancreatic, melanoma, and breast cancers, for which BGP is explicitly recommended under National Comprehensive Cancer Network (NCCN) guidelines. Lung cancer saw the highest use of BGP at 49%. BGP tests were used more often for suspected kidney cancer—for which BGP is not routinely recommended—than breast cancer, the study revealed.

“In lung cancer, we've gotten to the point where it should be the standard of care across the board,” said Dr. Xiao Wang, the study’s lead author and a clinical fellow in the medical oncology and hematology unit in the Department of Internal Medicine at Yale School of Medicine (YSM). The finding of 49% is “lower than we would expect,” he said.

Potential reasons for the testing disparities varied, according to the authors. Older age, frailty, female gender identity, and living anywhere but the Northeast were all associated with a lower likelihood of broad genomic profiling.

“Most diagnostic tools and treatments are often somewhat less likely to be used in older patients, since some older patients may have competing health issues or other reasons to pursue treatment less aggressively,” Dinan said. “The association with female sex was not expected and is something we hope to look into more in the future.”

By detecting gene alterations relevant to a patient’s cancer, BGP may point the way to clinical trials or to tailored treatments that depend on the mutated gene rather than the cancer type. The test may also tip physicians off to a more aggressive cancer.

Routine use of BGP has been recommended for over a decade for patients with lung cancer, for which there are nearly a dozen treatment therapies targeting different gene alterations. For patients with breast cancer, BGP tends to be more influential for second-line treatment decisions, the authors said.

In the past, Wang said, “we might test for genomic alterations individually. But as we've accumulated more and more [knowledge], we've used these broad genomic profiling platforms to test for dozens or even hundreds of genes or alterations simultaneously.”

Though it’s more comprehensive than single-gene tests, BGP is potentially slower and more expensive.

The study has some limitations. The authors note that it was conducted only among privately insured patients; the results might differ in other populations.

Wang cautioned against concluding that patients without a documented BGP received substandard care. The authors focused on BGP testing shortly after diagnosis; some patients may have gotten the test later on.

“If a patient is not going to benefit from getting the test, if it's going to take three weeks to get the test, and single gene testing can come back within a couple of days, I definitely can understand why an oncologist might forgo this type of testing,” Wang said. “That just speaks to the fact that we need to improve access for those patients and make it feasible and effective for those patients to get BGP as well.”

The study is the first in a forthcoming series of Yale-led studies that will examine the use of BGP in U.S. cancer care. Future studies will address its effects on treatments and outcomes and whether it is cost-effective.

“You can imagine that over time, as tests get faster and cheaper and we develop more and more treatments with more and more targets, that [BGP] might be more beneficial,” Wang said. “It's a really powerful tool, and we want to understand how we can best use it for our patients.”

The study appears in JAMA Oncology. Funding was provided by the National Institutes of Health.

In addition to Wang and Dinan, other authors on the study were Sarah B. Goldberg, also of the YSM Department of Internal Medicine’s Section of Medical Oncology; John Rothen, Jessica B. Long, and Pamela R. Soulos of YCC’s COPPER Center; Sida (Stark) Huang, a YSPH student; Ronac Mamtani of the University of Pennsylvania’s Perelman School of Medicine; Carolyn J. Presley of The Ohio State University; Natalia Kunst of the COPPER Center and the University of York; Shuangge Ma of YSPH; Shi-Yi Wang, an affiliate of COPPER and YSPH; and Cary Gross of COPPER, YSPH, and YSM’s Department of Internal Medicine.