What was the prevalence of germline genetic testing among patients diagnosed with cancer in California and Georgia between 2013 and 2019?

By Neha MathurJun 8 2023Reviewed by Danielle Ellis, B.Sc.

In a recent article published in the JAMA Network, researchers performed an observational study to determine the prevalence of germline genetic testing among all patients aged 20 years or older diagnosed with cancer between January 1, 2013, and March 31, 2019, in two United States (US), California and Georgia.

All the study participants were associated with four laboratories in these two US states performing genetic testing, and the authorities documented the results obtained in statewide Surveillance, Epidemiology, and End Results (SEER) registry data. Thus, the study analytic dataset comprised linked SEER registry variables.

Background

Practice guidelines recommend germline genetic testing, in which inherited deoxyribonucleic acid (DNA) is sequenced, for patients diagnosed with cancer to facilitate personalized genetic treatment for their cancer. An example of genetically targeted therapy is poly(adenosine diphosphate–ribose) polymerase inhibitors. Also, genetic testing could help identify relatives who might benefit from cancer screening and improve their treatment outcomes.

Guidelines strongly recommend germline testing for cancer patients with gynecological cancers, e.g., breast and ovarian cancers. It is also recommended for other cancers, like pancreatic, rectal, and prostate cancers. With recent advancements in DNA sequencing technology, testing for several types of genes has become feasible, and its financial cost has also decreased. However, studies have barely explored the benefits of germline genetic testing in patients diagnosed with cancer.

About the study

In the present study, researchers used logistic regression modeling to analyze germline genetic testing trends, including its rates and results within two years of a cancer diagnosis. They combined results from all four laboratories for the analysis, which comprised 107 tested genes. Next, the researchers categorized genes per their primary cancer association.

Finally, they evaluated the results of each gene sequencing, including allelic variants associated with augmented cancer risk, i.e., pathogenic, and variants whose association with cancer risk was unknown, i.e., uncertain. Though the researchers evaluated testing for all cancer types in the SEER site, they focused on eight types of cancers, e.g., ovarian, pancreatic, and prostate.

Results

In the two-year study duration, 93052 of 1369602 patients diagnosed with cancer underwent genetic testing, i.e., only 6.8%. Genetic testing rates surged over time but remained far below 100% in 2021 for most cancer types. In addition, the racial and ethnic inequities in germline genetic testing persisted throughout 2021 in Asian, Black, and Hispanic patients but not in non-Hispanic White patients.

These disparities were largest for three cancer types, male breast, female breast, and ovarian cancers. To address these inequities in testing, the authors recommended several strategies, for instance, engaging genetic counselors in oncology and making clinicians aware of these disparities, to name a few. Together, these study results highlighted, similar to clinical trials, that low rates of germline genetic testing might contribute to higher cancer mortality rates.

Population frequencies of pathogenic genetic germline testing results in Lynch syndrome and BRCA1/2 are comparable. However, testing rates for the two syndromes markedly varied. Accordingly, testing rates were higher for breast and ovarian cancers than colorectal and endometrial cancers (26%\38.6% vs. 5.6%\6.4%). Thus, it is crucial to target and improve testing for Lynch syndrome–associated cancers.

Further, the authors noted that germline genetic testing rates did not vary by cancer stage, which, in turn, reflected inadequate testing of patients with advanced-stage cancers and not offering testing to their relatives at high-risk. Studies have shown the benefits of poly(ADP-ribose) polymerase inhibitors in multiple cancer types. Thus, testing rates increased over time, especially for patients with pancreatic cancer, from 1.2% to 18.6% between 2013 and 2019.

A logistic regression model showed that testing rates were lower in older patients. Further, it showed that the modeled testing rates exceeded 50% for male breast cancer. However, the testing probability for ovarian and female breast cancers remained at 36% and 22%.

Furthermore, the study results highlighted the importance of panel testing of multiple genes in all cancers to facilitate the detection of pathogenic results in diagnosis-concordant and disconcordant genes, as it might facilitate customized, risk-adapted care. Conversely, preventive surgeries mis- or ill-manage cancer patients with uncertain results, whose rates are higher during germline genetic testing. Also, uncertain results are common among patients from Asian and Black communities.

Conclusions

In the future, underrepresented races and ethnicities must get more access to clinical testing and genetics research. As the cost of germline genetic testing declines and its insurance coverage increases, it will bring down the barrier that out-of-pocket costs present to testing.