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Universal genetic testing feasible at time of pancreatic cancer diagnosis

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August 31, 2018

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Randall Brand

The prevalence of pathogenic germline variants associated with pancreatic ductal adenocarcinoma and limitations of current methods to determine testing eligibility may warrant universal germline genetic testing at the time of diagnosis, according to a study of a consecutive cohort.

Full genetic testing may identify actionable genetic mutations among patients who would not have been tested under current guidelines, and also may identify future cancer risks for family members.

“As a clinician, I am quite cognizant of the suboptimal documentation regarding family cancer history obtained by physicians,” Randall Brand, MD, academic director of the gastrointestinal division at University of Pittsburgh Medical Center Shadyside and the director of Gastrointestinal Malignancy Early Detection, Diagnosis & Prevention Program, told HemOnc Today. “As a physician who runs our hereditary gastrointestinal tumor clinic, I am also aware that the best yield for genetic testing is with the individual who is diagnosed with the cancer.

“Due to the poor survival rates with pancreatic cancer, it is imperative that we approach these patients sooner rather than later,” Brand added. “That is why we took the approach of proving that patients can undergo genetic testing when they are newly diagnosed.”

Brand and colleagues enrolled consecutive adults (aged 18 to 89 years) with pancreatic ductal adenocarcinoma diagnosed in the previous 12 weeks. The final analysis included 298 patients (median age, 68.5 years; 53.7% men) across three centers.

About 70% of patients had a first-degree relative with cancer and 8% had a first-degree relative with pancreatic ductal adenocarcinoma.

“In the era of precision medicine, knowing whether an individual has a genetic susceptibility to pancreatic cancer can be used to develop strategies for cancer prevention, early detection and treatment,” Brand and colleagues wrote. “Surveillance is currently reserved for those at highest risk because of either a known hereditary cancer syndrome associated with pancreatic ductal adenocarcinoma or a family history consistent with familial pancreatic cancer, which is defined as a family with at least two first-degree relatives with pancreatic ductal adenocarcinoma.”

Researchers assessed the prevalence of pathogenic germline variants in 32 cancer susceptibility genes.

Researchers observed clinically actionable variants among 29 patients (9.7%), with 23 patients (7.7%) having variants associated with an increased risk for pancreatic ductal adenocarcinoma and six patients (2%) harboring variants in cancer susceptibility genes not previously recognized as associated with pancreatic cancer.

ATM (3.3%) and BRCA1/BRCA2 (2.7%) appeared to be among the frequently mutated genes in the cohort.

A greater proportion of patients with pathogenic germline variants had a personal history of cancer (37.9% vs. 17.5%; P = .013) and had at least one first-degree relative with cancer (89.7% vs. 68.4%; P = .007) than those without variants.

“Our findings suggest that about 10% of patients unselected by personal or family history of pancreatic cancer will have a pathogenic variant that is clinically actionable,” Brand said. “The term ‘clinically actionable’ implies that the findings can either be used for treatment decisions for the patient themselves or, if a family member is found to carry the mutation, lead to changes in cancer screening for that family member.”

Of the 23 patients with pancreatic cancer-associated pathogenic germline variants, six (26%) did not meet current guidelines for genetic testing.

In the context of guideline-based genetic testing, researchers determined only 11 of the 23 (48%) germline variants known in pancreatic ductal adenocarcinoma would have been detected.

“Our results add to existing evidence demonstrating the limitations of genetic testing criteria for identifying actionable mutations in cancer patients,” the researchers wrote. “If adherence to clinical testing guidelines is a prerequisite for germline testing, patients with pancreatic ductal adenocarcinoma are among those with the highest prevalence of undetected actionable germline mutations.”

Those carrying mutations appeared more likely to meet at least one criterion for hereditary breast and ovarian cancer genetic testing (72.4% vs. 37.9%; P < .001) than noncarriers.

“The yield for genetic testing for any one individual gene is not high enough to warrant genetic testing; however, if all known pancreatic cancer-associated susceptibility genes are performed simultaneously, the yield is quite good — at 10% — and reaches a threshold that is clinically beneficial,” Brand told HemOnc Today.

Despite the potential benefits of universal genetic testing, there are several challenges with the implementation, Brand said. The biggest of them includes a “lack of trained personnel to counsel patients about genetic testing and the need to ensure that test results are followed up appropriately,” he said.

“Our center, along with others, are exploring how to better implement universal testing,” he added. “This could include a general overview of genetic testing by a prerecorded presentation, followed by a meeting with trained genetic professionals for those individuals with a positive test.” – by Cassie Homer

For more information:

Randall Brand, MD, can be reached at Department of Medicine, University of Pittsburgh Medical Center, 5200 Centre Ave., Suite 409, Pittsburgh, PA 15232; email:

Disclosures: Brand reports Invitae provided free genetic testing for a study cohort in a different study. Other authors report employment with Ambry Genetics, which provided genetic testing for the study. Please see the study for all other authors’ relevant financial disclosures.


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