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We're at the 'Tip of the Iceberg' in Genetic Testing for Pancreatic Cancer


Genetic testing is becoming more important in pancreatic cancer, especially since it can point toward more efficacious treatment regimens for some patients.

As more molecular abnormalities are studied in patients with pancreatic cancer, treatment options may eventually shift to a more targeted and personalized approach, according to Diane M. Simeone, M.D., director of the Pancreatic Cancer Center at NYU Langone’s Perlmutter Cancer Center in New York.

“Now we understand that there are some emerging subtypes of pancreatic cancer that we want to think about treating differently,” Simeone said in an interview with OncLive, a sister publication of CURE.

Molecular abnormalities that are emerging in the field include BRCA1 and BRCA2, ATM, CHEK2 and microsatellite instability (MSI). Simeone recommends that all patients diagnosed with pancreatic cancer undergo genetic testing.

“We perhaps underappreciate the presence of germline mutations in pancreatic cancer and we should do more comprehensive germline analyses; every patient with pancreatic cancer should get a germline analysis,” she said. “Then, we will have a much higher likelihood of identifying individuals who have the disease at an earlier stage, increase our resectability rates and increase overall survival.”

A germline mutation is an inherited mutation that a patient is born with, and it is present in every single cell in that individual’s body. Somatic mutations, however, are not inherited and can occur throughout a person’s life. Both types of mutations can make a difference in how effective certain treatment regimens are.

For example, while an estimated 1 percent of patients with pancreatic cancer test positive for being MSI-high (MSI-H), this 1 percent of patients may be much more likely to respond to, and therefore have improved outcomes with, immunotherapy agents. Two checkpoint inhibitors Keytruda (pembrolizumab) and Opdivo (nivolumab) are approved to treat patients with colorectal cancer whose disease is MSI-H.

Perhaps similar responses can be seen in pancreatic cancer.

“Therefore, we want to make the case, based on the lethality of the disease, that we would want to test every patient with pancreatic cancer to see if they are MSI-H,” Simeone said, noting that the five-year survival rate for patients with pancreatic cancer is about 9 percent.

DNA mismatch repair deficiencies (dMMR) make up a much larger portion of patients with pancreatic cancer — about 20 percent — pointing toward the importance of getting tested.

Previously, health care teams tended to rely on family history, asking their patients if anyone in their family had pancreatic cancer or related cancers, but Simeone said that germline testing would be a much better approach, especially since so many people may not know their complete family history.

“In addition to that, we find that when we have done germline analyses of patients with sporadic pancreatic cancer without a family history, we have had about 10 to 12 percent of patients who actually have a germline mutation,” she said.

When sporadically testing patients with pancreatic cancer, Simeone said that she even discovered that one patient had a mutation in the p16 gene, which is associated with melanoma. The patient had no family history of melanoma.

“What it leads us to realize is that we’re just at the tip of the iceberg in realizing that, in some families who have these mutations, the tumors that evolve aren’t always what you think,” she said.

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