Elena M. Stoffel, MD, MPH
In a provisional clinical opinion (PCO), an expert panel convened by the American Society of Clinical Oncology (ASCO) has recommended that patients with pancreatic cancer undergo assessment of risk for hereditary syndromes that contribute to higher likelihood of pancreatic cancer. The PCO also defines criteria for those with a familial history of pancreatic cancer who should receive testing.1
The PCO notes that recent evidence suggests that up to 10% of patients with pancreatic cancer have germline mutations that predispose them to cancers, adding that “pathogenic germline variants in specific genes have been associated with lifetime risks of pancreatic cancer ranging from 4% to 40%.” Common mutations in pancreatic cancer include BRCA1
, for which patients are screened in the setting of breast and ovarian cancers.
“The prevalence of genetic predisposition among patients with pancreatic cancer was much higher than we had originally anticipated, lead author Elena M. Stoffel, MD, MPH, said in an ASCO podcast about the PCO.2
“This is relevant because in talking about pancreatic cancer as one of the deadliest cancers in the United States and worldwide, we are very interested in finding ways to reduce the morbidity from this cancer to patients and their families.”
The PCO recommends use of a multigene panel that tests for germline variants known to be associated with increased risk for pancreatic cancer, including BRCA1/2
, Lynch syndrome mutations, PALB2
, and STK11
, which is associated with Peutz- Jeghers syndrome (Table 1
The PCO does not carry the weight of a guideline change because the body of evidence is not strong enough, but the evidence trends in support of recommendations for germline and familial history pancreatic cancer testing do warrant issuance of the opinion at this time, said Stoffel, assistant professor of internal medicine and director of the Cancer Genetics Clinic at the University of Michigan in Ann Arbor. Stoffel is a member of the ASCO Committee for Cancer Genetics.Recommendation for Comprehensive Review
The PCO recommends that a comprehensive review of family history of cancer be performed for patients with pancreatic cancer. Those with cancer affecting 2 firstdegree relatives fit the classification of having familial pancreatic cancer (FPC) under the PCO, and those with FPC and a history of 3 or more diagnoses of pancreatic cancer on the same side of the family, as well as patients identified as having genetic susceptibility for pancreatic cancer, are candidates for testing, according to the PCO. “Even if family cancer history is unremarkable,” it is appropriate to discuss genetic testing with individuals with a diagnosis of pancreatic cancer, the PCO states. The benefits and limitations of genetic testing for susceptibility should also be discussed with patients, the PCO states.
Table 1. Syndromes and Gene Mutations Associated With Pancreatic Cancer3
This approach to screening will help answer questions commonly asked by patients with pancreatic cancer about the significance their own cancer has for family members and how to prevent them from developing pancreatic cancer, Stoffel said.
Table 2. Modifiable Risk Factors Associated With Pancreatic Cancer7
“If 1 out of 10 patients with pancreatic cancer develops their cancer in the setting of a genetic predisposition syndrome, this has tremendous implications for management for them and their family members. One of the most common inherited cancer syndromes identified in families affected with pancreatic cancer is hereditary breast/ovarian cancer,” Stoffel said.Incidence of Pancreatic Cancer