Elena M. Stoffel, MD
The recently released ASCO Clinical Practice Provisional Clinical Opinion on Evaluating Susceptibility to Pancreatic Cancer highlights the importance of emerging data indicating a relatively high rate of germline mutations in pancreatic cancer.1 Recent studies have demonstrated that up to 1 in 10 people with pancreatic cancer carry genetic alterations specific with cancer predisposition, a higher rate than previously assumed.
Expert Panel Co-Chair Elena M. Stoffel, MD, of the University of Michigan, said that for 10% of patients with pancreatic cancer, there is a genetic factor associated with risk not only for pancreatic cancer, but for other cancer types as well. “The finding that genetic predisposition syndromes are much more common than previously expected in pancreatic cancer led [the Expert Panel] to recommend genetic testing for all individuals with pancreatic cancer,” Dr. Stoffel said.
Physicians should ask patients with pancreatic cancer to consider having germline testing done….— Alok A. Khorana, MD
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Alok A. Khorana, MD, of the Cleveland Clinic and Expert Panel Co-Chair, said that new reports during the past few years have shown that the risk of hereditary pancreatic cancer is not as low as previously thought. In some reports, it is as high as 17% or 18%, and in other reports it is approximately 4% or 5%. “The truth is probably somewhere in the middle, but it is certainly higher than the 1% we originally thought,” commented Dr. Khorana.
Another surprising finding from recent studies is that half of patients who have germline susceptibility would not have met genetic testing criteria otherwise. “If you looked at their family history, you would not have suspected they had a germline variant in genes associated with pancreatic cancer,” Dr. Stoffel said.
Germline Testing a Priority
The Provisional Clinical Opinion recommends germline testing for all patients with pancreatic cancer and assessing the risk for hereditary syndromes known to be associated with an increased risk for pancreatic adenocarcinoma. Additionally, it recommends a comprehensive review of a person’s family history of cancer. Those with a family history of pancreatic cancer affecting two first-degree relatives meet the criteria for familial pancreatic cancer. Individuals who have a family history, those with three or more diagnoses of pancreatic cancer on the same side of the family, and people who meet the criteria for other genetic syndromes associated with an increased risk for pancreatic cancer are candidates for germline testing.
“At this point, we don’t have sufficient data to demonstrate whether it is worth it to have genetic testing in a situation where an individual has only one relative with pancreatic cancer,” Dr. Stoffel said.
The Expert Panel believes there is significant clinical experience to suggest that pancreatic cancer screening “is worth discussing with certain groups of high-risk individuals,” stated Dr. Stoffel. “There have been reports of cancers diagnosed early, and certainly for families where the risk seems to be exceedingly high, screening does appear to offer some benefit. We do, however, need larger studies to demonstrate that observation.”
The Provisional Clinical Opinion notes that many of the germline mutations associated with an increased risk of pancreatic cancer are also associated with an increased risk of breast and colorectal cancers. The most common germline findings in patients with pancreatic cancer are pathogenic variants in BRCA1 and BRCA2, now associated with an estimated 3% and 5% lifetime risk for pancreatic cancer, respectively. CDKN2A germline variants are associated with an increased risk of pancreatic cancer, as are germline variants in STK11, which are associated with Peutz-Jeghers syndrome.
“Physicians should ask patients with pancreatic cancer to consider having germline testing done, because it could alter their own prognosis and choices for treatment, as well as the prognosis and treatment choices of their family members,” Dr. Khorana said. The Expert Panel recommends that this germline testing be performed early in the disease course.
“We should talk to patients with pancreatic cancer about genetics and about the possibility of a genetic diagnosis,” Dr. Stoffel said. “There should definitely be shared decision-making with patients; some patients may not want to undergo genetic testing.”
Although cost was previously a factor in decision-making about genetic testing, the expense has decreased dramatically in recent years with the proliferation of next-generation sequencing. “There are many more applications than there were previously, and there are more companies offering a lot more panels,” added Dr. Khorana.
Even with these cost reductions, the expense can still present a barrier to access for many patients. According to the Provisional Clinical Opinion, “a transparent discussion about potential out-of-pocket costs of genetic testing, as well as surveillance imaging, should be conducted with patients and families.”
Whether a genetic test result will affect a patient’s treatment for pancreatic cancer remains a difficult question to answer. Clinical trials are underway to look at specific medications for treatment of pancreatic cancer, such as immune checkpoint inhibitors and poly (ADP-ribose) polymerase inhibitors. “At this point, there are not sufficient data to say that the results of genetic tests will affect the immediate cancer treatment for the patient in front of you,” Dr. Stoffel said. “Those of us in the field think that is where we are going, but right now, it is a bit of a stretch to say that this will impact the treatment of a patient’s current pancreatic cancer. However, this is an opportunity to identify families at high risk and to explain that the benefit of genetic testing could be extended to family members.”
This type of testing expands the circle of people who could benefit, noted Dr. Khorana. Pancreatic cancer is difficult to treat because it is often diagnosed late, after it has advanced. “It makes sense to try to find it sooner in potentially affected family members, as you could intervene sooner and potentially offer them better options,” Dr. Khorana said. ■
DISCLOSURE: For full disclosures of the ASCO Expert Panel members, visit www.jco.ascopubs.org.
1. Stoffel EM, McKernin SE, Brand R, et al: Evaluating susceptibility to pancreatic cancer: ASCO Provisional Clinical Opinion. J Clin Oncol 37:153-164, 2019.
Originally published in ASCO Daily News. © American Society of Clinical Oncology. ASCO Daily News, December 21, 2018. All rights reserved.