Conference Coverage

BRCA2 mutations linked to greater risk for pancreatic cancer


MIAMI BEACH – Although population-wide screening for pancreatic cancer is considered unfeasible and costly, new evidence suggests a benefit to screening a select population: people who test positive for BRCA2 genetic mutations.

Cross-sectional imaging of 117 people with BRCA2 mutations revealed pancreatic abnormalities in 10 patients, including a patient with pancreatic cancer whose only symptom was unexplained weight loss.

Pancreatic cancer is not as common as are some other malignancies, with an incidence estimated between 1% and 3%. However, it is a particularly deadly form of cancer, with only 7.7% of people living to 5 years after diagnosis, according to data from the National Cancer Institute.

A relatively low incidence is a good thing, but it also limits widespread screening. “There is a low predictive value of screening the population at large, and it is not considered cost effective,” said Eugene P. Ceppa, MD, a general surgeon at IU Health University Hospital, Indianapolis. However, patients at high risk for pancreatic adenocarcinoma might be worth targeting for screening, he added.

Dr. Eugene P. Ceppa

Dr. Eugene P. Ceppa

Emerging research indicates BRCA2 mutation status is associated with higher risk. For example, a study of 1,072 people with deleterious BRCA mutations revealed a statistically greater number of observed pancreatic cancer cases, versus what would be expected among those with BRCA2 abnormalities (standardized incidence ratio of 21.7, P less than .001; Cancer. 2015 Jan 15;121:269-75).

“This represents a 21% increase in the chance of pancreatic cancer in these patients,” Dr. Ceppa said.

Buoyed by these and other findings, Dr. Ceppa and his colleagues launched a study of their own. “Our hypothesis is that screening all BRCA2s would identify more patients with pancreatic cancer,” he said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

Dr. Ceppa and coinvestigators reviewed electronic medical records at their institution from 2005 to 2015. They identified 204 BRCA mutation carriers, and after excluding 87 BRCA1 positive patients, further assessed the 117 with documented BRCA2 mutations. A total 47 people (40%) of this group had undergone cross-sectional imaging. The images were initially reviewed, and then re-reviewed for the study, by radiologists with specific expertise in pancreatology.

The cross-sectional imaging revealed pancreatic abnormalities in 10 people, including 1 patient with a pancreatic ductal adenocarcinoma located in the head of the pancreas. Another nine patients had intraductal papillary mucinous neoplasms (IPMNs). There were no significant demographic or clinical differences between the groups of patients with and without the imaging abnormalities, Dr. Ceppa said.

The investigators also compared the patients with BRCA2 mutations against a historical cohort representing the general population. They found 21% of patients with BRCA2 had a defined pancreatic abnormality, compared with 8% in the general population. The difference was statistically significant (P = .007).

Interestingly, the same comparison also revealed a rate of IPMN of 19%, versus 1%, respectively (P less than .001). “BRCA2 mutation carriers have significantly higher incidence of IPMN than the general population,” Dr. Ceppa said.

The study results support a high-risk screening protocol in asymptomatic BRCA patients regardless of family history, he said. In fact, a high-risk screening protocol implemented at his institution in 2013 led to a 14% detection rate of pancreatic cancer among BRCA2-positive patients, compared with a 3% rate in the general population.

“Your most significant finding might be the more IPMN patients – but how do we follow them, and will it be cost effective?” asked invited discussant Matthew J. Weiss, MD, of Johns Hopkins Medicine in Baltimore.

One of the most notable impacts of instituting the high-risk screening protocol has been an increase in patient referrals from other specialists at Dr. Ceppa’s institution. “I’ve looked at every single breast surgeon in our department, and I know how each of them are referring,” he explained.

Following initial screening of BRCA2 mutation patients, Dr. Ceppa repeats screening at 6 months, 1 year, and then annually. “However, some insurers may balk at our recommendations for frequency of screening,” he noted.

Dr. Ceppa and Dr. Weiss had no relevant financial disclosures.

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