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BRCA1/2 Mutations in Patients with Pancreatic Cancer: Do Certain Characteristics Predict Carriers?

Jun 15, 2015

A recent study in the Journal of Clinical Oncology (JCO) sought to determine the percentage of patients with pancreatic ductal adenocarcinoma (PDAC) who carry pathogenic BRCA1 and BRCA2 mutations. The study, “Germline BRCA Mutations in a Large Clinic-Based Cohort of Patients With Pancreatic Adenocarcinoma,” also set out to assess whether patients who do carry the genes are more likely to have certain clinical and family history characteristics; knowing which factors predict the presence of mutations allow doctors to identify patients—and patients' family members—who would most likely benefit from genetic testing and counseling.  

The study, published online, ahead of print, May 4, analyzed the medical records, family history, and DNA of 306 patients with PDAC who were being treated at the Princess Margaret Cancer Centre at the University Health Network, a large academic medical center in Toronto. The study found that 14 out of the 306 patients, or 4.6 percent, carried pathogenic germline BRCA mutations; eleven patients carried BRCA2 mutations and three patients carried BRCA1 mutations.

Study coauthor Steven Gallinger, MD, MSc, FRCSC, explained the importance of knowing the extent of BRCA1/2 mutations among patients with PDAC.

“First, understanding the prevalence helps raise awareness among practicing oncologists that there is an association between carrying a BRCA1/2 mutation and increased risk for pancreatic cancer. Second, what the research is suggesting now, although it is still not totally clear, is that carriers treated with PARP inhibitors or platinum-based agents may have improved survival. This is an interesting new topic that is well-known in breast and ovarian cancer but not as well-appreciated in pancreatic cancer.”

Patient and family characteristics do not predict BRCA mutations among patients with PDAC

Upon looking at the specific clinical or family characteristics of the 14 patients who were BRCA1/2-positive, the researchers found that those patients were no more likely than patients without BRCA mutations to have a personal history of breast or ovarian cancer or a first, second, or third degree relative with breast or ovarian cancer. Having a BRCA1/2 mutation was associated with being of Ashkenazi Jewish descent and having a cancer family history that met genetic testing criteria of the National Comprehensive Cancer Network or the Ontario Ministry of Health. However, the majority of carriers did not meet these genetic testing criteria.

Commenting on these findings, Dr. Gallinger said, “Half of the cases that we found to be positive for BRCA1/2 mutations did not have a strong family history of breast or ovarian cancer, so if you’re deciding who to test for mutations based on family history, you’re going to miss a lot of people who are carriers.”

Based on the results of the study, the authors wrote in the JCO article, “. . . At this time, clinical screening for early detection of PDAC has limited effectiveness.” The authors recommend, however, that Jews of Ashkenazi descent should be tested since these patients are more likely to carry mutations, independent of medical or family history of cancer.

Sampling a large, representative population

According to Dr. Gallinger, among studies aimed at determining prevalence of BRCA1/2 in patients with PDAC, this is the first to look at a consecutive series of clinic-based unselected cases. That is, previous studies focused on populations known to have a higher percentage of carriers, such as Ashkenazi Jews, while in the current study, researchers approached all patients who came to Princess Margaret for PDAC treatment. Since focusing on high-risk populations might skew the data towards a higher prevalence, Dr. Gallinger thinks the lower rate of 4.6% found in this “non-select” study might more accurately capture the real prevalence in the population of patients with PDAC. Princess Margaret sees approximately 25 percent of all new PDAC cases in the province of Ontario.

“We tried to approach everybody who came in the door,” said Dr. Gallinger. “Of course, there are some natural biases with people coming in our door, because they may be different from people who don’t come to our Centre. But we understand our population and think it does very much represent the real world.”

Steven Gallinger, MD, MSc, FRCSC, is a clinician-scientist and surgical oncologist at the Princess Margaret Cancer Centre of the University Health Network.


Abstract of the original JCO article.

PDF of the original JCO article.


Holter S, Borgida A, Dodd A, et al. Germline BRCA mutations in a large clinic-based cohort of patients with pancreatic adenocarcinoma.  J Clin Oncol. Epub 2015 May 4.


The Exclusive Coverage series on ASCO.org highlights selected research from JCO and JOP with additional perspective provided by the lead or corresponding author.

@ 2014 American Society of Clinical Oncology

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