BRCA1/2 Gene Mutations Observed in Pancreatic Cancer

Testing for BRCA gene mutations has become a mainstay for patients with breast cancer and their first-degree relatives. There may also be a connection between BRCA mutation carriers and those with pancreatic cancer. 

A small study was conducted in Italy to learn more about this relationship.  A clinical database review from two Genetic Oncology Services in northern Italy identified 25 Italian families with a patient with pancreatic cancer who had at least one first-degree relative with BRCA-associated breast and/or ovarian cancer.

The study concluded that BRCA1 and BRCA2 mutations are observed with nearly equal distribution in breast and/or ovarian cancer relatives of patients with either familial pancreatic cancer or sporadic pancreatic cancer.¹ More studies will further elucidate the relationship between family history, BRCA mutations, and pancreatic cancer in families with hereditary cancer syndrome, and this is an important finding.

Additionally, a recent editorial in the Journal of Clinical Oncology addressed the significance of these mutations in patients with pancreatic cancer. Carnevale and Ashworth² state that pancreatic ductal adenocarcinoma (PDAC) remains one of the greatest challenges in oncology because the median survival remains less than 1 year for advanced stages, and for early-stage resectable disease, 5-year survival is only around 25%.³  Although the lifetime risk of being diagnosed with PDAC is very low (around 1.5%),³ approximately 10% of people who are diagnosed with PDAC are estimated to have a hereditary predisposition based on a germline BRCA mutation. 

Finding the most appropriate treatment regimen remains somewhat elusive. “Some retrospective reviews have suggested that platinum-based regimens (with particular emphasis on cisplatin which is not commonly used in patients with PDAC) increase overall survival in patients with BRCA-mutant PDAC; however, there have not yet been high-quality prospective trials to confirm or quantify this benefit,” the authors said.^{4, 5}

Because pancreatic cancer is difficult to diagnose at early stages and less likely to lead to overall survival for many, this study and editorial underscore the need for more research and clinical trials. Carnevale and Ashworth recommend screening patients with PDAC for germline BRCA1/2 mutations in hopes that it would boost clinical trial enrollment for this disease.

References:

• Boggiani D, Bella M, Zanelli P, et al. (2015). Family history for BRCA1 and BRCA2 mutations in patients with pancreatic cancer: An observational, population-based study. American Society of Clinical Oncology Meeting Abstracts.
• Carnevale J, Ashworth A. (2015). Assessing the Significance of BRCA1 and BRCA2 Mutations in Pancreatic Cancer.  Journal of Clinical Oncology.
• The Surveillance, Epidemiology, and End Results (SEER) Program. (2014). SEER Cancer Statistics Review, 1975-2011. National Cancer Institute.
• Golan T, Kanji ZS, Epelbaum R, et al. (2014). Overall survival and clinical characteristics of pancreatic cancer in BRCA mutation carriers. British Journal of Cancer, Sep 9; 111(6):1132-8.
• Lowery MA, Kelsen DP, Stadler ZK, et al. (2011). An emerging entity: pancreatic adenocarcinoma associated with a known BRCA mutation: clinical descriptors, treatment implications, and future directions. Oncologist, 16(10):1397-402.