BRCA2‐associated pancreatic cancer and current screening guidelines (2015)

As is previously known, germline mutations have been identified in a few known cancer genes, such as BRCA2, that predispose individuals to developing pancreatic adenocarcinoma.1 Based on advancements made in the understanding of the function of these genetic alterations, the identification of these mutations not only has clinical implications for the individual patient but also for their family. Identification of carrier status has led to the development of very clear guidelines for screening and/or management with respect to breast cancer and ovarian cancer. However, to the best of our knowledge, a clear-cut consensus has not been reached with regard to screening high-risk individuals for pancreatic adenocarcinoma. We know from prior studies that BRCA2 carriers are at a higher risk of developing pancreatic cancer.2 However, the standard incidence ratios (SIRs) quoted by Mersch et al for pancreatic cancer when compared with breast, ovarian, prostate, and other cancer subtypes are striking and a cause for concern (males: SIR, 82.559; 95% confidence interval, 39.524-151.84 [P < .001]; females: SIR, 13.809; 95% confidence interval, 6.301-26.216 [P < .001]).3 Despite recent therapeutic advances for pancreatic cancer and potential individualized therapy for BRCA2 mutation carriers in the form of DNA-damaging agents (such as platinum compounds) or poly (ADP-ribose) polymerase (PARP) inhibitors, clinical outcomes are still dismal. There have been studies evaluating the role of endoscopic ultrasound (EUS) in high-risk individuals leading to the identification of both malignant and premalignant lesions.4 The majority of the studies that defined “high-risk” individuals for pancreatic cancer were not limited to BRCA2, and despite the small heterogeneous groups studied, EUS did lead to the identification of clinically significant pancreatic lesions in a sizeable percentage (up to 42%) of asymptomatic individuals.5-7 Based on the accumulating data and the relative safety and feasibility of EUS, especially in tertiary care centers, germline BRCA2 mutation carriers represent a high-risk subset of patients who would potentially benefit from more intense surveillance in the form of EUS and/or other surveillance methods (eg, magnetic resonance cholangiopancreatography), as noted by a majority of the 49-expert multidisciplinary international consortium (International Cancer of the Pancreas Screening [CAPS]).8 However, the impact of early detection on overall survival would still need to be determined. Nevertheless, these results open the debate regarding the need for aggressive surveillance in these individuals. What type of surveillance and age parameters have yet to be determined. Minimization of controllable risk factors such as smoking and obesity in at-risk patients is also likely important. Within the subset of pancreatic cancers identified in the study by Mersch et al,3 it would be important to discuss the age distribution at the time of diagnosis to help guide some of these screening guidelines. No specific funding was disclosed. The authors made no disclosures. Pashtoon Murtaza Kasi, MD Katrina S. Pedersen, MD Robert R. McWilliams, MD Division of Medical Oncology Mayo Clinic Rochester, Minnesota