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Genetics & Genomics

Hereditary Pancreatic Cancer Syndromes: Providing Care to At-Risk Families

Elisabeth King
Bita M. Nehoray
CJON 2019, 23(6), 579-582 DOI: 10.1188/19.CJON.579-582

Hereditary pancreatic cancer continues to pose challenges to providers, as well as to patients and their families. Pancreatic cancer has a poor prognosis, and individuals with family histories of pancreatic cancer are often motivated to pursue genetic testing. This article reviews various hereditary pancreatic cancer syndromes, as well as pancreatic cancer screening recommendations, options, and limitations.

AT A GLANCE

  • Individuals at risk of hereditary pancreatic cancer should be referred to a genetics professional for formal genetic cancer risk assessment and genetic testing, when appropriate.
  • Nurses should understand the cancer risks associated with various hereditary pancreatic cancer syndromes, inform patients that recommendations are continually evolving, and provide patient support to ensure that cancer prevention and early detection recommendations are implemented.
  • Individuals and family members at increased risk of pancreatic cancer should be encouraged to adopt positive health behaviors and find ways to cope with emotional distress and adapt.

The American Cancer Society ([ACS], 2019) estimates that 56,770 new cases of pancreatic cancer will be diagnosed in the United States in 2019. Pancreatic cancer accounts for 3% of all cancers and 7% of all cancer deaths (ACS, 2019). Most pancreatic cancers are adenocarcinomas.

Symptoms of pancreatic cancer can include jaundice, abdominal or back pain, anorexia and weight loss, nausea, and vomiting (ACS, 2019). Blood clots, diabetes, or gallbladder or liver enlargement might also suggest pancreatic cancer. Because of the location of the pancreas within the body, pancreatic cancer is notoriously difficult to detect at earlier stages. Often by the time that a patient is symptomatic, his or her cancer has progressed to a more advanced stage. Individuals diagnosed with pancreatic cancer often have a poor prognosis, which is linked to the challenges associated with early detection; the five-year survival rate among those diagnosed with any stage of pancreatic cancer is just 9% (ACS, 2019).

The primary modifiable risk factors for pancreatic cancer include using tobacco and being overweight (ACS, 2019). Others include alcohol abuse and diets high in sugar and meat (Midha, Chawla, & Garg, 2016), as well as increasing age, gender (more common in men), race (more common in African Americans), diabetes, chronic pancreatitis, family history, and inherited genetic syndromes (Midha et al., 2016).

Hereditary Pancreatic Cancer Syndromes

Cancers are generally caused by acquired gene mutations that occur over time because of various exposures or random events, and pancreatic cancer is no different. However, some individuals inherit gene mutations that increase their risk of pancreatic or other cancers. About 10% of all individuals diagnosed with pancreatic cancer have a first- or second-degree relative with pancreatic cancer, suggesting an inherited risk (Syngal et al., 2015).

The most common gene mutations found in familial pancreatic cancer testing are in the BRCA1, BRCA2, CDKN2A, PALB2, and ATM genes (Syngal et al., 2015). Mutations in these genes have also been associated with other types of cancer, such as breast cancer, prostate cancer, and melanoma (see Table 1). Of the more commonly identified familial pancreatic cancer gene mutations, CDKN2A confers the highest lifetime risk of pancreatic cancer, and individuals with a CDKN2A mutation have as much as a 39-fold increased risk of developing pancreatic cancer within their lifetime (Syngal et al., 2015). Although relatively uncommon, STK11 mutations confer the highest known risk of pancreatic cancer (132-fold) (Syngal et al., 2015). Mutations in STK11 cause a condition called Peutz–Jeghers syndrome in which patients develop gastrointestinal polyps and are at risk for various cancers.

Familial pancreatic cancer has been defined as a family having at least two first-degree relatives with pancreatic cancer (Syngal et al., 2015). Identifiable genetic mutations are found in only 20% of families with familial pancreatic cancer, so the causes of most instances of familial pancreatic cancer remain unknown (Syngal et al., 2015). Research is ongoing to better understand potential sources of genetic risk, but it is thought that the elevated risk may be attributable to a combination of one or more genes, as well as possible environmental factors.

Given that most individuals diagnosed with pancreatic cancer will present with late-stage disease, identifying individuals who may have an elevated risk is crucial. National Comprehensive Cancer Network ([NCCN], 2019a) guidelines recommend germline BRCA1 and BRCA2 testing for all individuals with a personal history of pancreatic cancer and for individuals who have a first- or second-degree relative with pancreatic cancer. Studies assessing the spectrum of actionable variants in hereditary pancreatic cancer support the consideration of a multigene panel testing approach (Hu et al., 2018; Slavin et al., 2018); many families meet the criteria for more than one hereditary cancer syndrome. Pragmatic considerations for multigene panel testing may include uncertainty regarding reimbursement for repeated germline testing and the inability to test an affected individual in the future because pancreatic cancer is a highly lethal disease.

Pancreatic Cancer Screening

The International Cancer of the Pancreas Screening Consortium provides the most recognized consensus guidelines on who should be screened for pancreatic cancer (Goggins et al., 2019). Individuals with increased risk of pancreatic cancer should undergo baseline studies, including magnetic resonance imaging (MRI)/magnetic resonance cholangiopancreatography (MRCP) with contrast, endoscopic ultrasonography (EUS), and fasting blood glucose and/or hemoglobin A1c (HbA1c) (Goggins et al., 2019). If there are no abnormalities, screening should continue annually with routine fasting blood glucose and/or HbA1c and alternating MRI/MRCP and EUS (Goggins et al., 2019). Recommendations regarding age to initiate screening vary based on gene mutation status and family history (Goggins et al., 2019) (see Table 2). The International Cancer of the Pancreas Screening Consortium recommends that only individuals who would be candidates for surgery if a lesion was found should undergo screening, so health status should always be considered prior to discussions regarding screening (Goggins et al., 2019).

A successful screening protocol for pancreatic cancer is one that is able to detect high-grade precursors because even stage IA pancreatic cancers have a low survival rate. In a study of 139 asymptomatic adults at high risk of pancreatic cancer undergoing first-time screening, two solid lesions and nine cysts were detected in nine individuals (Harinck et al., 2016). Both solid lesions were detected by EUS only; of the cysts, six were detected by EUS and MRI, and three were detected by MRI only (Harinck et al., 2016). Harinck et al. (2016) also found that EUS is more sensitive for the detection of solid lesions, whereas MRI/MRCP is more sensitive for the detection of cystic lesions, further demonstrating that the two modalities are complementary and not interchangeable. A systematic review of pancreatic cancer screening in high-risk individuals by Lu et al. (2015) revealed that EUS was the primary means of detection in pancreatic cancer screening studies, diagnosing 64.3% of pancreatic cancers, whereas endoscopic retrograde cannulation of the pancreas, MRI, and CT diagnosed 28.6%, 42.9%, and 21.4% of pancreatic cancers, respectively.

EUS involves endoscopy with high-frequency ultrasound and allows for the detection, staging, and tissue sampling of pancreatic neoplasms. It requires sedation and can take about 30–90 minutes. Risks include bleeding, infection, perforation, and pancreatitis. Although the ability of EUS to detect small lesions (less than 1 cm) is appealing, it is a high-cost imaging technique that is operator dependent and has high interobserver variability.

MRI/MRCP offers a noninvasive method of screening that includes complete abdominal imaging of the abdomen and pelvis and can detect extrapancreatic neoplasms. Unlike EUS, MRI/MRCP does not allow tissue to be sampled during the procedure. Average procedure time is about 20 minutes, and potential risks include allergic reaction to the contrast injection and renal toxicity because the contrast injection contains gadolinium. Individuals with implanted metal cannot be screened with MRI/MRCP.

Patients may inquire about tumor biomarkers as a screening modality for pancreatic cancer. CA 19-9 is the most commonly used biomarker; however, it should not be used as a screening tool for pancreatic cancer because of its low sensitivity and specificity (Poruk, Firpo, Adler, & Mulvihill, 2013). Its primary use is monitoring treatment response, but it may also be used as part of a workup for abnormal pancreatic imaging (Goggins et al., 2019).

Because research has not determined the best screening modality, individuals are encouraged to undergo screening at facilities with expertise in and protocols for pancreatic screening. In addition, screening patients based on study protocols provides data that will establish effective screening modalities and evidence-based screening guidelines (Goggins et al., 2019).

Conclusion

The limitations of screening, coupled with the high morbidity and mortality of a pancreatic cancer diagnosis, pose challenges when counseling individuals at elevated risk of the disease. Nurses must acknowledge that such a diagnosis can be overwhelming and frightening, and they must also identify families who might benefit from germline genetic testing and refer them to a genetics professional. Although discussing the limitations of screening is important, individuals may be reassured to hear that most with a hereditary pancreatic cancer syndrome will not develop pancreatic cancer. Patients and families need reassurance that research is continuing on how to best screen for pancreatic cancer. Modifiable risk factors for pancreatic cancer should be discussed because most of these are within the individual’s control. Time should be devoted to promoting positive health behaviors as a means to reduce risk and optimize health. Hereditary pancreatic cancer poses challenges to providers, patients, and families. Nurses are well-equipped to identify, educate, and support individuals who have an elevated risk of pancreatic cancer.

About the Author(s)

Elisabeth King, MSN, RN, FNP, AOCNP®, AGN, is the senior manager of cancer risk counseling and Bita M. Nehoray, MS, LCGC, is a genetic counselor, both at City of Hope in Duarte, CA. The authors take full responsibility for this content. Nehoray serves on the Invitae Genetic Counseling Advisory Board. King can be reached at eking@coh.org, with copy to CJONEditor@ons.org.

 

References 

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