Abstract
Joy Larsen Haidle
Awareness of pancreatic cancer has grown as celebrities such as Alex Trebek share their stories, providing an opportunity to educate patients, their families and their doctors about the growing importance of the cancer's genetic connection. Recent data has led to new recommendations regarding who should consider genetic testing and cancer risk assessment, which may guide treatment and provide valuable information regarding their relatives' risk for pancreatic and other cancers.
Updated National Comprehensive Cancer Network (NCCN) guidelines now advocate that all people with pancreatic cancer consider genetic testing, as up to 20% will have an underlying inherited risk factor and up to 25% will have an identifiable mutation in the pancreatic tumor that may be useful in guiding treatment decisions.1–3 This is an important change, as previous criteria suggested that only certain people with pancreatic cancer consider testing: those who develop cancer at a young age, have multiple primary tumors or have a strong family history of cancer.
We still have work to do to share the new recommendations with the provider community and the public to ensure that those who might benefit are identified and offered access to genetic testing and genetic counseling. All patients with pancreatic cancer would benefit from a formal risk assessment and consultation with a genetic counselor to review the family history and ensure the correct genes are included on the test. It is often easy to spot a risk for inherited pancreatic cancer when there are multiple family members who had been diagnosed with the same cancer. However, some cancer patterns in a family history may be more subtle and challenging to recognize, such as combinations of breast, ovarian, prostate and colon cancers, melanoma and pancreatitis. Family structure (size and male- to-female ratio) may also influence the ease of recognizing an inherited risk factor. Genetic counselors work closely with physician colleagues and can be resources for helping guide patients and their family members through this complex process
Most attention has been given to the BRCA1 and BRCA2 genes, but there are other genes associated with an inherited predisposition to pancreatic cancer, including PALB2, ATM, CDKN2A, STK11 and Lynch syndrome. Some genes, such as PRSS1, are associated with an increased risk of developing pancreatitis and the resulting long-term inflammation can contribute to pancreatic cancer risk. In some cases, individuals with pancreatic cancer who have an inherited risk factor may benefit from additional treatment options such as platinum-based chemotherapy and/or PARP inhibitors to help target a weakness in the tumor and improve survival or extended quality time.2,4,5
Depending on the gene involved, family members may have a risk of developing other types of cancer beyond pancreatic cancer. For example, women in the family may have an increased risk of developing breast and/or ovarian cancer whereas men may have an increased risk of developing breast and/or prostate cancer.2,5 In some cases, both genders have an increased risk of developing colon cancer, melanoma or pancreatitis. Once a mutation is identified in the family, it is easier and less expensive to test other family members (referred to as familial cascade testing), and offers important information to guide heightened surveillance and risk-reduction options. The recent NCCN and Cancer of the Pancreas Screening (CAPS) consortium guidelines also offer considerations for pancreatic cancer surveillance for individuals who have a mutation in certain genes (BRCA1, BRCA2, PALB2, etc.) and a close relative with pancreatic cancer.1,6 Recent data have also focused on the behavior of cancers as a predictor for the likelihood of identifying an inherited risk, such as HER2- metastatic breast cancer in women or metastatic prostate cancer in men.2 People who fall in these categories also are candidates for pursuing genetic testing regardless of their age at the time of diagnosis or their family history. As the data unfold, genetic testing, risk assessment and genetic counseling are increasingly important for prevention, early detection and treatment planning.
Shidlovski / iStock / Getty Images Plus
In addition to treatment decisions, cancer patients are often concerned about potential cancer risks among their relatives. Often the most appropriate person in the family to test to address this concern is the person with pancreatic cancer. While it may seem counterintuitive to test the person who is known to have cancer, genetic testing works best if the ideal candidate is tested first. This guides us in determining if the test may help identify an inherited risk factor. If the test identifies a mutation, then testing is valuable for the other family members to determine if they also inherited the risk factor. However, if a mutation is not identified in the pancreatic cancer patient, then testing other family members is likely of limited utility. Although a negative test result in a relative does not confirm others in the family are not at increased cancer risk, it simply means the test did not answer the question and the result should not be used to suggest a relative does not have an increased cancer risk. In those cases, the risk assessment for relatives should be based on the cancers and ages of onset present in the family history and DNA banking for the person with pancreatic cancer would be useful to consider.
Testing individuals with pancreatic cancer offers important information for healthy relatives regarding their potential lifetime chance of developing cancer, the type of cancer, potential surveillance and risk-reduction options in addition to providing information about the benefit of genetic testing. A genetic counselor can help patients and family members understand what a genetic test does and does not tell them, as well as how they can work with their doctors to use the results to guide their medical decisions.
While adding a potential genetic connection of pancreatic cancer into patient care may seem daunting for providers, the concepts are very similar to those that have been used for years for hereditary breast and ovarian cancer or hereditary colon cancer.7 The testing options are expanding rapidly and not all tests are created equal. The triage and management options also are changing rapidly with evolving data. These trends suggest building a stronger partnership between providers and genetic counselors would improve patient care. We strongly encourage physicians to refer their patients with pancreatic cancer to genetic counselors who can partner with them to navigate the ever-changing landscape of genetic testing and help patients understand which tests may be right for them in the context of their personal and family history of cancer.
All patients with pancreatic cancer and their family members can benefit from meeting with a genetic counselor. A genetic counselor can work with people who are considering testing as well as those who have been tested to review the family history, complete a risk assessment and recommend appropriate genetic testing. Genetic counselors use several different service delivery models and may provide consultations either in-person or by telephone, which can improve access to genetic counselors even in rural or under-served areas. Patients can be referred to a genetic counselor by a healthcare provider or they may contact a genetic counselor directly, using the National Society of Genetic Counselor's (NSGC) Find a Genetic Counselor tool.
Milena Shehovtsova / iStock / Getty Images Plus
