A friendly doctor holding a patient's hand sitting at her desk for encouragement, empathy and support following a medical examination.
A friendly doctor holding a patient's hand sitting at her desk for encouragement, empathy and support following a medical examination.

Updated genetic screening guidelines with practice recommendations for genetic and familial high-risk breast, ovarian and pancreatic cancers, published by the National Comprehensive Cancer Network (NCCN), feature emerging evidence on personalized medicine.

The new guidelines, created and maintained by an interdisciplinary panel of experts from NCCN leading cancer centers as well as patients and advocates, include several updates—including new and expanded sections on risk assessment and management related to three major cancer types and also maintaining a more conservative approach toward testing practices where the evidence is still lacking.

In the rapidly-moving field of cancer care and genetics, the updated NCCN Guidelines® combine the latest evidence and expert consensus. These recommendations are firmly supported by quality research and establish the best management paradigms that improve outcomes for people with cancer.

“These guidelines are as inclusive as possible, wherever there’s strong, unbiased evidence to back up our recommendations,” noted Mary B. Daly, MD, Ph.D, FACP, Fox Chase Cancer Center, Chair of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic.

“[These] guidelines include genes that have been found to increase cancer-susceptibility. These NCCN Guidelines still have a strong focus on BRCA1 and BRCA2 mutations, but also now include other high and moderate penetrance genes associated with breast, ovarian, and pancreatic cancer,” Daly said.

We continuously review any new data on genes that might increase a person’s risk of getting cancer or impact the effectiveness of their treatment,” she added.

Simple criteria
The updated guidelines are concentrated around simplified criteria to clarify the genetic testing process.

For example, in a newly-added guide for individuals of Ashkenazi Jewish ancestry who have not been diagnosed with cancer, genetic testing may be offered for the three Ashkenazi Jewish founder mutations in the context of a long-term research study, regardless of family history. These individuals should be encouraged to consult with a cancer genetics professional.

Disease and syndrome type
The updated NCCN Guidelines are organized by both disease and syndrome type, and also include a section with streamlined information on appropriate subsequent steps for persons who meet criteria for genetic testing.

The author panel recognize that genetic mutations can impact the approach to cancer treatment. As a result, the guidelines now state that testing may be clinically indicated if it will aid in systemic therapy decision-making.

“Genetic testing is becoming increasingly utilized in oncology because of its potential to impact surgical decisions and chemotherapy,” said Robert Pilarski, MS, LGC; MSW, Licensed Genetic Counselor, Professor, Clinical Internal Medicine, The Ohio State University Comprehensive Cancer Center, Vice-Chair of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic.

“At the same time, the complexity of this testing is increasing. [With a] growing number of genes and tests available, a limited understanding of the management implications of some of the newer genes, and even uncertainty over the implications of mutations in well-established genes in some situations –for example in a condition known as ‘mosaicism,’ in which the mutation is not present in all of the cells of the body. Because of this, the NCCN Guidelines continue to highlight the critical importance of genetic counseling for patients prior to undergoing genetic testing to ensure that patients are fully informed of the test implications,” Pilarski explaind.

He also offered an important word of caution about the potential risks from direct-to-consumer genetic testing, adding: “More and more patients are presenting to clinic having already had themselves tested through direct-to-consumer labs. Providers need to be aware that the tests offered by many of these labs are not equivalent to traditional genetic testing, and the results may need to be confirmed in another laboratory before being used for clinical care.”

Pancreatic cancer
The updated guidelines recommend that all pancreatic cancer patients get genetic testing. The recent update includes more information about which genes are associated with pancreatic cancer recommendations. Genetic testing in pancreatic cancer can help determine which treatments would be most effective (e.g. PARP inhibitors) and if family members would benefit from screening and preventive action.

“There’s been an explosion of recent data showing that roughly 4-10% of individuals with pancreatic cancer harbor inherited genetic mutations, including BRCA1, BRCA2, ATM, the Lynch syndrome genes, and others,” explaind Matthew B. Yurgelun, MD, Dana-Farber/Brigham and Women’s Cancer Center, Member of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic.

“Such data have, surprisingly, shown that classic ‘high-risk’ features of inherited cancer risk (e.g. young age at diagnosis, strong family histories of cancer) are often absent in individuals with pancreatic cancer who carry these mutations. Based off of these data, there is now a compelling reason for all individuals with pancreatic cancer to be offered genetic counseling and germline testing for such variants—particularly given the possibility that their at-risk family members could greatly benefit from known, effective cancer risk-reducing interventions (e.g. surgical removal of the ovaries for female BRCA1/2 mutation carriers),” Yurgelun said.

“Emerging data have also begun to suggest possible benefits to pancreatic cancer screening in select high-risk individuals who harbor such mutations. These new guidelines address many of the important nuances and limitations of this exciting and rapidly evolving body of literature,” he added.

Advocacy
“Participating on the NCCN panel allows [us] to share the real-world experiences of patients making complex, and often agonizing medical decisions about hereditary cancer treatment and risk management,” said Sue Friedman, DVM, Executive Director, Facing Our Risk of Cancer Empowered (FORCE), Member of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic.

“As an advocacy organization for people and families affected by hereditary cancer, we see the importance of having standardized guidelines. These guidelines are a critical piece of informed decision-making; we frequently direct our community to NCCN for up-to-date, clear, and credible information developed by experts in the field,” Friedman added.

In addition to covering at least 97 percent of cancers affecting patients in the United States, there are also NCCN Guidelines for detection, prevention, risk-reduction, supportive care, and guidelines for specific populations.