NCCN Publishes Updated Genetic Risk Assessment Recommendations

December 18, 2019

The updated and expanded NCCN guidelines broaden the testing criteria, while clarifying who should be tested for genetic mutations.

New evidence-based criteria that focuses on broader testing guidelines, and an aim to simplify the format for practicing physicians were the key drivers of recent updates to the National Comprehensive Cancer Network (NCCN) Guidelines for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic.

“We had 2 main goals with this round of the guidelines,” said Mary B. Daly, PhD, FACP, of the Fox Chase Cancer Center in Philadelphia, who also serves as the chair of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic. “One, of course was to keep up to date with the evidence as it continues to emerge so that it can inform the guidelines we write. The other thing is that we tried really hard to address the problem that’s been raised that the guidelines are confusing and difficult for a physician to use.”

While these NCCN guidelines still do have some focus on BRCA1 and BRCA2 mutations, they also now include several other moderate and high penetrance genes that have been associated with breast, ovarian, and pancreatic cancers.

“There are a handful of genes that increase the risk of ovarian cancer,” said Elizabeth Etkin-Kramer, MD, FACOG, assistant professor of gynecology at Florida International University, Herbert Wertheim School of Medicine. “And if somebody has a lifetime risk of 50%, I need to know that, as there are different things that I would recommend. So, to me this is huge.”

In order to simplify the genetic testing criteria, the guidelines were reorganized by disease and syndrome type, and feature new recommendations specifically for people with Ashkenazi Jewish Ancestry who have not been diagnosed with cancer.

“In certain populations, such as Ashkenazi Jewish women and men, from family history, if we follow the old guidelines, we would miss over 50% of the BRCA carriers,” said Etkin-Kramer. “So, the beauty is the newer guidelines take that into context and say, okay, this needs to be addressed because we don't want to miss that many BRCA carriers because it's such a highly penetrant gene.”

Pancreatic cancer was also added to the title of the guideline, with a new section devoted entirely to pancreatic cancer screening and genetic testing, recommending that all patients with pancreatic cancer go through the testing process. The testing can help determine which treatment may be most effective, and also help family members make informed decisions about possible preventative action.

“There’s been an explosion of recent data showing that roughly 4-10% of individuals with pancreatic cancer harbor inherited genetic mutations, including BRCA1BRCA2ATM, the Lynch syndrome genes, and others,” said Matthew B. Yurgelun, MD, from Dana-Farber/Brigham and Women’s Cancer Center in Boston, and a member of the NCCN guidelines panel, in a press statement. “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.”

The guidelines continue to highlight the importance of genetic counseling for patients to ensure that test results, and the implications that arise from them, are fully understood. The panel also warned about the risks that come from utilizing direct-to-market services for the testing process, noting that results obtained in that way may still need to be confirmed by a secondary laboratory prior to being used in a clinical setting.