Genetic Tests: NCCN Updates Genetic Breast, Ovarian & Pancreatic Testing Guidelines

On Dec. 4, the National Comprehensive Cancer Network (NCCN) issued updated guidelines for use of genetic testing to assess the risk of breast, ovarian and pancreatic cancer. The headliners of the new guidance include a new approach and organization that goes beyond BRCA mutations, broadening of existing pancreatic, breast and ovarian testing recommendations and continued skepticism about direct-to-consumer genetic testing. Here is a rundown of all the key points. Changes in Approach The NCCN has been issuing genetic testing guidelines since the BRCA genes were discovered two decades ago. Key structural changes in the revised guidelines include:

• Inclusion of information about new genes discovered after BRCA, including with regard to breast, ovarian and pancreatic cancer risk;
• Reorganization of the guidelines by disease and syndrome type; and
• Streamlined information about subsequent steps for people who meet genetic testing criteria.

Broader Criteria for Pancreatic Cancer Testing The NCCN continues to recommend genetic testing for all pancreatic cancer patients but now has a greater recognition of the genetic risks associated with pancreatic cancer. Accordingly, the new testing guidelines are broader and include more information on the screening or management approaches clinicians should take with individuals who have pathogenic or likely pathogenic mutations in genes associated with pancreatic cancer, including not just BRCA1/2 but also other inherited gene mutations that studies have linked with high risk of pancreatic cancer, including:

• ATM;
• CDKN2A;
• MSH2;
• MLH1;
• MSH6;
• EPCAM;
• PALB2;
• STK11; and
• TP53.

  “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),” noted NCCN guideline panelist Matthew B. Yurgelun, MD., of the Dana-Farber Cancer Institute in Boston. Broader Criteria for Cancer Testing of Ashkenazi Individuals The NCCN also maintains its longstanding recommendation of genetic testing for individuals of Ashkenazi Jewish descent who have breast cancer or prostate cancer. But the revised guidelines broaden that recommendation to include testing for all individuals with Ashkenazi Jewish ancestry, regardless of family cancer history, within research studies for the three cancer-linked founder mutations in BRCA1/2 that show up in this population at increased rates. If they cannot participate in a research study, the guidelines say these individuals can receive commercial testing with appropriate pre- and post-test counseling and follow-up management. “Testing should not be offered outside of a medical framework or clinical trial,” the NCCN cautions. Continued Wariness Over DTC Testing To the disappointment of consumer genetic testing laboratories, the NCCN experts who created the revised guidelines continued to throw cold water on direct-to-consumer genetic testing, stressing its limitations and the potential need for confirmatory testing. “More and more patients are presenting to clinic[s] having already had themselves tested through direct-to-consumer labs,” Robert Pilarski from the Ohio State University Comprehensive Cancer Center and vice-chair of the guidelines panel noted in a statement. “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.”