NCCN Expands Genetic Risk Assessment Guidelines to Include Additional Tumor Types

National Comprehensive Cancer Network updated 2 guideline resources to keep providers and other stakeholders up to date on cutting-edge genetic research.

The NCCN has expanded its Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Genetic/Familial High-Risk Assessment to include breast, ovarian, pancreatic, and prostate cancers, according to a news release from NCCN.¹ The expansion follows a recent expansion of similar genetic risk assessment guidelines in colorectal, endometrial, and gastric cancers.²

Previous guidelines covered pathogenic/likely pathogenic (P/LP) variant assessment associated with increased risk for breast, ovarian, and pancreatic cancers.³ Specifically, the publication encompassed guidelines for BRCA1, BRCA2, CDH1, PALB2, PTEN, and TP53 testing, with recommended counseling and testing approaches, and care strategies, outlined for patients with these variants. Recently, testing criteria, which includes HOXB13 gene testing for prostate cancers, was added to the guidelines.

“These expanded guidelines reflect the recommendations from leading experts on genetic testing based on the latest scientific research across the cancer spectrum, consolidated into two convenient resources,” Crystal S. Denlinger, MD, chief executive officer of NCCN, stated in the press release.¹ “This information is critical for guiding shared decision-making between health care providers and their patients, enhancing screening practices as appropriate, and potentially choosing options for prevention and targeted treatment choices. Genetic testing guidelines enable us to better care for people with cancer and their family members.”

The previous guidelines outlined testing criteria, both generally and by cancer type. General testing criteria included individuals with a blood relative with a known P/LP variant in a cancer susceptibility gene, a P/LP variant identified on tumor genetic testing that has clinical implications identified in germline testing, and to aid in systemic therapy and surgical decision-making. Additionally, individuals who met Li-Fraumeni syndrome testing criteria, PTEN hamartoma tumor syndrome (PHTS)/Cowden syndrome (CS) testing criteria, or have Lynch syndrome, were included.

Furthermore, risks and management associated with gene testing was outlined, with screening recommendations made based on family P/LP status and testing outcome. Each P/LP variant included a gene summary which outlined absolute risk, management strategies, and strength of evidence of associated cancer based on the gene and cancer type identified. Strength of evidence of association with cancer was identified as very strong, strong, limited, or none, depending on available risk evaluation research.

The guidelines then offer specific management strategies for P/LP variants both generally and based on cancer site, specifically for BRCA mutations, Li-Fraumeni syndrome, and CS and PHTS. Management strategies include screening and surveillance procedure and interval, as well as recommendations for preventative surgeries or other interventions.

Specific risk reduction principles and strategies were outlined for transgender, non-binary, and gender diverse people with hereditary cancer syndromes, with focus on at-risk organs based on biologic sex at birth. Additionally, the guidelines include a list of genes and syndromes mentioned in other guidelines, as well as a list of abbreviations used throughout the publication.

“These guideline panels are continuously active and engaged, constantly responding to new evidence as it becomes available to provide the most up-to-date information to NCCN Guidelines users,” Mary B. Daly, MD, PhD, FACP, chair of the NCCN Guidelines Panel for Genetic/Familial High-Risk Assessment: Breast, Ovarian, Pancreatic, and Prostate at the Fox Chase Cancer Center, stated in the news release.¹ “These updates include the spectrum of genes associated with genetic syndromes, the range of risk associated with each pathogenic variant, the improvements in screening and prevention strategies, the role of genetic data to inform cancer treatment, and the expansion of the role of genetic counseling as this field moves forward.”

References

1. Cancer genetic risk assessment guidelines expand to meet growing understanding of hereditary risk. National Comprehensive Cancer Network. November 7, 2024. Accessed November 7, 2024.
2. National Comprehensive Cancer Network. Genetic/familial high-risk assessment: colorectal, endometrial, and gastric. Accessed November 7, 2024. https://www.nccn.org/professionals/physician_gls/pdf/genetics_ceg.pdf
3. National Comprehensive Cancer Network. Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Accessed November 7, 2024. https://www.nccn.org/professionals/physician_gls/pdf/genetics_bop.pdf