NCCN and ASCO Broaden Criteria for Hereditary Cancer Testing

Professional guidelines that determine who qualifies for hereditary cancer genetic testing have been widening in scope. Recent revisions from the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology (ASCO) reflect a recognition that testing criteria built around narrow age cutoffs or single tumor types were missing patients who carry clinically significant variants.

NCCN’s hereditary breast and ovarian cancer guidance now extends to people diagnosed with breast cancer between ages 45 and 49, and hereditary prostate cancer has been folded into the same guideline set, now covering hereditary breast, ovarian, prostate, and pancreatic cancers with updated testing criteria for genes including ATM, BRCA1, BRCA2, CHEK2, HOXB13, and TP53. NCCN now recommends considering genetic testing for anyone diagnosed with prostate cancer at age 55 or younger.

On the colorectal and gynecologic side, NCCN recommends considering Lynch syndrome testing for all people with colorectal cancer, regardless of age or specific tumor features — a departure from older criteria that focused on younger patients or particular tumor markers.

NCCN’s shift toward universal Lynch syndrome testing for colorectal cancer patients follows findings that 16% of tested colorectal cancer patients carry a high-risk hereditary gene variant.

New recommendations also call for hereditary cancer screening for all individuals with newly diagnosed endometrial cancer, along with enhanced guidance for evaluating and managing CDH1-associated gastric cancer risk. At the same time, NCCN has moved away from intensive colorectal screening protocols for people with CHEK2 pathogenic variants, instead basing screening on age, family history, personal history of polyps, and symptoms — a recognition that broader testing needs to be paired with more individualized, rather than uniformly aggressive, follow-up.

ASCO’s guidance has moved in a similar direction. New ASCO guidelines for germline genetic testing in patients with cancer were published in May 2024, and joint ASCO and Society of Surgical Oncology guidelines from April 2024 recommend offering BRCA1 and BRCA2 testing to all individuals newly diagnosed with breast cancer at age 65 or younger, with additional criteria — such as a known family mutation or an early-onset relative — extending the recommendation to older patients as well.

Underneath these clinical guidelines sits the technical standard used to interpret what a genetic test result actually means. The American College of Medical Genetics and Genomics (ACMG), together with the Association for Molecular Pathology, has used a 2015 framework built on 28 evidence criteria to classify variants into five categories: Pathogenic, Likely Pathogenic, Variant of Uncertain Significance, Likely Benign, or Benign. A forthcoming update, referred to as SVC v4.0, is being jointly developed by ACMG, AMP, the College of American Pathologists, and ClinGen, and is expected to replace the current categorical combining rules with a Bayesian points system.

For patients and families, the practical takeaway is that testing eligibility has genuinely expanded. Someone who was told a few years ago that they didn’t meet criteria for genetic counseling referral — because of their age at diagnosis, their specific cancer type, or a thin family history — may meet current guidelines today. Ongoing variant re-evaluation also means that a result classified as uncertain in the past may since have been reclassified, which is one reason professional guidelines increasingly emphasize periodic follow-up with a genetic counselor rather than treating a test result as a one-time answer.