Universal Germline Testing for Hereditary Cancer Risk: Identification of At-Risk Individuals Missed By Guidelines Using a Genetics Copilot

Category: Genetic Counseling, ELSI, and Education

Learning objective: Identify approaches to universal genetic testing that increase the detection of at-risk individuals that would be missed by current testing guidelines.

Background

Patients referred for germline genetic testing (GT) have typically been selected using guidelines based on personal and family history of cancer, age, and ancestry. Guidelines may miss people with pathogenic variants (PV) that could benefit from management recommendations. We launched a pilot to evaluate the implementation and outcomes of a universal germline hereditary cancer GT model at a hybrid community-academic cancer center. Effectiveness in identifying individuals with PV who may not meet GT criteria was assessed.

Methods

Data was collected from December 1, 2024, to March 31, 2025. All new patients received a pre-visit link to complete a genetics questionnaire, review education, and consent to GT. Eligibility included adults with no bone marrow transplant, active hematologic malignancy, or prior GT after 2013. A genetics copilot software automated the workflow, including cancer risk assessment (CRA), test ordering, clinical decision support for care plans and result delivery. Patients meeting criteria were informed of likely insurance coverage; others were advised of potential self-pay. Blood samples were collected post-visit, and testing was performed using a multigene panel. Results were integrated into the electronic medical record and disclosed via phone or platform, based on result type.

Results

Of 3,786 patients contacted, 2,915 patients (77%) activated the link, and 2,298 patients (79% of activated) completed the CRA. 273 patients (11%) were disqualified; 263 for GT after 2013, 10 for bone marrow transplant history. Among the completed CRA, 2,025 patients (88%) were eligible for consent, and 731 consented. GT was ordered for 545 patients (75%).

Among 504 results, 7% (n=37) were Positive, 3% (n=14) were Carrier, 34% (n=171) were Variant of Uncertain Significance (VUS), and 56% (n=282) were Negative. Notably, 41% (n=15) of positive patients did not meet criteria, and 19% (n=7) did not meet criteria and were unaffected. Among Positive patients not meeting criteria, PV in 19 genes were identified.

Conclusions

This work supports more inclusive testing strategies to improve access to precision oncology and preventative care. With the right workflow and automation, universal germline GT is both feasible and effective in identifying at-risk individuals missed by guideline-based approaches. Reminders for sample collection have been added to close the gap between consented and tested patients. Improved data collection to minimize excluded patients will further strengthen this model.