Introduction:

We report a pilot implementation study conducted through a virtual telehealth prevention platform designed to translate genomic risk information into actionable prevention and early detection strategies, with initial deployment in the employer/member benefit setting. The convergence of rapidly advancing genetic science with dramatically decreasing costs has created an unprecedented opportunity to transform cancer care from reactive treatment to proactive prevention through universal genetic testing. While currently concentrated in resource-rich nations, the compelling benefits of this technology suggest inevitable global adoption as costs continue to decline and accessibility expands.

Methods:

All eligible members received email invitations with portal access links. Following informed consent, participants completed multigenerational pedigree analysis, medical history documentation, and environmental exposure assessments before receiving buccal swab kits shipped to their homes. Whole genome sequencing (30x coverage) was performed, with initial reporting focused on an enhanced ACMG gene list (n=151) and a multi-ancestry polygenic risk score (PRS) integrated breast cancer risk model. Individuals identified with elevated cancer risk received genetic counseling, access to expert medical consultation, and Prevention Support Team navigation for guideline-based screening and prevention interventions, with actionable summaries communicated to each member's primary care physician.

Results:

We report outcomes for 366 asymptomatic employees who completed the process. The cohort had a mean age of 42.7 years (range 22-63); 51% were female; none had a personal cancer history. Testing identified 72 pathogenic monogenic variants (PV) among 62 members (17% of total participants). Of these, 19/72 (26.4%) PVs occurred in cancer predisposition genes: BRCA1 (4), BRCA2 (1), MSH6 (1), SDHB (1), MEN1 (1), CHEK2 (4), ATM (1), RAD51D (1), BRIP1 (2), HOXB13 (2), BARD1 (1), LZTR1 (1), and MITF (1), listed in order of penetrance. Notably, all four BRCA1 carriers were males with at-risk female relatives. The vast majority of participants were unaware of their genomic risk burden prior to study participation.

Conclusion:

We demonstrate successful implementation of population-level genomic risk stratification in an employer-based setting. Feasibility is confirmed by rapid engagement and substantial uptake among eligible members, yielding clinically actionable monogenic pathogenic variants and polygenic cancer risk assessments. This study uniquely included 49% male participants and a younger population than most published series. Critically, this approach revealed significant "missing heredity" that would have remained undetected using family history-based guidelines alone. The next phase focuses on implementing precision cancer prevention and screening strategies for asymptomatic individuals with elevated cancer risk. Multi-gene panel testing identifies actionable pathogenic variants that enable clinicians to implement risk-reduction strategies for new primary cancers, fundamentally shifting the paradigm from treatment to prevention.