P215: The ACT ON Trial: Assisted Cascade Testing through Outreach and Navigation
Poster Presenter
Emily Epstein
Clinical Behavioral Health Specialist
Weill Cornell Medicine United States
Objectives
The ACT ON study will assess the effectiveness of facilitated cascade genetic testing in identifying at-risk individuals for hereditary cancer syndromes and enhancing the uptake of genetic testing among relatives.
Method
Our ongoing study recruits patients with hereditary cancer syndromes at WCM/NYP Hospitals in Brooklyn, Queens, and Manhattan. Interventions include helping carriers identify and contact at-risk relatives with information on accessing genetic testing. Completion of testing assessed at 6 months post.
Results
Preliminary quantitative data in our ongoing study collected during the period from 5/18/2023 to 02/24/2024 revealed promising outcomes. Between 5/18/2023 and 2/24/2024, The ACT ON Study of clinician-facilitated cascade genetic testing has enrolled 43 probands who designated 88 relatives for contact. Among these relatives, 57 (64.8%) were successfully contacted. Notably, 96.5% of the contacted relatives expressed interest in undergoing genetic testing. Demographic data was also collected including sex, ethnicity, variant type, education, and knowledge level of genetic testing. We have begun contacting relatives eligible for contact at the 6-month mark. Currently, 13 relatives have been successfully contacted, with 7 testing positive for mutations. Among these, 5 shared the same mutations as the proband, while 2 exhibited different mutations. The study's early findings support our our hypothesis that clinician-facilitated cascade genetic testing would outperform standard patient-mediated cascade testing. Ongoing data will be compared with the previously identified 36% success rate of standard patient-mediated cascade testing as revealed in our systematic review and meta-analysis of facilitated cascade testing vs. standard patient-mediated cascade testing (Frey et al., 2022). Further evaluation will measure the proportion of successfully contacted at-risk family members receiving genetic testing within six months from initial contact. We will also examine social determinants of health (SDOH) and comparable demographics affecting the proband's uptake of enrollment in cascade testing, such as relationship to at risk relatives, education, ethnicity, time elapsed since genetic testing, and mutation type.
Conclusion
In conclusion, the landscape of hereditary cancer syndromes underscores the critical importance of identifying individuals harboring pathogenic variants (PVs) in cancer-associated genes like BRCA1/2 and Lynch syndrome. These variants significantly elevate the lifetime risk of developing cancer, yet alarmingly, less than 5% of individuals with cancer-associated PVs are currently aware of their genetic predisposition.
Cascade genetic testing emerges as a vital tool in identifying at-risk individuals, involving the systematic testing of blood relatives of PV carriers. Despite its potential, significant barriers exist, with approximately one-third of relatives remaining uninformed of their hereditary risk. Even among those informed, less than half complete genetic testing, perpetuating the cycle of underdiagnosis and missed opportunities for personalized cancer risk reduction.
Our study highlights the potential of facilitated cascade genetic testing programs to address these challenges. The preliminary results of our clinician-facilitated cascade genetic testing program demonstrate considerable promise in identifying patients with hereditary cancer syndromes. It is imperative to recognize individuals at risk to facilitate personalized cancer treatment and prevention strategies effective. Leveraging medical team support, these early results suggest improved completion rates among relatives with facilitated cascade testing, thereby enhancing the effectiveness of cascade testing.
Moving forward, initiatives aimed at developing standardized protocols and resources for launching clinician-facilitated cascade programs are crucial. By empowering healthcare providers with the tools and support necessary to navigate the cascade testing pathway, we can improve the dissemination of genetic risk information and promote proactive measures for personalized cancer prevention and treatment.
