Current and new frontiers in hereditary cancer surveillance: Opportunities for liquid biopsy
Kirsten M. Farncombe, Derek Wong, Maia Norman, Leslie E. Oldfield, Julia A. Sobotka, Mark Basik, Yvonne Bombard, Victoria Carile, Lesa Dawson, William D. Foulkes, David Malkin, Aly Karsan, Patricia C. Parkin, Lynette S. Penney, Aaron Pollett, Kasmintan A. Schrader, Trevor J. Pugh, Raymond H. Kim, Adriana Aguilar‐Mahecha, Melyssa Aronson, Mark Basik, Nancy N. Baxter, Phil Bedard, Hal K. Berman, Marcus Q. Bernardini, Yvonne Bombard, Victoria Carile, Clarissa Chan, Tulin Cil, Blaise Clarke, Lesa Dawson, Irfan Dhalla, Christine Elser, Gabrielle Ene, Kirsten M. Farncombe, Sarah E. Ferguson, William D. Foulkes, Laura Genge, Robert Gryfe, Michelle Jacobson, Aly Karsan, Monika Kastner, Pardeep Kaurah, Raymond H. Kim, Josiane Lafleur, Jordan Lerner‐Ellis, Stéphanie Lheureux, Shelley M. MacDonald, Jeanna McCuaig, Brian Mckee, Nicole Mittmann, Maia Norman, Leslie E. Oldfield, Seema Panchal, Lynette S. Penney, Carolyn Piccinin, Aaron Pollett, Trevor J. Pugh, Dean A. Regier, Zoulikha Rezoug, Krista Rideout, Kasmintan A. Schrader, Kara Semotiuk, Sara Singh, Lillian L. Siu, Julia A. Sobotka, Sophie Sun, Emily Thain, Karin Wallace, Thomas R. Ward, Shelley Westergard, Stacy Whittle, Wei Xu, Celeste Yu
Abstract
At least 5% of cancer diagnoses are attributed to a causal pathogenic or likely pathogenic germline genetic variant (hereditary cancer syndrome-HCS). These individuals are burdened with lifelong surveillance monitoring organs for a wide spectrum of cancers. This is associated with substantial uncertainty and anxiety in the time between screening tests and while the individuals are awaiting results. Cell-free DNA (cfDNA) sequencing has recently shown potential as a non-invasive strategy for monitoring cancer. There is an opportunity for high-yield cancer early detection in HCS. To assess clinical validity of cfDNA in individuals with HCS, representatives from eight genetics centers from across Canada founded the CHARM (cfDNA in Hereditary and High-Risk Malignancies) Consortium in 2017. In this perspective, we discuss operationalization of this consortium and early data emerging from the most common and well-characterized HCSs: hereditary breast and ovarian cancer, Lynch syndrome, Li-Fraumeni syndrome, and Neurofibromatosis type 1. We identify opportunities for the incorporation of cfDNA sequencing into surveillance protocols; these opportunities are backed by examples of earlier cancer detection efficacy in HCSs from the CHARM Consortium. We seek to establish a paradigm shift in early cancer surveillance in individuals with HCSs, away from highly centralized, regimented medical screening visits and toward more accessible, frequent, and proactive care for these high-risk individuals.