Precision Prevention: The Current State and Future of Genomically Guided Cancer Prevention

Nawal Kassem, MD; Leigh Anne Stout, MS, LCGC; Cynthia Hunter, MS, LCGC; Bryan Schneider, MD; and Milan Radovich, PhD


JCO Precis Oncol. 2020;4:96-108. 

In This Article

Abstract and Introduction


The identification of cancer-predisposing germline variants has potentially substantial clinical impact for patients and their families. Although management guidelines have been proposed for some genes, guidelines for other genes are lacking. This review focuses on the current surveillance and management guidelines for the most common hereditary cancer syndromes and discusses some of the most pivotal studies supporting the available guidelines. We also highlight the gaps in the identification of germline carriers, the cascade testing of at-risk relatives, and the challenges impeding the proper follow-up and optimal management of pathogenic germline carriers. The anticipated surge in the number of identified germline carriers, deficient management guidelines, poor cascade testing uptake, and long-term follow-up necessitate the development of multidisciplinary clinics as an obligatory step toward the improvement of cancer prevention.


The leaps in technologic advancements and the nature of cancer as a genomically driven disease have propelled oncologists to the forefront of the precision medicine era. Until recently, pathogenic germline variants were primarily identified by testing conducted through the treating oncologist or via referral to familial cancer clinics. However, with the advent of next-generation sequencing (NGS), we are beginning to identify patients with pathogenic germline variants who would not have met criteria for genetic testing based on clinical history or other traditional parameters.

Given the potential clinical impact on patients and their biologic family members, it is important that the identification of pathogenic germline variants is not discounted. Here, we discuss current surveillance and management guidelines for patients with the most common hereditary cancer syndromes and other known cancer susceptibility genes. We also highlight the gaps within the current practice and the need for a multidisciplinary approach for the management of affected individuals and their family members.