Genetic Testing Today

Background: The commercial introduction of next-generation sequencing has made it possible to test for mutations in all known or suspected breast cancer predisposition genes in one panel, at one time, for about the same cost as a BRCA gene test. Clinicians are increasingly presented with the challenge of advising patients with mutations in rare breast cancer predisposition genes. Methods: Literature review and personal experience with panel tests. Results: Panel tests are more likely to identify a variant of uncertain clinical significance than a deleterious mutation. In addition, not all of the genes included in panel tests are unequivocally linked to increased breast cancer risk, and for most genes the penetrance is highly variable, making it difficult to translate a specific mutation into an absolute breast cancer risk. The three-generation cancer family history should be used to select truly high-risk families for panel testing, and then referred to again when the results are received in order to guide risk-management decisions. Knowing a breast cancer patient’s mutation status can influence decisions about local–regional and systemic therapy, but turnaround times for many tests are still too long to incorporate them into the initial evaluation of a new breast cancer. Conclusion: The commercialization of next-generation sequencing has the potential to greatly enhance the identification and management of individuals with an inherited predisposition to breast cancer. A period of uncertainty is anticipated before the full potential of this new technology is realized.