Published online Mar 28, 2016. doi: 10.5412/wjsp.v6.i1.13
Peer-review started: August 23, 2015
First decision: October 27, 2015
Revised: December 12, 2015
Accepted: January 5, 2016
Article in press: January 7, 2016
Published online: March 28, 2016
Processing time: 216 Days and 1.5 Hours
Clinical testing of patients for hereditary breast and ovarian cancer syndromes began in the mid-1990s with the identification of the BRCA1 and BRCA2 genes. Since then, mutations in dozens of other genes have been correlated to increased breast, ovarian, and other cancer risk. The following decades of data collection and patient advocacy allowed for improvements in medical, legal, social, and ethical advances in genetic testing. Technological advances have made it possible to sequence multiple genes at once in a panel to give patients a more thorough evaluation of their personal cancer risk. Panel testing increases the detection of mutations that lead to increased risk of breast, ovarian, and other cancers and can better guide individualized screening measures compared to limited BRCA testing alone. At the same time, multi-gene panel testing is more time-and cost-efficient. While the clinical application of panel testing is in its infancy, many problems arise such as lack of guidelines for management of newly identified gene mutations, high rates of variants of uncertain significance, and limited ability to screen for some cancers. Through on-going concerted efforts of pooled data collection and analysis, it is likely that the benefits of multi-gene panel testing will outweigh the risks in the near future.
Core tip: Evaluating multiple genes in a panel test has clear advantages over BRCA1/2 testing including a greater likelihood of identifying patients with actionable pathogenic mutations, improved efficiency over sequential testing, and lower overall cost. At the same time, panel testing comes with limitations; most notably a lack of clear management guidelines for mutations in moderate penetrance genes and limited evidence-based clinical validity. As more information is gathered on these moderate- and low-penetrance gene mutations, the ability to guide clinical decisions for patients will continue to improve.