Navigating the complex world of genetic testing can be daunting, especially with the rapidly evolving landscape of hereditary cancer testing. For healthcare providers, choosing the right hereditary cancer test and laboratory is crucial to offer the best care for their patients.
The Evolution of Hereditary Cancer Testing
Genetic testing was once limited to single-gene or single-syndrome tests (e.g. BRCA1/2). It then expanded to multigene panels addressing specific indications, such as breast and gynecologic cancer risk or colorectal cancer risk. However, advancements in genetics & genomics revealed that multiple genes can be linked to several types of cancer, and these risks often overlap. Because of this, pan-cancer multigene tests have become more common. These panels have a broader scope, examining multiple genes associated with several cancer types simultaneously.
Pan-cancer multigene panels can range in size, with some including as few as 30 genes and others encompassing 70+ genes. Panel size varies depending on the types of cancer risks they target as well as whether healthcare providers want to include only well-established cancer predisposition genes or also want to include genes with limited evidence linking them with cancer predisposition.
Why Choose a Pan-Cancer Multigene Test?
Pan-cancer multigene panels may provide a more holistic view of a patient's cancer risk profile. Consider the following:
• A patient may have a family history of several cancers or have limited family history information available. This can make it difficult to confidently choose a more targeted test.
• Some families have multiple pathogenic variants that contribute to their cancer histories.
• Many genes are associated with several cancer types, and there is often overlap in the risks from gene to gene.
• Recent updates in consensus guidelines recommend the use of multigene panel testing for certain patient populations.1 There are also medical management guidelines for many of the genes included in pan-cancer multigene panels, including Ambry’s CancerNext®.
By casting a wider net in comparison to disease-specific panels, healthcare providers are more likely to identify a disease-causing pathogenic variant(s) in their patient.
How to Choose the Right Pan-Cancer Multigene Test
When choosing the right pan-cancer multigene panel for your population or an individual patient, you should:
• Assess Patient or Population Needs: The first step in selecting the appropriate test is understanding the specific needs of your patient or patient population. It is important to consider their family history and how complete that history is, types of cancer present, and any previous genetic testing that they or their relatives may have undergone. If you are choosing one test to use for most of your patient population, consider what cancer risks you’d like it to address as well as whether you prioritize medical management guidelines being available for each gene.
• Evaluate Panel Size and Scope: Different panels vary in the number of genes they include and the types of cancers they target. A more targeted panel may suffice for patients with clear, more defined cancer family histories, while a pan-cancer panel may be necessary for those with complex or unknown family histories.
• Consider Clinical Utility: Many healthcare providers find it essential to choose a multigene panel that is more likely to provide clinically actionable results. Some tests include genes that are not definitively linked with cancer risk or that do not currently have medical management guidelines, which can complicate patient care. In fact, when a gene is not definitively linked with cancer risk, a variant in that gene cannot be classified higher (meaning pathogenic) than a variant of uncertain significance (VUS).
How to Choose the Best Laboratory Partner for Your Practice
There are many factors to consider when choosing the right lab partner for your practice. Some of these include:
• Scientific Rigor: Select a laboratory that prioritizes scientific excellence. You want to consider a lab that prioritizes gene characterization, uses advanced techniques like concurrent RNA analysis to support variant detection and characterization, and is committed to staying at the forefront of scientific innovation.
• Comprehensive Service: Beyond scientific capabilities, consider the overall service provided by the laboratory. Assess their transparency in billing, turnaround time for results, and customer support. A lab that offers a seamless experience from start to finish can enhance patient satisfaction and streamline your workflow.
• Patient Experience: The patient experience is a crucial aspect of genetic testing. Choose a lab that ensures affordability, provides clear communication, and offers support throughout the testing process.
Healthcare providers have many decisions to make as they work to provide the best possible care to their patients. When helping patients address their concerns related to a personal or family history of cancer, choosing the right hereditary cancer test and lab partner are crucial. It can help ensure that patients are more likely to receive accurate, actionable results, while the healthcare teams that care for them receive the support they need to keep providing excellent patient care.
1. Nadine Tung et al., Selection of Germline Genetic Testing Panels in Patients with Cancer: ASCO Guideline. JCO 42, 2599-2615(2024). DOI:10.1200/JCO.24.00662
