Ambry Genetics, Aliso Viejo, Calif, a clinical genetics testing company, says data from the largest cohort study of its kind presents “novel, detailed evidence” for improving the guidelines that determine which patients are at risk for cancer.

Clinicians use guidelines to inform decisions about which patients should receive genetic testing for hereditary cancer and for those patients which genes should be tested. Such guidelines also have implications for how insurance plans cover genetic testing and for appropriate medical management of patients after testing is complete.

In a recent study, researchers from Ambry and the Mayo Clinic applied genetic testing criteria from the National Comprehensive Cancer Network clinical practice guidelines in oncology to 165,000 patients who underwent multigene, hereditary cancer panel testing.1


Holly LaDuca, Ambry Genetics.

Ambry specifically looked at the testing guidelines for BRCA-related breast and/or ovarian cancer syndrome and for Lynch syndrome to better understand how the guidelines for these two common, inherited conditions might be improved to identify more at-risk patients.

The study found that updating the BRCA1 and BRCA2 and Lynch syndrome testing criteria to include more medically actionable, cancer-predisposition genes—and relaxing current criteria, such as age-at-diagnosis constraints—would identify more patients at risk for developing hereditary cancer. The study found that:

  • One in four patients (409/1518) with pathogenic variants in Lynch syndrome genes would have been missed using current Lynch syndrome testing criteria.
  • One in 17 patients (302/5200) with pathogenic variants in BRCA1 and BRCA2 would have been missed using current BRCA1 and BRCA2 testing criteria.
  • Three in five patients (7647/12,847) with pathogenic variants in clinically actionable breast and/or ovarian cancer genes would have been missed if tested for BRCA1 and BRCA2 only.

“This study identifies specific opportunities to expand the current testing guidelines to identify more individuals facing increased cancer risks and who would benefit from more intensive cancer surveillance and/or preventive surgeries,” says Holly LaDuca, lead author and senior manager for clinical affairs research at Ambry Genetics.

In addition, the study revealed several new gene-cancer associations that have the potential to affect patient care. For example, pathogenic variants in BARD1 were associated with a two-fold increased risk for breast cancer. However, there are no recommendations for increased breast cancer surveillance for these variants, as there are for other genes associated with similar risk.

“Results from this study refined several gene-cancer associations for which there are no recommendations for increased surveillance and/or preventive surgeries,” says LaDuca. “More studies are needed from the genetics community to better understand how these new gene-cancer associations have the potential to impact patient care.”

For more information visit Ambry Genetics.


  1. LaDuca H, Polley EC, Yussuf A, et al. A clinical guide to hereditary cancer panel testing: evaluation of gene-specific cancer associations and sensitivity of genetic testing criteria in a cohort of 165,000 high-risk patients. Genet Med. Published online August 13, 2019; doi: 10.1038/s41436-019-0633-8.

Featured image:

Laboratory setting at Ambry Genetics.