Multi-Gene Panel Testing Catches Cancer Risk Variants

Over 608,000 patients with ovarian, breast, pancreatic, prostate and colorectal cancer are diagnosed each year. Current guidelines recommend testing all patients with ovarian and pancreatic cancer, as well as patients with prostate, breast and colorectal cancer (CRC) who meet certain criteria.

However such guidelines say little about the role of expanded multi-gene panel testing in these patients. Studies have begun to show that germline testing using comprehensive multi-gene panels identifies clinically actionable mutations in genes other than those recommended per the patient’s cancer type, at a very modest incremental cost of uncovering these additional mutations.


A team of scientists collaborating with the genetic testing company Invitae (San Francisco, CA, USA) analyzed de-identified sequence data for 83 cancer-risk genes in patients with 81,861 breast, 11,124 ovarian, 9,669 CRC, 5,794 prostate, and 4,659 pancreatic cancer referred for hereditary cancer genetic testing. These genes were assessed uniformly for all patients in this study, regardless of the specific genes ordered by clinicians based on personal/family history.

The team compared the positive rate for each cancer type, where a positive report was defined by the presence of a likely pathogenic (LP) or pathogenic (P) variant. Positive rates for a minimal gene panel for the respective indication (e.g. BRCA1/2 or the five Lynch Syndrome [LS] genes) were computed and compared to the positive rates when the comprehensive 83 gene panel was analyzed.

When the Invitae Multi-Cancer 83-gene comprehensive panel was applied, the overall diagnostic yield for all 113,107 patients with breast, ovarian, pancreatic, prostate and CRC increased almost 4-fold to 16%. Excluding mono-allelic P/LP variants in predominantly recessive cancer-risk genes (e.g. MUTYH) reduces the diagnostic yield to 13%. Stratified by cancer type, and removing mono-allelic recessives, positive yield was: breast 11.8%, ovarian 18%, prostate 15%, pancreatic 16% and CRC 19%.

The authors concluded that their study suggests that genetic testing guidelines should be expanded to include clear recommendations supporting multi-gene panel testing in patients with cancer, to improve the care of patients and their family members. Robert Nussbaum, MD, Invitae's chief medical officer, said, “Genetic test panels that include just a few of the clinically important genes provide incomplete genetic information for patients and their clinicians, both in terms of informing treatment choices and identifying additional health risks. The study was presented at the American College of Medical Genetics and Genomics annual meeting held April 2-6, 2019, in Seattle, WA, USA.

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