Results from a second major clinical validation study of the polygenic RiskScore test produced by Myriad Genetics Inc, Salt Lake City, were featured at the 2018 annual meeting of the American Society of Clinical Oncology.1

The RiskScore test combines more than 80 DNA variants with family and medical history to determine a woman’s 5-year and lifetime risk of breast cancer. The key finding from the newly presented prospective clinical trial is that the RiskScore test can accurately predict the 5-year and lifetime risk of breast cancer among women who test negative for a hereditary mutation using the company’s myRisk hereditary cancer test.

“Women who undergo hereditary cancer testing and test negative for mutations in known breast cancer genes frequently still have questions about their risk of breast cancer,” says Johnathan Lancaster, MD, PhD, gynecologic oncologist and chief medical officer at Myriad Genetics. “RiskScore answers many of those questions by providing a definitive risk determination with a test that has been highly validated.”

RiskScore is a clinically validated personalized medicine tool that enhances Myriad’s myRisk hereditary cancer test. RiskScore helps to predict a woman’s lifetime risk of developing breast cancer using clinical risk factors and genetic markers found throughout the genome. The test incorporates data from 86 DNA variants, called single-nucleotide polymorphisms (SNPs), identified through 20 years of genomewide association studies in breast cancer. The test was validated in Myriad’s laboratory to predict breast cancer risk among women of European descent. Data from the test are combined with a best-in-class family and personal history algorithm, the Tyrer-Cuzick model, to provide every eligible patient with an individualized breast cancer risk score.

The objective of the newly presented study was to independently validate the RiskScore test in a prospective, general patient population. The study included 518 women: 256 women recently diagnosed with breast cancer, and 262 unaffected women (controls). Study results indicate that RiskScore is a highly statistically significant predictor of the 5-year and lifetime risk of breast cancer (p = 2.6 x 10–12 and p = 2.5 x 10–12, respectively).

Moreover, RiskScore was statistically significantly superior to the Tyrer-Cuzick model alone for both 5-year and lifetime risk of breast cancer (1.9 x 10– 8 and p= 2.4 x 10–8, respectively), underscoring the independent contribution of the SNPs to the combined test score. Importantly, a separate analysis of the 86 SNPs among women in the control group showed that about half of the women tested had an increased risk of breast cancer compared to the general population.

“Individually, the 86 DNA variants may have a small effect on breast cancer risk. However, this study shows that when you combine them, it is possible to more accurately predict a woman’s risk of breast cancer versus relying on family history and clinical features alone,” says Kathryn Dalton, DO, lead investigator and breast surgeon at Cape Cod Healthcare General and Specialty Surgery. “Importantly, this genetic information can be used to identify those women who are at normal risk and can be followed with routine screening, and those who are at higher risk and may benefit from additional monitoring.”

The RiskScore test is currently available for women of European descent who receive a negative myRisk hereditary cancer test result. However, every patient tested with the myRisk hereditary cancer test, regardless of ethnicity, receives their lifetime breast cancer risk estimates according to the Tyrer-Cuzick model, which estimates risk based on family history and clinical features. Myriad is working to expand the RiskScore test to include other ethnicities.

For further information, visit Myriad Genetics.


  1. Dalton K, Hughes E, Hedegard W, et al. Validation of a combined residual risk score for healthy unaffected women presenting to breast cancer (BC) screening centers [abstract]. Oral presentation 1507 to the 2018 annual meeting of the American Society of Clinical Oncology, Chicago, June 1–5, 2018. Available at: Accessed July 1, 2018.