SABCS 2017: Combined Residual Risk Score Test and Predicting Breast Cancer Risk in Women Who Tested Negative for Hereditary Mutations

Results from a validation study to better define the risk of breast cancer in women of European ancestry who tested negative for a hereditary cancer mutation with a hereditary cancer risk test (myRisk Hereditary Cancer test) were reported earlier this week in a spotlight presentation at the 2017 San Antonio Breast Cancer Symposium (Abstract PD1-08). Elisha Hughes, PhD, of Myriad Genetics, Salt Lake City, was the first author of the study, which was included in a poster discussion. Julie Nangia, MD, of Baylor College of Medicine, Houston, discussed the study.

The study was designed to validate the ability of the enhanced hereditary test (myRisk Hereditary Cancer with riskScore) to predict a woman’s 5-year risk and lifetime risk of breast cancer compared with the Tyrer-Cuzick model alone. The Tyrer-Cuzick model looks into a person’s history including age, Ashkenazi Jewish heritage, family cancer history, child birth history, along with height and weight to determine a person’s lifetime risk for breast cancer compared with standard risk in a woman without a family history of cancer.

The new test combines data from this model with 86 genetic markers, called single nucleotide polymorphisms (SNPs), to comprise a combined risk score that accounts for clinical, familial, and genetic variables. Currently less than 10% of unaffected women with a strong family history of breast cancer test positive for mutations in breast cancer risk genes (ie, BRCA1, BRCA2, and others).

Validation Study and Analysis in the Real World

The validation study of the combined residual risk score test included 1,617 women: 990 women with a breast cancer diagnosis within 1 year of multigene testing and 627 unaffected women who had genetic testing for hereditary nonpolyposis colon cancer and no cancer history of any type. The results showed the combined residual risk score test was a highly statistically significant predictor of breast cancer risk at 5 years (P = 5.2 x 10-39) and over a woman’s lifetime (P = 4.1 x 10-35). Moreover, the new test was statistically significantly superior to the Tyrer-Cuzick model alone for predicting both 5-year and lifetime risks of breast cancer in this population.

In a separate analysis reported by the authors, the combined residual risk score test and the Tyrer-Cuzick models were evaluated in a large clinical cohort of 6,479 unaffected women who tested negative for mutations in 11 genes associated with hereditary breast cancer to determine their remaining lifetime risk of developing breast cancer. The results showed the new enhanced hereditary test predicted remaining lifetime risk estimates ranging from 0.88% to 66%. Additionally, 38% of women tested with the enhanced hereditary test had a lifetime risk higher than 20%, and 7% had a lifetime risk more than 35% than the general population. Women with a greater than 20% lifetime risk of breast cancer are candidates for additional screening based on U.S. Preventive Services Task Force recommendations; women with above a 35% risk may be candidates for more aggressive medical interventions.

The authors stated that the combined residual risk score was highly predictive of risk of breast cancer development in unaffected women with hereditary cancer risk factors after testing negative for known risk mutations. When combining this residual risk score with genetic and family history risk factors, the combined residual risk score was a better predictor of risk for breast cancer than genetic and family histories alone. In conclusion, the authors reported “the combined residual risk score in women at risk for hereditary breast cancer may offer significant potential for the management of greater than 90% of high-risk women who test negative for monogenic mutations in breast cancer susceptibility genes.”

Johnathan Lancaster, MD, PhD, Chief Medical Officer, Myriad Genetics, said: “This comprehensive approach to lifetime breast cancer risk assessment includes 28 genes, family history evaluation, and well-validated SNPs, and it delivers the most precise tool available to help physicians assess a woman’s breast cancer risk.”

Disclosure: The authors of the study are employees of Myriad Genetics.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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