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Combined score enhances understanding of breast cancer risk
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SAN ANTONIO — A risk score based on clinical, familial and genetic factors improved 5-year and lifetime predictions of breast cancer risk among women who tested negative for hereditary cancer mutations, according to results of a validation study presented at the San Antonio Breast Cancer Symposium.
“For women with a family history of breast cancer who tested negative for a hereditary cancer mutation, there was a need to provide them additional information about their remaining lifetime risk for breast cancer,” Johnathan Lancaster, MD, PhD, chief medical officer of Myriad Genetics, told HemOnc Today. “Only 10% of women test positive for a hereditary cancer mutation, and the remaining 90% who test negative are in need of such a test.”
Research has identified single nucleotide polymorphisms that, when expressed together, may partially explain breast cancer genetic susceptibility. Other risk factors are related to reproductive and medical history.
To include nongenetic factors in risk assessment, researchers developed a combined polygenic residual risk score by joining data from the Tyrer-Cuzick model — which evaluates family history, endogenous hormonal factors, benign disease, risk factors such as age and BMI, and genetic factors — with 86 SNPs. The new version of the myRisk (Myriad Genetics) test provides a numeric “riskScore.”
“It's the first and only test on the market that combines a 28-gene panel plus 86 SNPs and other clinical features to provide the most comprehensive breast cancer risk assessment available today,” Lancaster said. “We believe this information will identify many more women at high risk for breast cancer and will help physicians develop personalize treatment plans based on each patient's unique risk profile.”
Researchers identified these SNPs by evaluating data from training (n = 24,259) and validation (n = 10,575) cohorts of women who tested negative for 11 mutations associated with hereditary breast cancer: BRCA1, BRCA2, TP53, PTEN, STK11, CDH1, PALB2, CHEK2, ATM, NBN and BARD1.
Researchers found that the residual risk score strongly correlated with personal history of breast cancer (OR per unit increase in score = 1.41; 95% CI, 1.33-1.49).
“The combination of the SNP panel with Tyrer-Cuzick provides even greater precision than previously demonstrated from family models,” Jerry Lanchbury, PhD, chief scientific officer at Myriad Genetics, said in a press release. “As a result, we believe our myRisk Hereditary Cancer test, now enhanced with riskScore, provides the most comprehensive breast cancer risk assessment available today.”
A validation case-control study of the model included 1,617 women, 990 of whom had breast cancer. Results showed the riskScore was a significant predictor of a woman’s 5-year (P = 5.2 x 10–39) and lifetime (P = 4.1 x 10–35) risks for breast cancer.
The test also better predicted 5-year (P = 1 x 10–12) and lifetime (P = 8.3 x 10–13) risks for breast cancer than the Tyrer-Cuzick model alone.
Results showed lifetime risk estimate based on riskScore ranged from 0.88% to 66.4%. This included 38.2% of patients who had a lifetime risk that exceeded 20%, and 7.4% with more than three times the lifetime risk of the general population.
“These data confirm the important contribution of SNPs to breast cancer risk assessment in unaffected women who test negative for mutations in hereditary breast cancer genes with a precise measure of breast cancer risk,” Lanchbury said. “The addition of the SNP data appears to be especially helpful in identifying those patients at higher risk for developing breast cancer.” – by Alexandra Todak
Reference:
Hughes E, et al. Abstract PD1-08. Presented at: San Antonio Breast Cancer Symposium; Dec. 5-9, 2017; San Antonio.
Disclosures: The authors, Lancaster and Lanchbury report employment with Myriad Genetics.