Myriad opens hood on carriers of breast cancer risk genes

By Emily Hayes, LabPulse.com editor in chief

December 17, 2019 -- Myriad Genetics plans to offer more risk prediction information to women who carry mutations associated with breast cancer. Results from a validation study exploring the nature of high- and intermediate-risk pathogenic variants in women with European ancestry were presented on December 14 at the San Antonio Breast Cancer Symposium (SABCS).

The company currently offers hereditary cancer testing for women to determine their risk for breast cancer, with analysis/results based on mutation status. Those with high-risk or intermediate-risk mutations -- BRCA1, BRCA2, ATM, CHEK2, and PALB2 -- are notified that they are carriers. Those who do not test positive for genes with intermediate or high risk are given a polygenic risk score (PRS) for developing breast cancer based on testing for 86 single nucleotide polymorphisms (SNPs).

However, the company is now planning to integrate polygenic risk scoring for those who carry intermediate- and high-risk mutations. Myriad presented its analysis of how polygenic risk scoring might provide additional valuable information in carriers of mutations in a poster study at the SABCS meeting.

Who benefits most?

The study involved a total of 9,802 patients with intermediate- or high-risk mutations and 141,160 with no pathogenic variants. After adjusting for age and family cancer history, the company evaluated the 86-SNP PRS with invasive breast cancer for each gene type. The 86-SNP polygenic risk score was strongly associated with breast cancer risk for each of the intermediate- and high-risk mutations tested, as well as for those with no pathogenic variants.

Polygenic risk score significantly modifies estimates of lifetime breast cancer risk in carriers of intermediate- and high-risk mutations
Polygenic risk score significantly modifies estimates of lifetime breast cancer risk in carriers of intermediate- and high-risk mutations. Risk is significantly modified for carriers of BRCA1, BRCA2, CHEK2, ATM, and PALB2 pathogenic variants, though with different effect sizes. Image courtesy of Myriad Genetics.

"The 86-SNP PRS significantly modifies risk for carriers of BRCA1, BRCA2, CHEK2, ATM and PALB2 [pathogenic variants] albeit with apparently different effect sizes," Myriad Chief Scientific Officer Jerry Lanchbury, PhD, and colleagues reported in the study poster. "These results indicate that risk estimates employing polygenic scores may need to be derived separately for each gene."

Risk was modified the most in those with CHEK2, ATM, and PALB2 mutations. In fact, in carriers of a relatively high-risk gene such as CHEK2, risk was radically modified for those who also carried protective combinations of polygenic risk SNPs, Lanchbury explained in an interview. Those in the highest 86-SNP PRS quintile had a 1.7-fold higher risk than those in the middle quintile, Myriad reported.

The company is in the process of determining how it could combine PRS with carrier status clinically. It also would like to combine genetic results with clinical and biological risk factors that it already reports for noncarriers, for example, age of menarche and menopause and the number of children. Myriad plans to publish the poster study results for women with European ancestry in a peer-reviewed journal, and a study of risk scoring in African American women is ongoing.

The study comes at a time of scrutiny for genetic testing in breast cancer patients. This month, the U.S. National Comprehensive Cancer Network (NCCN) broadened its guidance on genetic testing to include a broad range of variants beyond BRCA1 and BRCA2 in patients with breast or ovarian cancer. The move could pave the way for greater reimbursement of genetic testing.

On the other hand, the American College of Medical Genetics and Genomics (ACMG) just issued a statement against universal testing in breast cancer patients, citing a range of reasons, including uncertainty over the significance of mutations other than BRCA1/2 detected with multigene panel testing.

Liquid biopsy boosts the odds in triple-negative breast cancer
Circulating tumor DNA test results were significantly associated with disease-free survival in women with early triple-negative breast cancer in a phase...
Genetics group makes case against testing all with breast cancer
The American College of Medical Genetics and Genomics (ACMG) highlighted the lack of evidence for universal testing of breast cancer patients for BRCA1/2...
Agendia's MammaPrint refines risk scoring in younger cancer patients
Agendia's MammaPrint 70-gene panel can be used to refine risk in patients 50 years of age and younger with early breast cancer, which may be helpful in...
CVS Health paves way for genetic testing of cancer patients
CVS Health is launching a program that will facilitate genetic testing for cancer patients at the point of prescribing to guide personalized treatment...
Myriad to seek further BRACAnalysis CDx FDA approval
Myriad Genetics plans to seek supplementary premarket approval from the U.S. Food and Drug Administration (FDA) for an additional application of its BRACAnalysis...

Copyright © 2019 LabPulse.com

Last Updated np 12/16/2019 6:18:38 PM



Register below for our weekly Letter from the Editor to receive the latest Clinical Lab news and insights.
Email