CHEK2 riskScore Clinical Scenario – Low Risk

A 41-year-old woman without a personal history of cancer presents to her provider to better understand her risk of breast cancer.

A 41-year-old woman without a personal history of cancer presents to her provider to better understand her risk of breast cancer. Her mother, maternal grandmother, and maternal great-aunt were all diagnosed with breast cancer in their 70s. Her provider uses the Tyrer-Cuzick model to estimate her lifetime risk of breast cancer to be 14.5%. It is generally recommended that women receive annual breast MRIs (in addition to their mammogram) when their lifetime breast cancer risk is estimated to be 20% or greater.1

Given the family history, the woman pursues genetic testing and her provider orders Myriad’s myRisk® Hereditary Cancer Test to analyze 35 genes related to hereditary cancer. Her result is positive for a pathogenic mutation in the CHEK2 gene. Studies of CHEK2 have estimated a lifetime breast cancer risk of 20-31% for women with pathogenic mutations.2 However, an added component of the myRisk test is a polygenic risk score (PRS) called riskScore®.

riskScore can refine a woman’s risk of breast cancer by incorporating the effects of 86 genetic variants called single nucleotide polymorphisms (SNPs). The CHEK2 modified riskScore has estimated this woman’s remaining lifetime risk for breast cancer to be 17.1%. Consequently, this woman may not need the increased breast screening that is typically recommended for women with CHEK2 pathogenic mutations. In fact, in the polygenic risk score validation study, nearly one in four women were moved into a lower risk category even though they had a pathogenic CHEK2 mutation.3

After being tested with the myRisk test, this woman now has a more comprehensive assessment of her breast cancer risk which allows for a more individualized plan for breast cancer screening and prevention.

Want to read the full study on the PRS validation of carrier modified riskScore? Click here.

References
  1. NCCN Clinical Practice Guidelines in Oncology. Breast Cancer Screening and Diagnosis (Version 1.2019). https://www.nccn.org/professionals/physician_gls/pdf/breast-screening.pdf. Accessed August 25, 2020.
  2. Kurian A, et al. Breast and Ovarian Cancer Penetrance Estimates Derived from Germline Multiple-Gene Sequencing Results in Women. JCO Precision Oncol. 2017.
  3. Gallagher S, et al. Association of a Polygenic Risk Score with Breast Cancer Among Women Carriers of High and Moderate-Risk Breast Cancer Genes. JAMA Netw Open 2020;3(7):e208501.

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