CHEK2 riskScore Clinical Scenario – High 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 46-year-old woman without a personal history of cancer presents to her provider to better understand her risk of breast cancer. Her sister was diagnosed with breast cancer in her 30s and her paternal aunt had breast cancer at age 52. Her provider uses the Tyrer-Cuzick model to estimate her lifetime risk of breast cancer to be 27.1% and determines that she is a candidate for annual breast MRI screenings in addition to her annual screening mammograms.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 53.1%. Since her breast cancer risk is estimated to be higher than that typically associated with CHEK2 mutations, she may consider a more proactive medical management plan. Of note, in the polygenic risk score validation study, nearly one in seven women were moved into a risk category that placed them at higher risk (>50% breast cancer risk) than average pathogenic CHEK2 mutation ranges.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.

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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