BlueCross BlueShield of Tennessee Medical Policy Manual

Genetic Testing for CHEK2 Mutations for Breast Cancer

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018


Mutations in the CHEK2 gene may be associated with a moderate risk of breast cancer. Testing for CHEK2 variants has been proposed for use in risk stratification in individuals with a family history consistent with hereditary breast cancer and for prognosis of breast cancer in individuals with breast cancer.

While some cancers associated with highly penetrant genes (e.g., BRCA1, BRCA2, PALB2) have established clinical management guidelines for individuals identified as having a pathogenic variant, there are no specific treatment recommendations for individuals testing positive for the CHEK2 variant beyond standard surveillance of breast self-exams and annual mammograms.

Note: This policy only addresses single-gene testing. CHEK2 may be included in breast cancer (hereditary) gene panels.




Clinical management recommendations for breast cancer-associated genes with moderate penetrance, such as CHEK2, are not standardized, nor is it known if testing for CHEK2 variants will lead to improved health outcomes.  


Aloraifi, F., McCartan, D., McDevitt, T., Green, A.J., Bracken, A. & Geraghty, J. (2015). Protein-truncating variants in moderate-risk breast cancer susceptibility genes: a meta-analysis of high-risk case-control screening studies. Cancer Genetics, 208 (9), 455-463. Abstract retrieved February 11, 2016 from PubMed database.

BlueCross BlueShield Association. Evidence Positioning System. (9:2020). Moderate penetrance variants associated with breast cancer in individuals at high breast cancer risk. (2.04.126). Retrieved July 13, 2021 from (52 articles and/or guidelines reviewed)

Buys, S., Sandbach, J., Gammon, A., Patel, G., Kidd, J., Brown, K., et al. (2017). A study of over 35,000 women with breast cancer tested with a 25-gene panel of hereditary cancer genes. Cancer, 123 (10), 1721-1730. Abstract retrieved November 13, 2017 from PubMed database.

Couch, F., Shimelis, H., Hu, C., Hart, S., Polley, E., Na, M., et al. (2017). Associations between cancer predisposition testing panel genes and breast cancer. JAMA Oncology, 3 (9), 1190-1196. (Level 3 evidence)

Easton, D., Pharoah, P., Antoniou, A., Tischkowitz, M., Tavtigian, S., Nathanson, K., et al. (2015). Gene-panel sequencing and the prediction of breast-cancer risk. The New England Journal of Medicine, 2243-2257. (Level 3 evidence)

Li, J., Meeks, H., Feng, B., Healey, S., Thorne, H., Makunin, I. et al. (2016). Targeted massively parallel sequencing of a panel of putative breast cancer susceptibility genes in a large cohort of multiple-case breast and ovarian cancer families. Journal of Medical Genetics, 53 (1), 34-42. (Level 3 evidence)

Massink, M., Kooi, I., Martens, J., Waisfisz, Q., & Meijers-Heijboer, H. (2015). Genomic profiling of CHEK2*1100delC-mutated breast carcinomas. BioMed Central, 15, 877. (Level 3 evidence)

National Comprehensive Cancer Network. (2.2021). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Genetic/familial high-risk assessment: breast, ovarian, and pancreatic. Retrieved July 13, 2021 from the National Comprehensive Cancer Network.

Weischer, M., Nordestgaard, B., Pharoah, P., Bolla, M., Nevanlinna, H., van’t Veer, L., et al. (2012). CHEK2 1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer. Journal of Clinical Oncology, 30 (35), 4308-4316. (Level 2 evidence)




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