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 (e.g. BreastNext™) 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.




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 changes in patient management or 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.

American Society of Clinical Oncology. (2015, November). American Society of Clinical Oncology policy statement update: genetic and genomic testing for cancer susceptibility. Retrieved November 13, 2017 from

BlueCross BlueShield Association. Evidence Positioning System. (7:2018). Moderate penetrance variants associated with breast cancer in individuals at high breast cancer risk. Retrieved October 18, 2018 from (48 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., and Meijers-Heijboer, H. (2015) Genomic profiling of CHEK2*1100delC-mutated breast carcinomas. BioMed Central. 15:877 (Level 3 evidence)

National Comprehensive Cancer Network. (2.2019). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Genetic/familial high-risk assessment: breast and ovarian. Retrieved October 18, 2018 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)




Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

This document has been classified as public information.