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.
Testing for CHEK2 genetic abnormalities (e.g., duplications, deletions) in the assessment of breast cancer risk is considered investigational.
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
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 http://jco.ascopubs.org.
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 https://www.evidencepositioningsystem.com/ (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)
ORIGINAL EFFECTIVE DATE: 4/14/2011
MOST RECENT REVIEW DATE: 12/13/2018
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