Genetic Testing for BRCA1, BRCA2 or CHEK2 for Breast or Ovarian Cancer
DESCRIPTION
Several genetic syndromes with an autosomal dominant pattern of inheritance that feature breast cancer have been identified. Of these, hereditary breast and ovarian cancer (HBOC) and some cases of hereditary site-specific breast cancer have in common causative mutations in BRCA genes. Families suspected of having HBOC syndrome are characterized by an increased susceptibility to breast cancer occurring at a young age, bilateral breast cancer, male breast cancer, ovarian cancer at any age, as well as cancer of the fallopian tube and primary peritoneal cancer. Hereditary site-specific breast cancer families are characterized by early onset breast cancer with or without male cases, but without ovarian cancer. For this policy, both will be referred to collectively as hereditary breast and/or ovarian cancer.
Germline mutations in the BRCA1 and BRCA2 genes are responsible for the cancer susceptibility in the majority of HBOC families, especially if ovarian cancer or male breast cancer are features. However, in site-specific breast cancer, BRCA mutations are responsible for only a proportion of affected families, and research to date has not yet identified other moderate or high-penetrance gene mutations that account for disease in these families. BRCA gene mutations are inherited in an autosomal dominant fashion through either the maternal or paternal lineage. It is possible to test for abnormalities in BRCA1 and BRCA2 genes to identify the specific mutation in cancer cases, and to identify family members with increased cancer risk. Family members without existing cancer who are found to have BRCA mutations can consider preventive interventions for reducing risk and mortality.
CHEK2 (cell cycle checkpoint kinase2) is also involved with DNA repair and human cancer predisposition like BRCA1 and BRCA2. CHEK2 is normally activated in response to DNA double-stranded breaks. CHEK2 regulates the function of BRCA1 protein in DNA repair and also exerts critical roles in cell cycle control and apoptosis. The CHEK2 mutation, 1100delC in exon 10 has been associated with familial breast cancers.
POLICY
BRCA1 or BRCA 2 genetic testing of individuals who have been diagnosed with breast or ovarian cancer is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Pre- and post-genetic counseling as adjunct to the BRCA1 or BRCA 2 genetic testing itself is considered medically necessary.
BRCA1 or BRCA 2 genetic testing of unaffected individuals (male or female) who are from families with a high risk of BRCA gene mutation considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Genetic testing of minors for BRCA1 and BRCA2 mutations is considered investigational.
Genetic testing of unaffected family members in the absence of a known BRCA1 or BRCA2 mutation in the family is considered investigational.
Testing for CHEK2 genetic abnormalities (mutations, deletions, etc.) in affected and unaffected individuals with breast cancer irrespective of the family history is considered investigational.
See also: Genetic Testing for HER-2
MEDICAL APPROPRIATENESS
Genetic testing for BRCA1 and BRCA2 is considered medically appropriate if ALL the following criteria are met:
ANY ONE of the following:
Individuals have been diagnosed with breast or ovarian cancer
Unaffected individuals (male or female) who are from families with a high risk of BRAC gene mutation as defined by ANY ONE of the following:
More than 2 breast cancer cases and one or more cases of ovarian cancer (in first or second-degree relatives) diagnosed at any age
More than 3 breast cancer cases (in first or second-degree relatives) regardless of the age at diagnosis
First-degree relatives with 2 of the following cancers diagnosed before age 50: 2 breast cancers, 2 ovarian cancers, or a breast and ovarian cancer
First-degree relatives with documented BRCA gene
Unaffected individuals of potentially high-risk populations (e.g., Ashkenazi Jewish descent)
Laboratories that conduct genetic testing must be certified with the Clinical Laboratory Improvement Act (CLIA), which is administered by the Health Care Financing Administration (HCFA) and the Centers for Disease Control and Prevention (CDC)
Genetic counselors must be licensed, certified, or eligible for board certification in their profession and must have specific training in cancer genetics. Genetic counselors must also be a member of a national genetics society or a national oncology society (National Cancer Institute requirement)
IMPORTANT REMINDER
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.
ADDITIONAL INFORMATION
Families at high risk for harboring a BRCA1 or BRCA2 mutation are those in which the incidence of breast or ovarian cancer in first (i.e., siblings, parents, offspring), or second (i.e., aunt, uncle, grandparent, or grandchild) degree relatives suggests an autosomal dominant inheritance (i.e. about half the family members are affected). Men rarely develop breast cancer, so there may not be an affected first-degree relative, and the size of the family may not permit analysis of possible autosomal dominant inheritance.
To ensure the adequate interpretation of the test, unaffected family members should be tested only after finding a mutation in an affected first- or second-degree relative. Therefore, the DNA from the unaffected family member can be tested specifically for the same mutation of the affected family member without having to sequence the entire gene. Testing an unaffected family member without knowing the genetic status of the family may lead to difficulties in interpreting the test results.
Information in published literature is not available to validate the application of genetic testing for BRCA1 and BRCA2 mutations on minors or for unaffected family members in the absence of a known BRCA1 or BRCA2 mutation in the family. Therefore, the impact on net health outcome is uncertain.
Information in published literature is not available to validate testing for CHEK2. Therefore, the impact on net health outcome is uncertain.
SOURCES
American College of Obstetricians and Gynecologists. (2009). News release. Routine screening for hereditary breast and ovarian cancer recommended. Retrieved December 13, 2010 from http://www.acog.org/from_home/publications/press_releases/nr03-20-09.cfm.
BlueCross BlueShield Association. Medical Policy Reference Manual. (2:2010). Genetic testing for hereditary breast and/or ovarian cancer (2.04.02). Retrieved December 8, 2010 from BlueWeb. (43 articles and/or guidelines reviewed)
Iniesta, M. D., Gorin, M. A., Chien, L. C., Thomas, S. M., Milliron, K. J., Douglas, J. A, et al. (2010). Absence of CHEK2*1100delC mutation in families with hereditary breast cancer in North America. Cancer Genetics Cytogenetics, 202 (2), 136-140. Abstract retrieved December 13, 2010 from PubMed database.
National Comprehensive Cancer Network. (2010). NCCN clinical practice guidelines in oncologyTM. Genetic/familial high-risk assessment: Breast and ovarian (V.1.2010). Retrieved December 13, 2010 from http://www.nccn.org/professionals/physician_gls/PDF/genetics_screening.pdf. (181 articles and/or guidelines reviewed)
U.S. Preventive Services Task Force. (2005). Genetic risk assessment and BRCA mutation testing for breast and ovarian cancer susceptibility. Retrieved December 13, 2010 from http://www.uspreventiveservicestaskforce.org/uspstf/uspsbrgen.htm. .
ORIGINAL EFFECTIVE DATE: 10/31/1997
MOST RECENT REVIEW DATE: 4/14/2011
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