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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. Other cancers, such as prostate cancer, pancreatic cancer, gastrointestinal cancers, melanoma, laryngeal cancer, occur more frequently in HBOC families. 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.
Genetic testing for BRCA1 and BRCA2 mutations in cancer-affected individuals may be considered medically necessary under any of the following circumstances:
Genetic testing for BRCA1 and BRCA2 mutations of unaffected adults may be considered medically necessary under any of the following circumstances:
Further, the genetic testing should be performed in a setting that has suitably trained healthcare providers who can give appropriate pre- and post-test counseling and that has access to a CLIA-licensed laboratory that offers comprehensive mutation analysis (see Policy Guidelines).
Testing for genomic rearrangements of the BRCA1 and BRCA2 genes may be considered medically necessary in patients who meet criteria for BRCA testing, whose testing for point mutations is negative.
Unless they meet the criteria above, genetic testing for either those affected with breast, ovarian, fallopian tube, or primary peritoneal cancer or for unaffected individuals, including those with a family history of pancreatic cancer, is considered investigational.
Testing for CHEK2 abnormality (mutations, deletions, etc.) is considered investigational in affected and unaffected patients with breast cancer, irrespective of the family history.
Genetic testing in minors for BRCA1 and BRCA2 mutations is investigational.
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member's specific benefit plan language.
Medically Necessary is defined as those services, treatments, procedures, equipment, drugs, devices, items or supplies furnished by a covered Provider that are required to identify or treat a Member's illness, injury or Nervous/Mental Conditions, and which Company determines are covered under this Benefit Plan based on the criteria as follows in A through D:
A. consistent with the symptoms or diagnosis and treatment of the Member's condition, illness, or injury; and
B. appropriate with regard to standards of good medical practice; and
C. not solely for the convenience of the Member, his or her Provider; and
D. the most appropriate supply or level of care which can safely be provided to Member. When applied to the care of an Inpatient, it further means that services for the Member's medical symptoms or conditions require that the services cannot be safely provided to the Member as an Outpatient.
For the definition of Medically Necessary, “standards of good medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. BCBSMS makes no payment for services, treatments, procedures, equipment, drugs, devices, items or supplies which are not documented to be Medically Necessary. The fact that a Physician or other Provider has prescribed, ordered, recommended, or approved a service or supply does not in itself, make it Medically Necessary.
Investigative is defined as the use of any treatment procedure, facility, equipment, drug, device, or supply not yet recognized as a generally accepted standard of good medical practice for the treatment of the condition being treated and; therefore, is not considered medically necessary. For the definition of Investigative, “generally accepted standards of medical practice” means standards that are based on credible scientific evidence published in peer-reviewed medical literature generally recognized by the relevant medical community, and physician specialty society recommendations, and the views of medical practitioners practicing in relevant clinical areas and any other relevant factors. In order for equipment, devices, drugs or supplies [i.e, technologies], to be considered not investigative, the technology must have final approval from the appropriate governmental bodies, and scientific evidence must permit conclusions concerning the effect of the technology on health outcomes, and the technology must improve the net health outcome, and the technology must be as beneficial as any established alternative and the improvement must be attainable outside the testing/investigational setting.
In identifying families with a high risk of mutation in the BRCA1 or BRCA 2 gene, both maternal and paternal family histories are important, but each lineage must be considered separately. Any of the following scenarios indicates a high risk of BRCA1 or BRCA2 mutation. In assessing risk of a mutation for those affected with cancer, the overall family history (one lineage) including the affected person is considered. The following criteria for non-Ashkenazi Jewish women unaffected with cancer were derived by the USPSTF in 2005 after extensive literature review by the U.S. Preventive Services Task Force (USPSTF):
More recent definitions of high-risk have been published, including the 2011 revised recommendations from National Comprehensive Cancer Network (NCCN). The following high-risk criteria largely represent NCCN hereditary breast and/or ovarian cancer syndrome testing criteria with some modifications based on additional guidelines and review of evidence.
A personal or family history suggesting genetic cancer susceptibility requires at least one of the following criteria to be present:
Early age at diagnosis refers generally to diagnosis before age 40 to 45 years; an exact cutoff for testing affected individuals without known family history but with cancer diagnosis at an early age has not been established, although guidelines of the American College of Medical Genetics suggest age 45 or younger (see Rationale). The decision to test an affected individual based on age at diagnosis in the absence of family history will depend on the risk estimate for the individual patient (e.g., from widely available risk assessment computer programs) and the patient tolerance for risk, and the desire to inform the risk of family members.
Definition: Close blood relative typically refers to first degree (parent, full sibling, or offspring) and second degree (grandparent, grandchild, uncle, aunt, niece, nephew, or half-sibling) relatives in diseases associated with high penetrance gene mutations such as BRCA1 and BRCA2 mutations. Accommodation may be made to include third degree relatives (first cousin, great grandparent or great grandchild) in some cases, e.g., limited family history, particularly in tracing hereditary breast and ovarian and related cancers in the paternal lineage. Certified genetic counselors or other qualified genetics professionals are best able to assess exceptional cases.
As the majority of test results will be negative and uninformative in unaffected family members of potential BRCA mutation families, it is strongly recommended that an affected family member be tested first whenever possible to adequately interpret the test. Should a BRCA mutation be found in an affected family member(s), 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. Interpreting the test results for an unaffected family member without knowing the genetic status of the family may be possible in the case of a positive result for an established disease-associated mutation but leads to difficulties in interpreting negative test results or mutations of uncertain significance because the possibility of a causative BRCA mutation is not ruled out.
In patients with breast cancer, ovarian cancer, cancer of the fallopian tube, or primary peritoneal cancer who are from high-risk families without a known BRCA1 or BRCA2 gene and who are not from ethnic groups with known founder mutations, comprehensive BRCA mutation analysis should be performed.
Testing in eligible individuals who belong to ethnic populations in which there are well-characterized founder mutations should begin with tests specifically for these mutations. For example, founder mutations account for approximately three quarters of the BRCA mutations found in Ashkenazi Jewish populations (see Rationale). When the testing for founder mutations is negative, comprehensive mutation analysis should then be performed.
Comprehensive mutation analysis currently includes sequencing the coding regions and intron/exon splice sites, as well as tests to detect common large deletions and rearrangements that can be missed with sequence analysis alone. However, current routine laboratory testing for genomic rearrangement is more limited than the criteria noted in the policy statement; automatic testing is specified for those with a risk of BRCA mutation of at least 30%. In addition, prior to August 2006, testing for large deletions and rearrangements was not performed, thus some patients with familial breast cancer who had negative BRCA testing prior to this time may consider repeat testing for the rearrangements (see Policy statement for criteria). These rates are calculated using the Myriad II risk model (Available online at: www.myriadtests.com).
As noted above, cancers of the fallopian tube and primary peritoneal cancer are also considered BRCA-associated malignancies and are to be considered along with breast and ovarian cancer in assessing the family history.
POLICY HISTORY2/2001: Approved by Medical Policy Advisory Committee (MPAC)
2/12/2002: Investigational definition added
3/8/2002: Case-by-case consideration deleted
5/1/2002: Type of Service and Place of Service deleted.
5/14/2002: Code Reference section updated; ICD-9 diagnosis codes V10.3 and V10.43 deleted
1/30/2003: Medically necessary verbiage added to "Policy" section
6/12/2003: Code Reference section updated
7/2003: Reviewed by MPAC, "Genetic counseling is required by a board certified geneticist." deleted, minors age changed to 18Code Reference section updated, CPT code range 83890-83906 listed separately, ICD-9 diagnosis code range 174.0-174.9, 175.0-175.9 listed separately, FEP exception added
7/30/2004: Code Reference section updated, ICD-9 diagnosis code V10.3, V10.43 added
11/11/2005: Code Reference section updated, 5th digit added to ICD9 diagnosis code V26.31, description revised
3/28/2006: Coding updated. CPT4/HCPCS 2006 revisions added to policy.
9/12/2006: Coding updated. ICD9 2006 revisions added to policy.
12/28/2006: Code Reference section updated per the 2007 CPT/HCPCS revisions
7/20/2007: Policy reviewed. Genetic testing for individuals with early onset breast or ovarian cancer without a known family history, and unaffected individuals from families with a high risk of BRCA1 or BRCA2 mutation based on family history where it is not possible to test an affected member added as may be medically necessary. Genetic testing of unaffected individuals of potentially high-risk populations (e.g. Ashkenazi Jewish descent) changed from investigational to may be medically necessary. HCPCS S3823 moved to covered. Non-covered codes table removed. FEP exceptions removed
9/12/2007: Code reference section updated per the annual ICD-9 updates effective 10-1-2007
12/19/2007: Coding updated per the 2008 CPT/HCPCS revisions
2/26/2008: Policy description updated. Policy statements revised. Added genetic testing of cancer affected women with breast or ovarian cancer with no family history, women affected with both breast and ovarian cancer, men affected with breast cancer at any age maybe medically necessary in cancer-affected individuals. Policy statements clarified for cancer-affected and unaffected individuals from a high risk ethnic background (Ashkenazi Jewish descent). Clarified investigational policy statement for genetic testing in unaffected individuals and those not meeting policy criteria. Policy title changed from "Genetic Testing for Inherited BRCA1 or BRCA2 Mutations" to "Genetic Testing for Hereditary Breast and/or Ovarian Cancer"
12/24/2008: Coding Reference section updated per 2009 CPT/HCPCS revisions
2/3/2009: Policy statement and policy guideline section updated.
07/30/2010: Policy Description section was revised to add fallopian tube and primary peritoneal cancers. Information about CHEK2 was also added. Policy Statement section was revise to add fallopian tube or primary peritoneal cancers and testing for CHEK2 genetic abnormalities (mutations, deletions, etc.) is considered investigational in affected and unaffected patients with breast cancer irrespective of the family history. Policy Guidelines section was revised to add fallopian tube and primary peritoneal cancers. CPT codes 88271 - 88275 and 88291 were added to the Covered Codes Table. ICD-9 Diagnosis code 233.3 was removed from table (deleted 9-30-2007) and 233.39 was added to Covered Codes Table; however, V26.35 was removed from the Covered Codes Table.
02/24/2012: Policy statement regarding CHEK2 revised to state the following: Testing for mutations other than BRCA1 and BRCA2, such as the CHEK2 abnormality (mutations, deletions, etc.) is considered investigational in affected and unaffected patients with breast cancer irrespective of the family history. It previously stated the following: Testing for CHEK2 genetic abnormalities (mutations, deletions, etc.) is considered investigational in affected and unaffected patients with breast cancer irrespective of the family history. Deleted outdated references from the Sources section.
07/19/2012: The second bullet in the first policy statment was re-written. Added the following medically necessary policy statement: Testing for genomic rearrangements of the BRCA1 and BRCA2 genes may be considered medically necessary in patients who meet criteria for BRCA testing, whose testing for point mutations is negative and either (1) there are 3 or more family members (one lineage) affected with breast or ovarian or fallopian tube or primary peritoneal cancer or (2) who have a risk of a BRCA mutation of at least 10%. Updated the policy guidelines regarding high risk criteria. Added CPT codes 81211 - 81217 to the Code Reference section.
02/20/2013: Policy statement regarding coverage of testing for epithelial ovarian/fallopian tube/primary peritoneal cancer clarified. Additional medical necessary statement for testing added for women with breast cancer and two or more close relatives with pancreatic cancer. The policy statement regarding testing for genomic rearrangements was revised to delete the following requirements: and either (1) there are 3 or more family members (one lineage) affected with breast or ovarian or fallopian tube or primary peritoneal cancer or (2) who have a risk of a BRCA mutation of at least 10%.
04/07/2014: Policy statement updated to add "including those with a family history of pancreatic cancer" to the investigational statement. Removed deleted CPT Codes 83890 - 83894, 83896 - 83898, 83900 - 83909, and 83912 - 83914 from the Code Reference section.
08/28/2015: Medical policy revised to add ICD-10 codes. Removed ICD-9 procedure code 99.99 from the Code Reference section. Removed the following deleted HCPCS codes: S3818, S3819, S3820, S3822, and S3823.
12/31/2015: Policy guidelines updated to add medically necessary and investigative definitions. Code Reference section updated to add new 2016 CPT code 81162.
06/08/2016: Policy number added.
SOURCE(S)Blue Cross Blue Shield Association policy # 2.04.02
CODE REFERENCEThis may not be a comprehensive list of procedure codes applicable to this policy.
The code(s) listed below are ONLY medically necessary if the procedure is performed according to the "Policy" section of this document.