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Several genetic cancer syndromes with an autosomal dominant pattern of inheritance associated with an increased risk of breast or ovarian cancer have been identified. Genes included in this policy are those associated with hereditary breast and/or ovarian cancer syndromes that have been shown to have high penetrance, meaning that a large proportion of individuals with certain mutations in the gene will develop the disorder.

Genetic testing for cancer susceptibility may be approached by a focused method that involves testing for well-characterized mutations based on a clinical suspicion of which gene(s) may be the cause of the familial cancer. Panel testing involves testing for multiple mutations in multiple genes at one time.

Several companies offer genetic testing panels for assessing risk of hereditary cancers that use next generation sequencing methods. Next generation sequencing refers to one of several methods that use massively parallel platforms to allow the sequencing of large numbers of DNA segments. Panel testing is potentially associated with greater efficiencies in evaluating genetic diseases; however, it may provide information on genetic variants of unclear clinical significance or which would not lead to changes in patient management.

FDA approval is not currently required for these genetic tests. Clinical laboratories may develop and validate tests in-house ("home-brew") and market them as a laboratory service. The laboratory offering the service must be licensed by Clinical Laboratory Improvement Amendments (CLIA) for high-complexity testing.

Genetic Counseling

Determining the appropriateness of genetic testing for a particular individual can be complex due to the many personal and family history factors that must be taken into consideration to determine which, if any, test is appropriate. Interpretation of test results and discussion of the possible health implications for the patient and family members are also important considerations. 

Pharmacogenetic testing to aid in identifying targeted therapies for breast or ovarian cancers is not addressed in this policy. Please refer to policy VI-49: Expanded Molecular Panel Testing of Cancers to Identify Targeted Therapies.

Definitions

Close Blood Relative:  for the purposes of this policy, a relative is someone who is related by blood; a first-, second-, or third-degree relative from the same side of the family.

• First degree relative:  A family member who shares about 50 percent of their genes with a particular individual in a family. First degree relatives include parents, offspring, and siblings.
• Second degree relative:  A family member who shares about 25 percent of their genes with a particular individual in a family. Second degree relatives include grandparents, grandchildren, uncles, aunts, nephews, nieces, and half-siblings.
• Third degree relative:  A family member who shares about one-eighth of their genes, such as first cousins, great-grandparents, great-aunts, great-uncles.

Gleason score is the preferred system for histopathological grading of prostate cancer. The score reflects the differentiation of cells in primary and secondary patterns. The combined scores from each pattern may range from 2-10. A Gleason score of 7 indicates a moderately aggressive tumor with intermediate differentiation. A score of 8 or greater indicates poorly differentiated or undifferentiated cells and a more aggressive tumor.

Note:  Panel testing for risk of other hereditary cancer syndromes is addressed in policy VI-56: Genetic Cancer Susceptibility Panels.

I.  Genetic Counseling

Genetic testing for hereditary breast and/or ovarian cancer may be considered MEDICALLY NECESSARY and APPROPRIATE when ALL of the following criteria for genetic counseling are met along with criteria in sections II, IV, or V below:

• A recommendation for testing is confirmed by ONE of the following:
  • A physician who is certified by the American Board of Medical Genetics and Genomics or has active candidate status for certification who has no financial relationship with the testing laboratory*;
  • An American Board of Medical Genetics and Genomics or American Board of Genetic Counseling certified or certification eligible Genetic Counselor who has no financial relationship with the testing laboratory*;
  • A nurse credentialed as either a Genetic Clinical Nurse (GCN) or an Advanced Practice Nurse in Genetics (APNG) by either the Genetic Nursing Credentialing Commission (GNCC) or the American Nurses Credentialing Center (ANCC) who has no financial relationship with the testing laboratory*;
  • A surgeon or oncologist who is trained in the treatment of breast, ovarian, fallopian tube, primary peritoneal, pancreatic, or prostate cancer who has no financial relationship with the testing laboratory*; 
• AND
• Content of counseling includes BOTH of the following:
  • Evaluation of a 3-generation pedigree; and
  • Discussion of ALL of the following with the individual who is considering testing:
    • When clinically appropriate, options for surveillance and risk reduction (e.g., lifestyle, chemoprevention, risk-reducing surgery) for individuals with positive results, individuals with negative results, and key differences between the two; and
    • Potential for uninformative or uncertain test results; and
    • Potential physical and emotional risks associated with the test results; and
    • Potential that test results may provide health information regarding the risk of disease for other family members.

*Genetics professionals are not excluded if they are employed by or contracted with a laboratory that is part of an Integrated Health System which routinely delivers health care services beyond just the laboratory test itself.

II.  Known Familial Mutation

Single-site (known familial variant) analysis of BRCA1 and/or BRCA2 may be considered MEDICALLY NECESSARY AND APPROPRIATE for an individual who meets ALL of the following:

• Genetic counseling criteria in section I have been met; AND
• Known familial mutation in BRCA1 and or BRCA2 identified in 1st, 2nd, or 3rd degree relative(s); AND
• No previous germline BRCA1 and/or BRCA2 testing or results of previous testing were incomplete..

III.  Personal History of Cancer

Genetic testing of BRCA1 and/or BRCA2 may be considered MEDICALLY NECESSARY AND APPROPRIATE for an individual who meets ALL of the following:

• Testing recommended by the treating surgeon or oncologist; AND
• Personal history of one or more of the following at any age:
  • Breast cancer
  • Ovarian cancer
  • Fallopian tube cancer
  • Primary peritoneal cancer
  • Pancreatic cancer
  • Prostate cancer that meets at least one of the following:
    1. Metastatic or intraductal ; or
    2. High-grade (Gleason score of 7 or greater) at any age meeting one or both of the following:
       • Ashkenazi Jewish ancestry; or
       • One or more close blood relative(s) with breast cancer age ≤ 50 years, ovarian cancer, pancreatic cancer, metastatic or intraductal prostate cancer at any age; or
       • Two or more close blood relatives with breast or prostate cancer at any age;
  • Tumor profiling of any tumor type in the absence of  germline variant analysis detects BRCA1 and/or BRCA2 pathogenic/likely pathogenic variant; 
• AND
• No previous germline BRCA1 and/or BRCA2 testing; or results of previous testing were incomplete. 

IV.  Predisposition Testing in Individuals with No Personal History of Cancers in Section III

Genetic testing of BRCA1 and/or BRCA2 may be considered MEDICALLY NECESSARY AND APPROPRIATE for an individual with no personal history of cancers listed in section III of this policy who meets ALL of the following:

• Genetic counseling criteria in section I have been met; AND
• A first-or second-degree blood relative meets any of the criteria in section III of this policy; AND
• Has a reasonable likelihood of a mutation based on pre-test genetic counseling; AND
• Unaffected member is the most informative person to test. All affected family members are deceased, or all affected family members have been contacted and are unwilling to be tested; AND
• No previous germline BRCA1 and/or BRCA2 testing; or results of previous testing were incomplete. 

V.  Multi-Gene Panel Sequencing

Genetic testing for hereditary breast and/or ovarian cancer using a multi-gene sequencing panel that includes BRCA1/BRCA2 genes is considered MEDICALLY NECESSARY AND APPROPRIATE when an individual meets ALL of the following:

• Genetic counseling meeting criteria in section I documents a family history/pedigree demonstrating a reasonable likelihood for one of the following cancer syndromes (associated genes in parentheses):
  • Bannayan-Riley-Ruvalcaba syndromes, Cowden syndrome, PTEN hamartoma syndrome (PTEN)
  • Hereditary diffuse gastric cancer syndrome (CDH1)
  • Li Fraumeni syndrome (TP53)
  • Lynch syndrome/hereditary non-polyposis colorectal cancer (MSH2, MLH1, MSH6, MUYH, PMS2, PMS1, EPCAM)
  • PALB2 genetic mutation associated with increased risk of breast cancer (PALB2)
  • Peutz-Jeghers syndrome (STK11) 
• AND
• Unaffected member is the most informative person to test. All affected family members are deceased, or all affected family members have been contacted and are unwilling to be tested; AND
• The panel is limited to genes that have proven utility for clinical management of hereditary breast and/or ovarian cancer; AND
• Results of testing will impact the medical management of the individual (e.g., increased screening or surveillance).

VI.  Experimental/Investigative

Genetic testing for hereditary breast and/or ovarian cancer as either a single-gene or multi-gene panel test is considered EXPERIMENTAL/INVESTIGATIVE for all other indications including but not limited to the following due to a lack of clinical evidence demonstrating an effect on health outcomes:

• Testing will not affect treatment or surveillance decisions
• Testing offered as a direct access (also known as direct to consumer)
• Testing in the general population as a screening tool
• All other testing for risk of hereditary breast and/or ovarian cancer that do not meet criteria as stated above.

Documentation Submission

Documentation from the ordering clinician supporting the medical necessity criteria in the policy must be included in the prior authorization. In addition, the following documentation must be submitted:

• Documentation from the clinical notes that criteria for genetic counseling (if required) have been met, AND
• Documentation of one of the following:
  • Known deleterious mutation in genes addressed in this policy in a close blood relative; OR
  • Diagnosis of individual with personal history of cancers addressed in this policy; OR
  • Results of pedigree indicating need for testing in individual with family history only; OR
  • Results of pedigree and genes for which multigene panel testing is indicated

Link to Pre-Authorization Form:  https://www.bluecrossmn.com/sites/default/files/DAM/2019-10/X18509R07_Pre-Authorization%20Request%20Form.pdf