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A.2.04.63
Several single nucleotide variants (SNVs), which are single base-pair variations in the DNA sequence of the genome, have been found to be associated with breast cancer, are common in the population, but confer only small increases in risk. Commercially available assays test for several SNVs to predict an individual’s risk of breast cancer relative to the general population. Some of these tests incorporate clinical information into risk prediction algorithms. The intent of this type of test is to identify subjects at increased risk who may benefit from more intensive surveillance.
Health Disparities in Breast Cancer
Based on data from 2014 through 2018, age-adjusted breast cancer mortality is approximately 40% higher among Black women compared to non-Hispanic White women in the United States (27.7 vs 20.0 deaths per 100,000 women), despite a lower overall incidence of breast cancer among Black women (125.8 vs 139.2 cases per 100,000 women). Experts postulate that this divergence in mortality may be related to access issues - Black women are more likely than White women to lack health insurance, limiting access to screening and appropriate therapies. Socioeconomic status is also a driver in health and health outcome disparities related to breast cancer. Women with low incomes have significantly lower rates of breast cancer screening, a higher probability of late-stage diagnosis, and are less likely to receive high-quality care, resulting in higher mortality from breast cancer.
Clinical Genetic Tests
GeneType for Breast Cancer
GeneType for Breast Cancer (and the previous versions of the test, BREVAGenplus® and BREVAGen®) evaluates breast cancer-associated single nucleotide variants (SNVs) identified in genome-wide association studies. The first-generation test, BREVAGen, included 7 SNVs. Currently, GeneType includes over 70 SNVs. Risk is calculated by combining individual SNV risks with other risk factors. GeneType has been evaluated for use in African-American, Caucasian, and Hispanic patient samples, age 35 years and older, who do not have a history of in situ or invasive breast cancer and are not carriers of a known pathogenic variant or rearrangement in a breast cancer susceptibility gene.
Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratory-developed tests must meet the general regulatory standards of the Clinical Laboratory Improvement Amendments (CLIA). GeneType for Breast Cancer (Genetic Technologies) is available under the auspices of the CLIA. Laboratories that offer laboratory-developed tests must be licensed by the CLIA for high-complexity testing. To date, the U.S. Food and Drug Administration has chosen not to require any regulatory review of this test.
Germline Genetic Testing for Hereditary Breast/Ovarian Cancer Syndrome and Other High-Risk Cancers (BRCA1, BRCA2, PALB2) is addressed in a separate policy.
Testing for one or more single nucleotide variants to predict an individual’s risk of breast cancer is considered investigational.
The GeneType® breast cancer risk test is considered investigational for all indications, including but not limited to use as a method of estimating individual risk for developing breast cancer.
None
The coverage guidelines outlined in the Medical Policy Manual should not be used in lieu of the Member’s specific benefit plan language.
Genetics Nomenclature Update
The Human Genome Variation Society nomenclature is used to report information on variants found in DNA and serves as an international standard in DNA diagnostics. It is being implemented for genetic testing medical evidence review updates starting in 2017 (see Table 1). The Society's nomenclature is recommended by the Human Variome Project, the Human Genome Organization, and by the Human Genome Variation Society itself.
The American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) standards and guidelines for interpretation of sequence variants represent expert opinion from both organizations, in addition to the College of American Pathologists. These recommendations primarily apply to genetic tests used in clinical laboratories, including genotyping, single genes, panels, exomes, and genomes. Table 2 shows the recommended standard terminology—"pathogenic," "likely pathogenic," "uncertain significance," "likely benign," and "benign"—to describe variants identified that cause Mendelian disorders.
Table 1. Nomenclature to Report on Variants Found in DNA
Previous | Updated | Definition |
Mutation | Disease-associated variant | Disease-associated change in the DNA sequence |
Variant | Change in the DNA sequence | |
Familial variant | Disease-associated variant identified in a proband for use in subsequent targeted genetic testing in first-degree relatives |
Table 2. ACMG-AMP Standards and Guidelines for Variant Classification
Variant Classification | Definition |
Pathogenic | Disease-causing change in the DNA sequence |
Likely pathogenic | Likely disease-causing change in the DNA sequence |
Variant of uncertain significance | Change in DNA sequence with uncertain effects on disease |
Likely benign | Likely benign change in the DNA sequence |
Benign | Benign change in the DNA sequence |
Genetic Counseling
Genetic counseling is primarily aimed at individuals who are at risk for inherited disorders, and experts recommend formal genetic counseling in most cases when genetic testing for an inherited condition is considered. The interpretation of the results of genetic tests and the understanding of risk factors can be very difficult and complex. Therefore, genetic counseling will assist individuals in understanding the possible benefits and harms of genetic testing, including the possible impact of the information on the individual's family. Genetic counseling may alter the utilization of genetic testing substantially and may reduce inappropriate testing. Genetic counseling should be performed by an individual with experience and expertise in genetic medicine and genetic testing methods.
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.
10/13/2009: Policy added.
11/19/2009: Approved by MPAC.
11/17/2010: Policy reviewed; no changes.
10/05/2011: Policy reviewed; no changes.
09/27/2012: Policy reviewed; no changes.
10/22/2013: Policy description updated regarding BREVAGen™. Added BREVAGen™ to the policy statement as investigational. Deleted outdated references from the Sources section. Added CPT code 81479 to the Code Reference section.
10/30/2014: Non-BRCA Breast Cancer Risk Assessment medical policy combined into this policy with new title: "Use of Common Genetic Variants (Single Nucleotide Polymorphisms) to Predict Risk of Nonfamilial Breast Cancer." Policy description updated. Added policy statement that testing for 1 or more single nucleotide polymorphisms (SNPs) to predict an individual’s risk of breast cancer is considered investigational. Policy statement updated to state that the OncoVue® and BREVAGen™ tests are considered investigational for all indications.
07/23/2015: Code Reference section updated for ICD-10.
03/03/2016: Policy description updated regarding SNP panel tests and clinical genetic tests. Policy statement updated to change "BREVAGen" to "BREVAGenplus®." Investigative definition updated in policy guidelines section. Deleted outdated reference from the Sources section.
06/06/2016: Policy number A.2.04.63 added.
10/26/2017: Removed OncoVue from the policy as it is no longer commercially available. Policy description updated regarding genetic tests and to change "single nucleotide polymorphisms" to "single nucleotide variants." First investigational statement updated to change "polymorphisms" to "variants." Second investigational statement updated to remove "OncoVue." Policy Guidelines updated regarding genetics nomenclature and genetic counseling.
10/29/2018: Policy description updated. Policy statements unchanged.
11/15/2019: Policy description updated to remove section regarding gene variants and breast cancer risk. Policy statements unchanged. Policy Guidelines updated.
11/19/2020: Policy reviewed; no changes.
06/23/2022: Policy description updated regarding clinical genetic tests. Second policy statement updated to change "BREVAGenplus" to "GeneType®." Policy Guidelines updated regarding genetic counseling.
08/15/2022: Code Reference section updated to add CPT code 81599.
12/08/2022: Policy description updated regarding health disparities in breast cancer. Policy statement updated to remove "patient." Policy Guidelines updated to change "patients" to "individuals."
11/13/2023: Policy reviewed; no changes.
01/08/2025: Policy reviewed; no changes.
Blue Cross Blue Shield Association Policy # 2.04.63
This may not be a comprehensive list of procedure codes applicable to this policy.
Code Number | Description |
CPT-4 | |
81479 | Unlisted molecular pathology procedure |
81599 | Unlisted multianalyte assay with algorithmic analysis |
HCPCS | |
ICD-10 Procedure | |
ICD-10 Diagnosis |
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