DESCRIPTION
Several single-nucleotide polymorphisms (SNPs), which are single base-pair variations in the DNA sequence of the genome, have been found to be associated with breast cancer and are common in the population, but confer only small increases in risk. Some commercially available assays test for several SNPs and combine results to predict an individual’s risk of breast cancer relative to the general population in order to identify those at increased risk who might benefit from more intensive surveillance.
Rare, single gene variants conferring a high risk of breast cancer have been linked to hereditary breast cancer syndromes. Examples are mutations in BRCA1 and BRCA2. These, and a few others, account for less than 25% of inherited breast cancer. Moderate risk alleles, such as variants in the CHEK2 gene, are also relatively rare and apparently explain very little more of the genetic risk.
In contrast, several common SNPs associated with breast cancer have been identified primarily through genome-wide association studies of very large case-control populations. The high-risk alleles occur with high frequency in the general population, although the increased breast cancer risk associated with each is very small relative to the general population risk. Some have suggested that these common risk SNPs could be combined to achieve an individualized risk prediction either alone or in combination with traditional predictors in order to personalize screening programs in which starting age and intensity would vary by risk.
Various companies now offer such SNP-derived risk estimates. For example, deCODE (Reykjavik, Iceland) offers the deCODE BreastCancer™ test, based on a panel of 7 SNPs identified primarily in genome-wide association studies. 23andMe (Mountain View, California) offers direct-to-consumer (DTC) testing which includes 3 SNPs in known genes in their “Health Edition” test: 2 detect common polymorphisms in BRCA1 and BRCA2 genes associated with hereditary breast cancer in Ashkenazi Jewish populations, and one that detects a CHEK2 moderate risk variant. Navigenics (Foster City, CA) includes information on breast cancer risk in their overall DTC comprehensive genetic testing panel but does not appear to identify the individual SNPs used in their panel on their website.
POLICY
Testing for one or more single nucleotide polymorphisms (SNPs) to predict an individual’s risk of breast cancer is considered investigational.
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ADDITIONAL INFORMATION
Studies are not available that provide direct evidence of the clinical outcomes (clinical utility) of testing for one or more single nucleotide polymorphisms (SNPs) to predict an individual’s risk of breast cancer and how this would affect direct patient management. The application of such risk panels to individual patient management or to population screening programs is premature due to the expectation that the majority of the genetic risk of breast cancer has yet to be explained by undiscovered gene variants and SNPs, and thus the discrimination offered by the limited genetic factors currently known is insufficient to inform clinical practice.
Tests combining the results of SNPs to predict breast cancer risk are available either as a laboratory-developed service by physician order from a clinical laboratory licensed for high complexity testing under the Clinical Laboratory Improvement Amendments (CLIA); or as a DTC laboratory-developed service. In the latter case, it is not clear that the laboratory is necessarily CLIA-licensed although some states have chosen to regulate DTC laboratories in the same way as clinical laboratories (e.g., New York state). None of these tests have been cleared by the U.S. Food and Drug Administration. As examples, but not inclusive of all available services, The deCODE BreastCancer™ test requires a physician order (however, the deCODEme Cancer Scan, which includes a breast cancer risk estimate, does not); 23andme and Navigenics accept direct consumer test orders; and all three companies either contract with or operate CLIA-licensed laboratories to do their genetic testing. The companies themselves mathematically combine single marker results into risk estimates and provide interpretations.
SOURCES
BlueCross BlueShield Association. Medical Policy Reference Manual. (4:2010). Use of common genetic variants to predict risk of nonfamilial breast cancer (2.04.63). Retrieved July 8, 2010 from BlueWeb. (20 articles and/or guidelines reviewed)
Pharoah, P., Antoniou, A., Easton, D., & Ponder, B. (2008). Polygenes, risk prediction, and targeted prevention of breast cancer. New England Journal of Medicine, 358 (26), 2796-2803.
Wacholder, S., Hartge, P., Prentice, R., Garcia-Closas, M., Feigelson, H.,Diver, W., et al. (2010). Performance of common genetic variants in breast-cancer risk models. New England Journal of Medicine, 362 (11), 986-993.
ORIGINAL EFFECTIVE DATE: 12/11/2010
MOST RECENT REVIEW DATE: 12/11/2010
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