Gene Expression Profiling Assays as a Technique to Determine Prognosis for Managing Breast Cancer Treatment
DESCRIPTION
Breast cancer prognosis is currently based on individual age, tumor size, histology, status of the axillary lymph nodes, histologic type, and hormone receptor status. Individuals with the same set of risk factors can have markedly different prognoses and varied courses of treatment.
There is currently an interest in examining gene expression in tumor tissue as a prognostic factor for cancer recurrence and for managing breast cancer treatment. As opposed to genetic tests, which measure an individual's inherited genetic makeup and are utilized to estimate the risk of developing a disease (e.g., cancer), the gene-profiling assay measures the expression of genes within an individual's cancerous tumor. For example, RNA (ribonucleic acid) can be isolated from tumor tissue and used to generate complementary RNA. It is then labeled and allowed to hybridize to microarrays that can contain up to 25,000 human genes. Positive results are detected by fluorescent intensities. Patterns of the gene expression can then be compared to outcome databases to identify specific patterns that may be associated with prognosis. It is believed this information may then be used to predict an individual's likelihood of cancer recurrence, and in the clinical decision-making process regarding the use of adjuvant chemotherapy and/or optional chemotherapy regimen.
Examples of these assays include: Oncotype DX™ (21-gene panel); MammaPrint® (70-gene panel; also referred to as the "Amsterdam signature"); Mammostrat™ (Applied Genomics Inc.), the Molecular Grade Index (Aviara MGISM, AviaraDX, Inc.) and THEROS Breast Cancer IndexSM.
POLICY
The use of the 21-gene RT-PCR assay (i.e., Oncotype DX) to determine recurrence risk for women deciding whether or not to undergo adjuvant chemotherapy for the treatment of breast cancer is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
The use of the 21-gene RT-PCR assay (i.e., Oncotype DX) for any other indications, including determination of recurrent risk in breast cancer in individuals who are lymph node-positive, is considered investigational.
The use of other gene expression assays for the treatment of breast cancer (e.g., MammaPrint, Mammostrat, or the THEROS Breast Cancer IndexSM) is considered investigational.
MEDICAL APPROPRIATENESS
The use of the 21-gene RT-PCR assay (i.e., Oncotype DX) to determine recurrence risk for women deciding whether or not to undergo adjuvant chemotherapy for the treatment of breast cancer is considered medically appropriate if ALL of the following criteria are met:
The breast cancer is primary
Unilateral, non-fixed tumor
Tumor size 0.6-1cm (non-fixed) with moderate/poor differentiation or unfavorable features, OR tumor size greater than 1cm
Estrogen-receptor (ER) positive or progesterone-receptor (PR) positive
Tumor HER2-negative
Node-negative
Individual will be treated with adjuvant endocrine therapy (e.g., tamoxifen or aromatase inhibitors)
The test will aid the individual in making the decision regarding chemotherapy (i.e., when chemotherapy is a therapeutic option)
Oncotype DX must be ordered within six months following diagnosis
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
There is inadequate scientific evidence to permit conclusions regarding the use of MammaPrint® and the Breast Cancer Gene Expression Ratio as risk assessment tools in predicting tumor recurrence.
When an individual has multiple ipsilateral primaries, a specimen from the tumor with the most aggressive histological characteristics should be submitted for testing, as this is how prognosis is clinically determined. It is not necessary to conduct Oncotype DX testing on each tumor.
SOURCES
Agency for Healthcare Research and Quality. (2008, January). Evidence report/technology assessment No. 160: Impact of gene expression profiling tests on breast cancer outcomes. (DHHS AHRQ Publication No. 08-E002). Retrieved January 25, 2008 from http://www.ahrq.gov.
BlueCross BlueShield Association. Medical Policy Reference Manual. (11:2009). Assays of genetic expression in tumor tissue as a technique to determine prognosis in patients with breast cancer (2.04.36). Retrieved January 7, 2010 from BlueWeb. (36 articles and/or guidelines reviewed)
ECRI Institute. Health Technology Information Service. Emerging Technology (TARGET) Evidence Report. (2008, January). Gene expression profiling of breast cancer to predict the likelihood of recurrence. Retrieved December 21, 2009 from ECRI Institute. (22 articles and/or guidelines reviewed)
Evaluation of Genomic Applications in Practice and Prevention. (2009). Recommendations from the EGAPP working group: can tumor gene expression profiling improve outcomes in patients with breast cancer? Genetics in Medicine, 11 (1), 66-73.
Harris, L., Fritsche, H., Mennel, R., Norton, L., Ravdin, P., Taube, S., et al. (2007). American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. Journal of Clinical Oncology, 25 (33), 1-26.
National Comprehensive Cancer Network. (2010, January). NCCN clinical practice guidelines in oncology™. Breast Cancer. (V.1.2010). Retrieved January 15, 2010 from http://www.nccn.org/professionals/physician_gls/PDF/breast.pdf.
Oakman, C., Bessi, S., Zafarana, E., Galardi, F., Biganzoli, L., & Di Leo, A. (2009). Recent advances in systematic therapy: New diagnostics and biological predictors of outcome in early breast cancer. Breast Cancer Research, 11 (2), 250. Retrieved January 25, 2010 from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2688942/pdf/bcr2238.pdf. (Level 5 Evidence - Review)
Technology Evaluation Center. (2008, April). Gene expression profiling of breast cancer to select women for adjuvant chemotherapy. (Vol. 22, No. 13). Chicago: BlueCross BlueShield Association. (94 articles and/or guidelines reviewed)
U. S. Food and Drug Administration. (2007, February). Center for Devices and Radiological Health. 510(k) Pre-Market Notification Database. K062694. Retrieved October 10, 2007 from http://www.fda.gov/cdrh/reviews/K062694.pdf.
U. S. Food and Drug Administration. (2007, May). Center for Devices and Radiological Health. Guidance for industry and FDA staff. Class II special controls guidance document: Gene expression profiling test system for breast cancer prognosis. Retrieved January 25, 2008 from http://www.fda.gov/cdrh/oivd/guidence/1627.html.
ORIGINAL EFFECTIVE DATE: 10/13/2005
MOST RECENT REVIEW DATE: 3/8/2012
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