BlueCross BlueShield of Tennessee Medical Policy Manual

Human Epidermal Receptor Type 2 (HER 2) Testing

DESCRIPTION

HER-2 (human epidermal receptor 2) is a protein receptor found on the surface of certain cancer cells and is associated with more aggressive tumor growth and metastatic activity.  HER2 overexpression is predictive of a good response to anti-HER2 receptor therapy (e.g., trastuzumab, lapatinib, pertuzumab).  Genetic testing is utilized to inform decisions regarding targeted HER2 receptor therapy. 

There are several technologies available for HER2 testing.  The most common test is immunohistochemistry (IHC). Available testing also includes fluorescence in situ hybridization (FISH), chromogenic in situ hybridization (CISH) and silver in situ hybridization (SISH). 

A novel assay has also been explored to quantitatively measure the total HER-2 protein and HER-2 homodimers. HERmark is a proprietary diagnostic that purports to quantify HER-2 protein expression and dimerization in individuals with breast cancer. The HERmark breast cancer assay uses the VeraTag™ methodology.

POLICY

See also: Pertuzumab

IMPORTANT REMINDERS

ADDITIONAL INFORMATION 

Clinical utility of HER-2 genetic testing for any purpose other than breast, gastric, and gastroesophageal cancer has not been demonstrated in well-designed studies. The clinical utility of the HERmark™ assay has not been demonstrated, and clinical trials are needed to determine the impact on health outcomes of individuals stratified by the HERmark assay.

SOURCES  

American Society of Clinical Oncology. (2015). Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: American Society of Clinical Oncology clinical practice guideline. Retrieved July 7, 2016 from the National Guideline Clearinghouse (NGC: 010780).

American Society of Clinical Oncology. (2016). Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer: American Society of Clinical Oncology clinical practice guideline. Retrieved April 13, 2017 from the National Guideline Clearinghouse (NGC: 010957).

BlueCross BlueShield Association. Medical Policy Reference Manual. (12:2015). Quantitative assay for measurement of HER2 total protein expression and HER2 dimers (2.04.76). Retrieved July 6, 2016 from BlueWeb. (18 articles and/or guidelines reviewed)

College of American Pathologists, American Society for Clinical Pathology and American Society of Clinical Oncology. (2016). HER2 testing and clinical decision making in gastroesophageal adenocarcinoma. Retrieved April 13, 2017 from http://ascopubs.org/doi/pdf/10.1200/JCO.2016.69.4836.

Lei, Y., Huang, J., Zhao, Q., Jiang, N., Xu, H., et al. (2017). The clinicopathological parameters and prognostic significance of HER2 expression in gastric cancer patients: a meta-analysis of literature. World Journal of Surgical Oncology, 2017, 15 (68). (Level 1 evidence)

National Comprehensive Cancer Network. (2017). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Breast cancer, V.2.2017. Retrieved April 13, 2017 from https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf.

National Comprehensive Cancer Network. (2017). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Esophageal and esophagogastric junction cancers, V.1.2017. Retrieved April 13, 2017 from https://www.nccn.org/professionals/physician_gls/pdf/esophageal.pdf.

National Comprehensive Cancer Network. (2017). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Gastric cancer, V.1.2017. Retrieved April 13, 2017 from https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf.

National Comprehensive Cancer Network. (2017). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Colon cancer, V.2.2017. Retrieved April 14, 2017 from https://www.nccn.org/professionals/physician_gls/pdf/colon.pdf.

National Comprehensive Cancer Network. (2017). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Rectal cancer, V.3.2017. Retrieved April 14, 2017 from https://www.nccn.org/professionals/physician_gls/pdf/rectal.pdf.

National Comprehensive Cancer Network. (2017). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Non-small cell lung cancer, V.5.2017. Retrieved April 14, 2017 from https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf.

Prendeville, S., Feeley, L., Bennett, M. W., O’Connell, F., & Browne, T. J. (2016). Reflex repeat HER2 testing of grade 3 breast carcinoma at excision using immunohistochemistry and in situ analysis: frequency of HER2 discordance and utility of core needle biopsy parameters to refine case selection. American Journal of Clinical Pathology, 145 (1), 75-80. Abstract retrieved July 7, 2016 from PubMed database.

Pyo, J., Sohn, J., Kim, W. (2016). Concordance rate between HER2 immunohistochemistry and in situ hybridization in gastric carcinoma: systematic review and meta-analysis. The International Journal of Biological Markers, 31 (1), e1-e10. Abstract retrieved April 13, 2017 from PubMed database.

Shan, L., Ying, J., & Lu, N. (2013). HER2 expression and relevant clinicopathological features in gastric and gastroesophageal junction adenocarcinoma in a Chinese population. Diagnostic Pathology, 2013 (8), 76 - 83. (Level 3 evidence - Independent study)

U. S. Food and Drug Administration. (2005, May). Center for Devices and Radiological Health. Pre-market approval decisions for May 2005. P040005. Retrieved April 14, 2017 from https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P040005.

U. S. Food and Drug Administration. (2008, July). Center for Devices and Radiological Health. Pre-market approval decisions for July 2008. P50040. Retrieved April 14, 2017 from https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P050040.

U. S. Food and Drug Administration. (2012). Center for Devices and Radiological Health. Pre-market approval decisions for April 2012. P090015. Retrieved April 14, 2017 from https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpma/pma.cfm?id=P090015.

ORIGINAL EFFECTIVE DATE:  9/1998

MOST RECENT REVIEW DATE:  5/11/2017

ID_BT

Policies included in the Medical Policy Manual are not intended to certify coverage availability. They are medical determinations about a particular technology, service, drug, etc. While a policy or technology may be medically necessary, it could be excluded in a member's benefit plan. Please check with the appropriate claims department to determine if the service in question is a covered service under a particular benefit plan. Use of the Medical Policy Manual is not intended to replace independent medical judgment for treatment of individuals. The content on this Web site is not intended to be a substitute for professional medical advice in any way. Always seek the advice of your physician or other qualified health care provider if you have questions regarding a medical condition or treatment.

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