BlueCross BlueShield of Tennessee Medical Policy Manual

Breast Cancer Gene Expression Assays


Laboratory tests have been developed that detect the expression of many different genes in breast tumor tissue and combine the results into a prediction of distant recurrence risk (return of detectable cancer in another part of the body) for women with early-stage breast cancer.  Test results may help determine whether to include adjuvant chemotherapy in post-surgical management of breast cancer.

For women with early-stage invasive breast cancer considering adjuvant chemotherapy who receive gene expression profiling using one of the assays listed below, a low score is associated with a low risk of recurrence.


Test Manufacturer Description
Oncotype DX® Genomic Health 21-gene RT-PCR (reverse transcriptase-polymerase chain reaction)
EndoPredict Sividon Diagnostics 12-gene real-time RT-PCR (reverse transcriptase-polymerase chain reaction)
Breast Cancer Index SM bioTheranostics Combines molecular grade index and the HOXB13:IL17BR Index using RT-PCR
Prosigna NanoString Technologies nCounter® digital analysis system based on prediction analysis of microarray (PAM) 50 breast cancer intrinsic subtype classifier





Tests intended to assess estrogen receptor, progesterone receptor and HER2 status, such as TargetPrint®, and tests that do not provide a specific recurrence risk are outside the scope of this policy. 


American Society of Clinical Oncology. (2017). Use of biomarkers to guide decisions on adjuvant systemic therapy for women with early-stage invasive breast cancer. Retrieved January 16, 2018 from

Blok, E.J., Bastiaannet, E., van den Hout, W.B., Liefers, G.J., Smit, V.T., Kroep, J.,R., & van de Velde, C.J.H. (2018). Systematic review of the clinical and economic value of gene expression profiles for invasive early breast cancer available in Europe. Cancer Treatment Reviews, 62, 74-90. (Level 1 evidence)

BlueCross BlueShield Association. Medical Policy Reference Manual. (11:2017). Assays of genetic expression in tumor tissue as a technique to determine prognosis in patients with breast cancer (2.04.36). Retrieved January 12, 2018 from BlueWeb. (71 articles and/or guidelines reviewed)

Cardosa, F., van’t Veer, L.J., Bogaerts, J., Slaets, L., Viale, G., Delaloge, S., et al. (2016). 70-gene signature as an aid to treatment decisions in early-stage breast cancer. New England Journal of Medicine, 375 (8), 717-729. (Level 1 evidence)

Dubsky, P., Brase, J., Jakesz, R., Rudas, M., Singer, C., Greil, R., et al. (2013). The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients. British Journal of Cancer, 109, 2959-2964. (Level 2 evidence)

Müller, B., Keil, E., Lehmann, A., Winzer, K., Richter-Ehrenstein, C., Prinzler, J., et al. (2013). The EndoPredict gene expression assay in clinical practice - performance and impact on clinical decisions. PLOS One, 8 (6), e68252. (Level 4 evidence)

National Comprehensive Cancer Network. (2017). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Breast cancer. Version 3.2017. Retrieved January 12, 2018 from the National Comprehensive Cancer Network.

National Institute for Health and Care Excellence. (2013). Gene expression profiling and expanded immunohistochemistry tests for guiding adjuvant chemotherapy decisions in early breast cancer management: MammaPrint, Oncotype DX, IHC4 and Mammostrat. Retrieved January 6, 2017 from

Palmetto Government Benefit Administrators. (2018, February). LCD for Breast cancer index genetic assay. (L35631). Retrieved January 17, 2018 from

Palmetto Government Benefit Administrators. (2018, February). LCD for EndoPredict breast cancer gene expression test. (L37264). Retrieved January 17, 2018 from

Palmetto Government Benefit Administrators. (2018, February). LCD for Oncotype DX breast Cancer for DCIS (Genomic Health). (L36912). Retrieved January 17, 2018 from

Palmetto Government Benefit Administrators. (2018, February). LCD for Breast cancer assay: Prosigna. (L36125). Retrieved January 17, 2018 from

Sgroi, D., Sestak, I., Cuzick, J., Zhang, Y., Schnabel, A., Schroeder, B., et al. (2013). Prediction of late distant recurrence in estrogen receptor positive breast cancer patients: prospective comparison of the breast cancer index (BCI), Oncotype DX recurrence score and IHC4 in TransATAC. Lancet Oncology, 14 (11), 1067-1076.  (Level 4 evidence)

Xin, L., Liu, Y.H., Martin, T.A., & Jiang, W.G. (2017). The era of multigene panels comes? The clinical utility of OncotypeDX and MammaPrint. World Journal of Oncology, 8 (2), 34-40. (Level 2 evidence)

Zhang, Y., Schnabel, C., Schroeder, B., Jerevall, P., Jankowitz, R., Fornander, T., et al. (2013). Breast cancer index identifies early-stage estrogen receptor-positive breast cancer patients at risk for early and late - distant recurrence. Clinical Cancer Research, 19 (15), 4196-4205. Abstract retrieved January 9, 2017 from PubMed database.




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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