BlueCross BlueShield of Tennessee Medical Policy Manual

Breast Cancer Gene Expression Assays

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018

DESCRIPTION

Laboratory tests have been developed to detect the expression of 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 individuals with early-stage breast cancer. Test results may help determine whether to include adjuvant chemotherapy in post-surgical management of breast cancer. In addition to guiding treatment decisions related to chemotherapy, Breast Cancer index™ has been validated to predict late distant recurrence risk and endocrine responsiveness when considering extension of endocrine therapy.

Most individuals with newly diagnosed, early-stage or nonmetastatic breast cancer are disease-free after initial local and regional treatment; however, almost a third of women develop metastasis by the 5 - 10 year follow-up.

Examples of Gene Expression Assays for Breast Cancer:

Test

Description

Breast Cancer Index™

6-11 gene predictor for risk of late recurrence at 5 to 10 years; Predictive of benefit of extended adjuvant endocrine therapy

EndoPredict®

12-gene molecular score for early and late recurrence

MammaPrint®

70 gene analysis; provides low - high risk classification for 10 year prognosis

Oncotype DX® for Breast Cancer

21-gene assay; Recurrence Score® of 0 - 100 provides 10-year prognosis information

Prosigna® (PAM 50)

Digital analysis system based on prediction of 50 gene microarray; giving a numerical value of 0-100 that correlates with the probability of recurrence within 10 years.

POLICY

MEDICAL APPROPRIATENESS

IMPORTANT REMINDERS

ADDITIONAL INFORMATION  

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. 

SOURCES 

American Society of Clinical Oncology. (2019). Role of patient and disease factors in adjuvant systemic therapy decision making for early-stage, operable breast cancer: update of the ASCO endorsement of the cancer care Ontario guidelines. Retrieved August 12, 2019 from https://ascopubs.org/doi/pdf/10.1200/JCO.19.00948.

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. Evidence Positioning System. (12:2020). Assays of genetic expression in tumor tissue as a technique to determine prognosis in patients with breast cancer (2.04.36). Retrieved February 2, 2021 from http://www.evidencepositioningsystem.com. (89 articles and/or guidelines reviewed)

Breast Cancer Index. (2020). Breast cancer intended use and limitations. Retrieved February 4, 2021 from https://www.breastcancerindex.com/.

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)

CMS.gov: Centers for Medicare and Medicaid Services. Palmetto GBA. (2019, November). MolDX: Breast cancer assay: Prosigna (LCD ID: L36125). Retrieved October 15, 2020 from https:///www..cms.gov. 

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)

eviCore healthcare. (2021, January). Clinical guidelines: Lab management program. Retrieved October 15, 2020 from www.evicore.com.

Harnan, S., Tappenden, K.C., Steven, J., Bessey, A., Rafia, R., Ward, S., et al. (2019). Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer: a systematic review and economic analysis. National Institute for Health Research, No. 23.30. Abstract retrieved August 9, 2019 from PubMed database.

Krop, I., Ismaila, N., Andre, F., Bast, R.C., Barlow, W., Collyar, D.E., et al. (2017). 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 focused update. Journal of Clinical Oncology, 35 (24), 2838-2847. (Level 1 evidence)

National Comprehensive Cancer Network. (2021, January). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Breast cancer. Version 1.2021. Retrieved February 2, 2021 from the National Comprehensive Cancer Network.

National Institute for Health and Care Excellence. (2018). Tumour profiling tests to guide adjuvant chemotherapy decisions in early breast cancer. Retrieved August 9, 2019 from www.nice.org.uk/guidance/dg10.

Noordhoek, I., Treuner, K., Putter, H., Zhang, Y., Wong, J., Meershoek-Klein Kranenbarg, E., et al. (2021). Breast cancer index predicts extended endocrine benefit to individualize selection of patients with HR+ early-stage breast cancer for 10 years of endocrine therapy. Clinical Cancer Research, 27 (1), 311-319. (Level 3 evidence)

Sestak, I., Buus, R., Cuzick, J., Dubsky, P., Kronenwett, R., Denkert, C., et al. (2018). Comparison of the performance of 6 prognostic signatures for estrogen receptor-positive breast cancer: a secondary analysis of a randomized clinical trial. JAMA Oncology, 4 (4), 545-553. Abstract retrieved November 26, 2018 from PubMed database.

Tan, W., Yang, M., Zhou, F., & Shen, W. (2018). Predicting the response to neoadjuvant therapy for early-stage breast cancer: tumor-, blood-, and imaging-related biomarkers. Cancer Research and Management, 10, 4333-4347. (Level 2 evidence)

Turashvili, G., Gonzalez-Loperena, M., Broqi, E., Dickler, M., Norton, L., Morrow, M., et al. (2018). The 21-gene recurrence score in male breast cancer. Annals of Surgical Oncology, 25 (6), 1530-1535. (Level 4 evidence)

U. S. Food and Drug Administration. (2007, June). Center for Devices and Radiologic Health, Premarket Notification Database. K141142 (MammaPrint®). Retrieved November 26, 2018 from http://www.fda.gov.

U. S. Food and Drug Administration. (2015, May). Center for Devices and Radiologic Health, Premarket Notification Database. K141771 (Prosigna™). Retrieved November 26, 2018 from http://www.fda.gov.

Van’t Veer, L.J., Yau, C., Yu, N.Y., Benz, C.C., Nordenskjold, B., Fornander, T., et al. (2017). Tamoxifen therapy benefit for patients with 70-gene signature high and low risk. Breast Cancer Research and Treatment, 166 (2), 593-601. (Level 1 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)

ORIGINAL EFFECTIVE DATE:  5/13/2017

MOST RECENT REVIEW DATE:  6/2/2021

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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