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
Breast cancer gene expression assay is considered medically necessary if the medical appropriateness criteria are met. (See Medical Appropriateness below.)
Breast cancer gene expression assay is considered investigational for other indications including, but not limited to, the following:
Noninvasive ductal carcinoma in situ (i.e., Oncotype DX® Breast DCIS Score)
When performed using BluePrint® 80-gene molecular subtyping assay
When performed using InsightTNBCType®
MEDICAL APPROPRIATENESS
Breast cancer gene expression assay is considered medically appropriate if ANY ONE of the following are met:
Test results will guide decision-making regarding adjuvant chemotherapy and ALL of the following:
Newly diagnosed carcinoma of breast
Primary, invasive breast cancer
Human epidermal growth factor receptor 2 (HER2) negative
Indicated when ANY ONE of the following tests is used:
MammaPrint® when ALL of the following are met:
Female breast cancer
Tumor size > 0.5 cm (5mm) in greatest dimension (T1b-T3)
Estrogen receptor positive (ER+)
Lymph node status is ANY ONE of the following:
No regional lymph node metastasis (pN0)
Involvement of 1-3 positive ipsilateral axillary lymph nodes
Oncotype DX® when ALL of the following are met:
Male or Female breast cancer
Tumor size > 0.5 cm (5mm) in greatest dimension (T1b-T3)
Estrogen receptor positive (ER+)
Lymph node status is ANY ONE of the following:
No regional lymph node metastasis (pN0)
Involvement of 1-3 positive ipsilateral axillary lymph nodes
EndoPredict® when ALL of the following are met:
Female breast cancer
Unilateral tumor
Tumor size > 0.5 cm (5mm) in greatest dimension (T1b-T3)
Hormone receptor positive (ER+ or PR+)
Lymph node status is ANY ONE of the following:
No regional lymph node metastasis (pN0)
Involvement of 1-3 positive ipsilateral axillary lymph nodes
Breast Cancer Index™ when ALL of the following are met:
Female breast cancer
Unilateral tumor
Tumor size > 0.5cm (5mm) in greatest dimension (T1b-T3)
Hormone receptor positive (ER+ or PR+)
Lymph node status is ANY ONE of the following:
Individual has no regional lymph node metastasis (pN0)
Micrometastases (pN1mi, malignant cells in regional lymph node(s) not greater than 2.0mm)
Prosigna® when ALL of the following are met:
Female breast cancer
Tumor size equal to or greater than 0.4 cm (4mm) in greatest dimension (T1b-T3)
Hormone receptor positive (ER+/PR+)
No regional lymph node metastasis
Test results will predict benefit of extended endocrine therapy beyond five years when ALL of the following are met:
Test performed using Breast Cancer Index™
Female breast cancer
Unilateral tumor
Tumor size > 0.5cm (5mm) in greatest dimension (T1b-T3)
Hormone receptor positive (ER+ or PR+)
Lymph node status is 0 – 3 positive nodes
IMPORTANT REMINDERS
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
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 or government program (e.g., TennCare), the express terms of the health plan or government program will govern.
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. (12:2023). Assays of genetic expression in tumor tissue as a technique to determine prognosis in patients with breast cancer (2.04.36). Retrieved February 5, 2024 from http://www.evidencepositioningsystem.com. (84 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)
CMS.gov: Centers for Medicare and Medicaid Services. Palmetto GBA. (2021, April). MolDX: Breast cancer assay: Prosigna (LCD ID: L36125). Retrieved November 9, 2021 from https://www.cms.gov.
CMS.gov: Centers for Medicare and Medicaid Services. Palmetto GBA. (2021, October). MolDX: Breast cancer Index Gene Expression Test (LCD ID: L37794). Retrieved November 9, 2021 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. (2024, January). Clinical guidelines: Lab management program. Retrieved February 5, 2024 from www.evicore.com.
Harnan, S., Tappenden, P., Cooper, K., Stevens, J., Bessey, A., Rafia, R., 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 Journals Library; Health Technology Assessment (Southampton, UK), 23 (30), 1–328, doi: 10.3310/hta23300. (Level 1 evidence)
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)
Lemij, A. A., Baltussen, J. C., de Glas, N. A., Kroep, J. R., Derks, M. G. M., Liefers, G. J., & Portielje, J. E. A. (2023). Gene expression signatures in older patients with breast cancer: A systematic review. Critical Reviews in Oncology/Hematology, 181, 103884, doi: 10.1016/j.critrevonc.2022.103884. (Level 2 evidence)
National Comprehensive Cancer Network. (2024, January). NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®). Breast cancer. Version 1.2024. Retrieved February 5, 2024 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)
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: 3/14/2024
ID_EC
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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