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Policy governs coverage and prior authorization for multi-gene expression assays (eg, Breast Cancer Index, Oncotype DX, MammaPrint, Prosigna, EndoPredict, Oncotype DX DCIS, MammaPrint NGS, BluePrint, DCISionRT) used to determine prognosis and guide adjuvant therapy decisions in breast cancer for Medicare Advantage Plans and Commercial Products. It defines clinical criteria for medical necessity, tests considered not covered, coding, and prior authorization requirements (part 1 of 2).
No material clinical/coverage changes in this update.
This policy covers specific multigene mRNA expression assays used to estimate prognosis and guide adjuvant therapy decisions in breast cancer, including Breast Cancer Index (CPT 81518), Oncotype DX Breast (CPT 81519), MammaPrint (CPT 81521), Prosigna (CPT 81520), EndoPredict (CPT 81522), Oncotype DX Breast DCIS Score (CPT 0045U), and MammaPrint NGS (CPT 81523); the policy also references BluePrint and DCISionRT (tests with different coverage status).
Applicable test populations addressed include patients with ER and/or PR positive, HER2‑negative invasive breast cancer (node‑negative and patients with 1–3 positive nodes in specified indications) and patients with ductal carcinoma in situ (DCIS) for the DCIS assay. Coverage determinations and medical‑necessity criteria differ between Medicare Advantage Plans and Commercial Products, and providers are instructed to verify member benefits and applicable contract exclusions.
Breast Cancer Index CPT 81518
Breast Cancer Index may be considered medically necessary for members with invasive breast cancer when the following criteria are met:
ALL of the following
Oncotype DX Breast CPT 81519
Oncotype DX Breast may be considered medically necessary for members with the following findings:
ANY of the following
Prosigna CPT 81520
Prosigna may be considered medically necessary for members meeting either of the following:
ANY of the following
MammaPrint CPT 81521; MammaPrint NGS CPT 81523
The use of the MammaPrint assay to determine recurrence risk for deciding whether to undergo adjuvant chemotherapy may be considered medically necessary in members with primary, invasive breast cancer meeting all of the following characteristics:
ALL of the following
EndoPredict CPT 81522
EndoPredict may be considered medically necessary for members with T1-3, N0-1 breast cancer when the following criteria are met:
ALL of the following
Oncotype DX Breast DCIS Score CPT 0045U
The Oncotype DX DCIS assay may be considered medically necessary when the following clinical conditions are met:
ALL of the following
BluePrint and DCISionRT - Not covered / insufficient evidence
Tests not covered due to insufficient evidence to determine effects on health outcomes:
ANY of the following
The policy explicitly lists BluePrint and DCISionRT (CPT 0295U) as tests not covered or not medically necessary because the evidence is insufficient to determine effects on health outcomes (DCISionRT noted to have only retrospective validation studies). Coverage for these tests differs by product type: both Medicare Advantage and Commercial Products designate these tests as not covered / not medically necessary, and other coverage distinctions in the policy depend on the member’s product and contract.
| 81518 | Breast Cancer Index: mRNA, RT-PCR of 11 genes, FFPE tissue, risk % for metastatic recurrence and benefit from extended endocrine therapy |
| 81519 | Oncotype DX Breast: mRNA, RT-PCR of 21 genes, FFPE tissue, algorithm reported as recurrence score |
| 81520 | Prosigna: mRNA gene expression profiling by hybrid capture of 58 genes, FFPE tissue, recurrence risk score |
| 81521 | MammaPrint: mRNA microarray profiling of 70 content genes, FFPE or fresh frozen tissue, index related to risk of distant metastasis |
| 81522 | EndoPredict: mRNA, RT-PCR of 12 genes, FFPE tissue |
| 81523 | MammaPrint NGS: mRNA NGS profiling of 70 content genes and 31 housekeeping genes, FFPE tissue |
| 0045U | Oncotype DX Breast DCIS Score: mRNA, RT-PCR of 12 genes and 5 housekeeping, FFPE tissue, recurrence score |
| 0295U | DCISionRT: expression profiling by immunohistochemistry of proteins with 4 clinicopathologic factors, FFPE tissue, recurrence risk score - not covered for Medicare Advantage and not medically necessary for Commercial |
| 81479 | Unlisted molecular pathology procedure - requires authorization for Medicare Advantage Plans and Commercial Products for tests without a specific CPT code |
Prior authorization required for Medicare Advantage; recommended for Commercial
Prior authorization is required for Medicare Advantage plans and is recommended for Commercial Products for the listed multigene assays. Providers should obtain authorization via the online tool for participating providers before ordering these tests.
Authorization required for unlisted genetic testing CPT codes
Unlisted genetic testing CPT codes (for example, 81479) require authorization to determine the specific service rendered and whether it is covered. Authorization must be obtained by the ordering physician; laboratories may not obtain authorization on the physician's behalf.
Ordering physician must handle authorization/appeals
Only the ordering physician may be involved in authorization, appeal, or other administrative processes. Use of laboratory representatives or third parties to obtain authorization or appeals is a violation and may result in severe action, up to termination from the provider network.
Laboratory-performed unauthorized services denied to laboratory
If a laboratory provides a laboratory service that has not been authorized, the service will be denied and the financial liability falls to the participating laboratory; such services may not be billed to the member.
Use of unlisted CPT for services without specific code
When no specific CPT code exists for a referenced service, use an Unlisted CPT code (e.g., 81479). Unlisted molecular pathology procedures require prior authorization to determine coverage.
Coverage differs by product
Coverage (medically necessary vs not covered) differs between Medicare Advantage Plans and Commercial Products. Providers must verify member benefits and any applicable contract exclusions in the Benefit Booklet or Evidence of Coverage before ordering.
Multiple tests not medically necessary (Commercial only)
For Commercial Products only, ordering more than one of these tests to determine the necessity of adjuvant therapy is considered not medically necessary and may be denied: multiple tests should not be used concurrently to determine necessity.
Policy informational use and payer determination
This medical policy is provided for informational purposes only and is not a guarantee of payment. Benefits and eligibility are determined by the member's subscriber agreement or employer agreement, which supersede this policy.
Potential member liability for non-covered services
If services are determined to be not medically necessary or are non-covered benefits, providers may not charge the member unless the member has been informed and has agreed in writing in advance to pay for the service; otherwise the member may be held liable for non-covered services only with prior written agreement.
Multigene mRNA expression assays measure expression of gene panels in tumor tissue (typically FFPE) to estimate risk of distant recurrence and to predict potential benefit from adjuvant chemotherapy or from extended endocrine therapy. These assays (for example, the 11‑gene Breast Cancer Index, the 21‑gene Oncotype DX, the 70‑gene MammaPrint, Prosigna's PAM50 signature, EndoPredict, and DCIS assays) provide prognostic and in some cases predictive information intended to be used alongside clinicopathologic factors to guide decisions about chemotherapy, radiation, and duration of endocrine therapy.
The policy defines clinical criteria for when each test may be considered medically necessary (for example, ER+/PR+, HER2‑ tumors in specified stage/node settings, and DCIS specimen requirements) and requires prior authorization for listed tests for Medicare Advantage and recommends prior authorization for Commercial Products. Coverage (medically necessary versus not covered/not medically necessary) and rules such as restrictions on use of multiple tests vary between Medicare Advantage Plans and Commercial Products, so providers must confirm member‑specific benefits.
| Reference type | Details |
|---|---|
| Policy references | Multiple CMS MolDX LCDs and articles (eg L37822, L36386, L37295, L36941) and guideline sources (NCCN, ASCO) and multiple peer-reviewed studies cited |
| Selected citations | Multiple references to ASCO guidelines, St. Gallen consensus, and journal publications (e.g., J Clin Oncol 2019; Ann Oncol 2017/2019) are listed in the excerpt. |
Glossary: FFPE = Formalin‑Fixed, Paraffin‑Embedded tissue; ER = Estrogen Receptor; PR = Progesterone Receptor; HER2 = Human Epidermal Growth Factor Receptor 2; DCIS = Ductal Carcinoma In Situ.
| Name | Number | Type |
|---|---|---|
| MolDX: Breast Cancer Index (BCI) Gene Expression Test | L37822 | LCD |
| MolDX: Breast Cancer Prosigna Assay | L36386 | LCD |
| MolDX: EndoPredict Breast Cancer Gene Expression Test | L37295 | LCD |
| MolDX: Oncotype DX Breast Cancer for DCIS | L36941 | LCD |
High clinical risk (for MammaPrint)