CurrentBlue Cross Blue Shield - Rhode IslandPolicy N/A

Medical Coverage Policy Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer

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).

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Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMedical Coverage Policy Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 1, 2024

Next Review Date

Key ActionObtain prior authorization for listed tests for Medicare Advantage and use the online tool (recommended for Commercial) before ordering assays such as Breast Cancer Index, EndoPredict, Oncotype DX Breast, MammaPrint, MammaPrint NGS, Oncotype DX Breast DCIS Score, and Prosigna.

SourceLink

POLICY UPDATE CHANGES

No material clinical/coverage changes in this update.

7Medically necessary tests (MA)

2Not covered / insufficient evidence (MA)

7Medically necessary tests (Commercial)

2Not medically necessary / insufficient (Commercial)

includedReferences cited

Coverage Summary

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.

Key thresholds and dates

DCIS specimen minimum lengthFFPE specimen with at least 0.5 mm of DCIS length

MammaPrint ordering timeframeWhen ordered within 6 months after diagnosis

Effective date2024-01-01

Policy last review2023-09-20

Medical-Necessity Criteria

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

Patient has early-stage disease (T1-3, pN0-N1, M0).
Pathology reveals invasive carcinoma of the breast that is ER-positive and/or PR-positive and HER2-negative.
Patient has no evidence of distant breast cancer metastasis (i.e., non-relapsed).
Test results will be used in determining treatment management of the patient for chemotherapy and/or extension of endocrine therapy.

Oncotype DX Breast CPT 81519

Not Covered / Insufficient Evidence

BluePrint and DCISionRT - Not covered / insufficient evidence

Tests not covered due to insufficient evidence to determine effects on health outcomes:

ANY of the following

BluePrint is not covered (insufficient evidence for required clinical utility)
DCISionRT is not covered (evidence insufficient; retrospective validation studies only)

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.

Coding

Covered CPT codes (may be considered medically necessary when criteria met)CPTCovered

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

Not covered / not medically necessary CPT codesCPTNot Covered

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

Requires authorization (Unlisted / Other tests)CPT|mixedCovered

81479

Unlisted molecular pathology procedure - requires authorization for Medicare Advantage Plans and Commercial Products for tests without a specific CPT code

Provider Actions & Requirements

Prior Authorization

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.

81518
81522
81519
81521
81523
0045U
81520

Prior Authorization

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.

Background & Evidence

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.

Medicare Determinations

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

Revision History

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyMedical Coverage Policy Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer

Policy CodePolicy N/A

Change TypeNo material change

Effective DateJan 1, 2024

Next Review Date

SourceLink

On This Page

Oncotype DX Breast may be considered medically necessary for members with the following findings:

ANY of the following

Estrogen-receptor positive, node-negative carcinoma of the breast (stage I–II) for consideration of adjuvant chemotherapy.
Estrogen-receptor positive breast carcinoma with 1–3 positive nodes when test result will influence chemotherapy decision making.
Estrogen-receptor positive micrometastases of carcinoma of the breast when test result will influence systemic therapy decisions.

Prosigna CPT 81520

Prosigna may be considered medically necessary for members meeting either of the following:

ANY of the following

ER-positive, lymph node-negative, stage I or II breast cancer when results will inform prognosis and adjuvant therapy decisions.
ER-positive, lymph node-positive (1–3 positive nodes), stage II breast cancer when test results will influence chemotherapy decisions.

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

Unilateral tumor.
Hormone receptor–positive (estrogen receptor–positive or progesterone receptor–positive).
Stage T1 or T2 primary tumor.
HER2-negative.
One to three positive lymph nodes (N1) or node-negative when clinical context indicates chemotherapy is a therapeutic option.
Will be treated with adjuvant endocrine therapy (e.g., tamoxifen, aromatase inhibitors).
Test result will aid in deciding on chemotherapy (i.e., when chemotherapy is a therapeutic option).
Patient eligible for a chemotherapy regimen containing a taxane, an anthracycline, or both.
Test is ordered within 6 months after diagnosis.

High clinical risk (for MammaPrint)

Grade: well differentiated; tumor size 2.1 to 5 cm.
Grade: moderately differentiated; any tumor size.
Grade: poorly differentiated or undifferentiated; any tumor size.

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

Patient is post-menopausal.
Patient is either lymph node–negative or has 1–3 positive lymph nodes.
Pathology (excisional or biopsy) reveals invasive carcinoma of the breast that is ER-positive and HER2-negative.
Patient has no evidence of distant metastasis.
Test result will be used to determine treatment choice between endocrine therapy alone versus endocrine therapy plus chemotherapy.

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

Pathology (excisional or core biopsy) reveals ductal carcinoma in situ (DCIS) of the breast with no pathological evidence of invasive disease.
Patient is a candidate for and is considering breast-conserving surgery alone as well as breast-conserving surgery combined with adjuvant radiation therapy.
FFPE specimen with at least 0.5 mm of DCIS length.
Test result will be used to determine treatment choice between surgery alone versus surgery with radiation therapy.
Patient has not received and is not planning on receiving mastectomy.

Documentation Required

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.

Denial Risk

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.

Billing Rule

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.

81479

Billing Rule

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.

Denial Risk

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.

81518
81519
81520
81521
81522
81523

Documentation Required

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.

Denial Risk

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.