ModifiedBlue Cross Blue Shield - Rhode IslandPolicy N/A

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

Defines medical necessity, prior authorization, and coverage stance for multigene and protein-expression assays performed on breast tumor tissue to determine prognosis and guide adjuvant therapy decisions for BCBSRI members.

Policy Summary

PayerBlue Cross Blue Shield - Rhode Island

PolicyAssays of Genetic Expression in Tumor Tissue to Determine Prognosis in Breast Cancer

Policy CodePolicy N/A

Change TypeMaterial coverage and operational clarifications (added, revised, clarified)

Effective Date07|01|2025

Next Review DateN/A

Key ActionObtain prior authorization via the online authorization tool before ordering Oncotype DX Breast DCIS Score (CPT 0045U); laboratories must not obtain authorizations on behalf of ordering physicians.

SourceLink

POLICY UPDATE CHANGES

Oncotype DX Breast DCIS Score (CPT 0045U) is considered medically necessary effective 07/01/2025 when online authorization criteria are met.

BluePrint (0630U/81479) and DCISionRT (0295U) are stated as not covered for Medicare Advantage Plans and not medically necessary for Commercial Products.

Prior authorization rules clarified: laboratories may not obtain authorization or participate on behalf of ordering physicians; unlisted CPT codes require prior authorization.

3named tests addressed

0045Umedically necessary CPT

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Coverage Criteria

inv-01: Oncotype DX Breast DCIS Score — medically necessary when online authorization criteria met

Covered when ALL of the following are met:

Oncotype DX Breast DCIS Score medical necessity: Effective 7/1/2025, Oncotype DX Breast DCIS Score (CPT 0045U) is considered medically necessary when the medical criteria in the online authorization tool for participating providers is met.

Ordering providers must use the online authorization tool to confirm that the member meets the medical criteria before testing is performed.

inv-02: Not medically necessary / Not covered — BluePrint and DCISionRT

Not covered / Not medically necessary:

BluePrint and DCISionRT coverage stance: BluePrint (CPT 0630U) and DCISionRT (CPT 0295U) are not covered for Medicare Advantage Plans and are not medically necessary for Commercial Products because the evidence is insufficient to determine effects on health outcomes.

Specific CPT codes 0630U and 0295U are referenced as not covered/not medically necessary.

Some genetic testing services may be a contract exclusion for self‑funded groups that have excluded expanded biomarker testing per the state mandate (R.I.G.L. §27‑19‑81). Coverage for tests subject to such exclusions depends on the member's specific benefit booklet and employer agreement; providers should verify whether the member's plan includes the expanded biomarker testing benefit before ordering.

This medical policy is provided for informational purposes and is not a guarantee of payment. Benefits and eligibility are determined by the member's subscriber agreement, member certificate, and/or employer agreement, which supersede the policy. Providers should confirm member benefits and obtain any required authorizations prior to performing services.

Per this policy, BluePrint (BluePrint® Molecular Subtyping Test; CPT 0630U) and DCISionRT (CPT 0295U) are considered not medically necessary for Commercial Products and not covered for Medicare Advantage Plans due to insufficient evidence of impact on health outcomes.

Services determined to be not medically necessary or non‑covered benefits may not be charged to the member unless the member has been informed in advance and has provided written agreement to pay out of pocket. Providers should contact the provider call center to verify member‑specific benefits; subscriber agreements and employer agreements supersede this medical policy.

Covered Indications

inv-25: Use of Oncotype DX Breast DCIS Score for ductal carcinoma in situ when online authorization criteria are met.

Use of Oncotype DX Breast DCIS Score for ductal carcinoma in situ is supported when online authorization criteria are satisfied:

Indication: Test: Oncotype DX Breast DCIS Score (CPT 0045U) for ductal carcinoma in situ (DCIS).

CPT 0045U description: mRNA gene expression profiling by RT‑PCR of 12 genes on FFPE tissue, algorithm reported as recurrence score.

Authorization: Medical criteria in the payer's online authorization tool are met prior to testing.

Participating providers must use the online authorization tool to confirm medical criteria; prior authorization is required per policy.

inv-26: Use of multigene assays to predict recurrence risk and guide adjuvant systemic therapy decisions in early-stage breast cancer — supported by references

Use of multigene assays to predict recurrence risk and guide adjuvant systemic therapy decisions in early-stage breast cancer — evidence summary and guidance:

Coding

Covered CPT Codes (when criteria met)CPTCovered

0045U

Oncology (breast ductal carcinoma in situ), mRNA, gene expression profiling by real-time RT-PCR of 12 genes (7 content and 5 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as recurrence score

Not covered / Not medically necessary or requires prior authCPTNot Covered

0295U	Oncology (breast ductal carcinoma in situ), protein expression profiling by immunohistochemistry of 7 proteins (COX2, FOXA1, HER2, Ki-67, p16, PR, SIAH2), with 4 clinicopathologic factors (size, age, margin status, palpability), utilizing formalin-fixed paraffin-embedded (FFPE) tissue, algorithm reported as a recurrence risk score
0630U	Oncology (breast), mRNA, gene expression profiling by micro-array of 80 genes (80 content and 465 housekeeping), utilizing formalin-fixed paraffin-embedded tissue (FFPE), algorithm reported as index that is diagnostic of a molecular subtype (luminal, basal, Her2)
81479	Unlisted molecular pathology procedure

Referenced CPT codes in Genetic Testing Services policyCPT

81518	Breast Cancer Index (Biotheranostics)
81519	Oncotype DX Breast (Genomic Health)
81520	Prosigna (NanoString Technologies)
81521	MammaPrint (Agendia)
81522	EndoPredict (Myriad)
81523	MammaPrint NGS (Agendia)

DCISionRT — low‑risk threshold

DCISionRT low-risk thresholdRT score < 3

Score components7 protein markers (COX-2, FOXA1, HER2, Ki-67, p16/INK4A, PR, SIAH2) plus 4 clinicopathologic factors (age, tumor size, palpability, surgical margin status)

Risk groups producedStratifies DCIS into low risk, elevated risk with good response, and elevated risk with poor response

Intended usePredict radiation benefit after breast-conserving surgery for DCIS

Provider Actions and Requirements

Prior Authorization

Prior Authorization Required

Prior authorization is required for Medicare Advantage Plans and recommended for Commercial Products via the online tool for participating providers for the following tests: Oncotype DX Breast DCIS Score. There is no specific CPT coding for some of the services referenced in this policy; use an Unlisted CPT code (see Coding Section). All unlisted genetic testing CPT codes require prior authorization to determine the specific service rendered and whether it is covered or medically necessary.

81479 — Unlisted molecular pathology procedure

Denial Risk

Laboratory-Provided Unauthorized Services

Laboratories are not permitted to obtain clinical authorization or otherwise participate in the authorization process on behalf of the ordering physician. Only the ordering physician shall be involved in the authorization, appeal, or other administrative processes related to prior authorization or medical necessity.

If a laboratory provides a laboratory service that has not been authorized, the service will be denied and the financial liability will rest with the participating laboratory; the laboratory may not bill the member.

Definitions

BluePrint — 80‑gene mRNA microarray profile

DefinitionBluePrint is an 80-gene mRNA microarray molecular subtyping profile that classifies breast tumors into Basal, Luminal, and ERBB2 (HER2) molecular subtypes

MethodmRNA microarray profiling using an 80-gene signature

PurposeIntended to inform prognosis and treatment decisions by identifying intrinsic molecular subtypes

Coverage stance in policyListed as not covered / not medically necessary (CPT 0630U or 81479) due to insufficient evidence

DCISionRT — combined protein‑expression and clinicopathologic algorithm

DefinitionDCISionRT is a combined algorithm incorporating protein-expression of 7 monoclonal markers and 4 clinicopathologic factors to produce a recurrence risk (RT) score

Not Covered

Not covered: BluePrint (CPT 0630U) and DCISionRT (CPT 0295U) are explicitly listed as not covered for Medicare Advantage Plans and not medically necessary for Commercial Products under this policy.

Background

Background: mRNA‑based and protein‑expression multigene assays analyze tumor tissue to provide prognostic or predictive scores intended to estimate recurrence risk and help guide adjuvant therapy decisions (for example, the need for chemotherapy, radiation after breast‑conserving surgery for DCIS, or extended endocrine therapy). These assays include mRNA expression profiling and protein immunohistochemistry panels and are used to stratify patients by risk and potential treatment benefit, though the strength of evidence and demonstrated clinical utility vary by test.

References

References: Key studies and guideline updates cited in support of multigene expression assays include foundational work on the 21‑gene Recurrence Score (Paik et al., N Engl J Med 2004; Paik et al., J Clin Oncol 2006), prospective validation and outcome studies (Sparano et al., N Engl J Med 2015 and 2018), comparative and performance analyses of multiple prognostic signatures (Sestak et al.; Filipits et al.; Dowsett et al.), trials assessing use of gene signatures to inform chemotherapy decisions (e.g., Plan B, WSG; Nitz et al.), and guideline statements from ASCO and other expert groups summarizing the role of biomarkers in guiding adjuvant systemic therapy (Burstein et al.; ASCO focused updates). Additional referenced literature addresses prognostic signatures for DCIS, PAM50/Prosigna, MammaPrint (70‑gene), Breast Cancer Index, HOXB13/IL17BR, and clinical utility studies such as Solin et al. and Shah et al. (DCISionRT clinical utility).

Revision History

2025-07-01material_changeLatest

Oncotype DX Breast DCIS Score (CPT 0045U) is considered medically necessary when the medical criteria in the online authorization tool for participating providers is met.

2025-07-01material_change

BluePrint (CPT 0630U) and DCISionRT (CPT 0295U) are listed as not covered for Medicare Advantage Plans and not medically necessary for Commercial Products due to insufficient evidence.

2025-07-01operational_clarification

Prior authorization requirements clarified: prior authorization is required (Medicare Advantage) or recommended (Commercial) via the online tool for participating providers; unlisted genetic testing CPT codes require prior authorization and laboratories are not permitted to obtain or facilitate authorizations on behalf of ordering physicians.