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

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

Indications

(1) Does the request meet this criterion: BluePrint (Agendia) (CPT code 81479)? 
(2) Does the request meet this criterion: DCISionRT® (Prelude Corporation) (CPT code 0295U) MEDICAL CRITERIA Medicare Advantage Plans and Commercial Products Oncotype DX Breast DCIS Score – CPT 0045U Effective 7/1/2025, this test is considered medically necessary when the medical criteria in the online? 
(3) Does the request meet this criterion: Oncotype DX Breast DCIS Score There is no specific CPT coding for some of the services referenced in this policy. Therefore, an Unlisted CPT code should be used (see Coding Section for details). All Unlisted genetic testing CPT codes require? 
(4) Does the request meet this criterion: Oncotype DX Breast DCIS Score The following test(s) are not covered for Medicare Advantage Plans and not medically necessary for Commercial Products as the evidence is insufficient to determine the effects of the technology on health? 
(5) Does the request meet this criterion: DCISionRT Some genetic testing services are not covered and a contract exclusion for any self-funded group that has excluded the expanded coverage of biomarker testing related to the state mandate, R.I.G.L. §27-19-81 described? 

Effective Date

NA

Last Reviewed

NA

Original Document

  Reference



500 EXCHANGE STREET, P ROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 1 (401) 274-4848 WWW.BCBSRI.COM EFFECTIVE DATE: 07|01|2025 POLICY LAST REVIEWED: 05|07|2025

OVERVIEW Laboratory tests have been developed to detect the expression, via messenger RNA, of different genes in breast tumor tissue and combine the results to determine prognosis in individuals with breast cancer. Test results may help providers and individuals decide whether to include adjuvant chemotherapy in the postsurgical management of breast cancer, to alter treatment in individuals with ductal carcinoma in situ (DCIS) or triple- negative (estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2) breast cancer (TNBC), or to recommend extended endocrine therapy in individuals who are recurrence-free at five years.
The following tests are addressed in this policy: • BluePrint (Agendia) (CPT code 81479) • DCISionRT® (Prelude Corporation) (CPT code 0295U) MEDICAL CRITERIA Medicare Advantage Plans and Commercial Products Oncotype DX Breast DCIS Score – CPT 0045U Effective 7/1/2025, this test is considered medically necessary when the medical criteria in the online authorization tool for participating providers is met.
PRIOR AUTHORIZATION 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. Therefore, an Unlisted CPT code should be used (see Coding Section for details). All Unlisted genetic testing CPT codes require prior authorization to determine what service is being rendered and if the service is covered or not medically necessary. See the Related Policies section. Note: Laboratories are not allowed to obtain clinical authorization or 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/medical necessity.
In no circumstance shall a laboratory or a physician/provider use a representative of a laboratory or anyone with a relationship to a laboratory and/or a third party to obtain authorization on behalf of the ordering physician, to facilitate any portion of the authorization process or any subsequent appeal of a claim where the authorization process was not followed and/or a denial for clinical appropriateness was issued, including any element of the preparation of necessary documentation of clinical appropriateness. If a laboratory or a third party is found to be supporting any portion of the authorization process, BCBSRI will deem the action a violation of this policy and severe action will be taken up to and including termination from the BCBSRI provider network. If a laboratory provides a laboratory service that has not been authorized, the service will be denied as the financial liability of the participating laboratory and may not be billed to the member. POLICY STATEMENT Medicare Advantage Plans and Commercial Products Medical Coverage Policy | Assays of Genetic Expression in Tumor Tissue as a Technique to Determine Prognosis in Patients with Breast Cancer

500 EXCHANGE STREET, P ROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 2 (401) 274-4848 WWW.BCBSRI.COM

Effective 7/1/2025, the following test(s) may be considered medically necessary when the medical criteria in the online authorization tool for participating providers is met:
• Oncotype DX Breast DCIS Score

The following test(s) are not covered for Medicare Advantage Plans and not medically necessary for Commercial Products as the evidence is insufficient to determine the effects of the technology on health outcomes:
• BluePrint
• DCISionRT

Some genetic testing services are not covered and a contract exclusion for any self-funded group that has excluded the expanded coverage of biomarker testing related to the state mandate, R.I.G.L. §27-19-81 described in the Biomarker Testing Mandate policy. For these groups, a list of which genetic testing services are covered with prior authorization, are not medically necessary or are not covered because they are a contract exclusion can be found in the Coding section of the Genetic Testing Services or Proprietary Laboratory Analyses policies. Please refer to the appropriate Benefit Booklet to determine whether the member’s plan has customized benefit coverage. Please refer to the list of Related Policies for more information.

COVERAGE Benefits may vary between groups and contracts. Please refer to the appropriate Benefit Booklet, Evidence of Coverage, or Subscriber Agreement for laboratory tests and applicable not covered/not medically necessary benefits/coverage.

BACKGROUND BluePrint Molecular subtyping profile or BluePrint is proposed for the evaluation of an individual’s prognosis when diagnosed with breast cancer. The multigene profile classifies breast cancer into basal type, luminal type and ERBB type (HER2/neu positive) molecular subclasses to stratify an individual’s risk to purportedly assist with treatment decisions. Aetna Agendia BluePrint has an 80-gene profile that classifies breast cancer into molecular subtypes. The profile separates tumors into Basal-type, Luminal-type and ERBB2-type subgroups by measuring the functionality of downstream genes for each of these molecular pathways to inform the physician of the potential effect of adjuvant therapy.

There is insufficient evidence to support the required clinical utility for BluePrint. The evidence is insufficient to determine the effects of the technology on health outcomes.

DCISionRT The DCISionRT combines 7 monoclonal protein markers (COX-2, FOXA1, HER2, Ki-67, p16/INK4A, PR, and SIAH2) assessed in tumor tissue with 4 clinicopathologic factors (age at diagnosis, tumor size, palpability, and surgical margin status) to produce a score that stratifies individuals with DCIS into 3 risk groups: low risk, elevated risk with good response, and elevated risk with poor response. The purpose of the test is to predict radiation benefit in individuals with DCIS following breast conserving surgery.

For individuals who have DCIS considering radiotherapy who receive gene expression profiling with DCISionRT, the evidence includes retrospective validation studies. One Simon et al (2009) category B study provided evidence for clinical validity which showed no benefit of radiation therapy among a group of participants classified as low risk using the DCIS RT score at a threshold of <3 (absolute risk difference for invasive recurrence 1.2% (-5.7% to 8.2%). However, it is unclear whether the estimated 10-year recurrence risk for this group (12.4%; 95% CI 7.2% to 20.8% for invasive recurrence) is low enough to consider hanging management or is estimated with sufficient precision. Conclusions are also limited because there are no comparison recurrence estimates for women based on the standard of care (risk predictions based on clinical algorithms). The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

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CODING The following CPT code(s) may be considered medically necessary for Medicare Advantage Plans and Commercial Products when the medical criteria in the online authorization tool for participating providers is met:

This code can be used for Oncotype DX Breast DCIS (Ductal Carcinoma In Situ) Score: 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

Please refer to the Genetic Testing Services policy for the following CPT codes and associated ICD-10-CM codes that are considered medically necessary. • Breast Cancer Index (Biotheranostics) (CPT code 81518) • Oncotype DX Breast (Genomic Health) (CPT code 81519) • Prosigna (NanoString Technologies) (CPT code 81520) • MammaPrint (Agendia) (CPT code 81521) • EndoPredict (Myriad) (CPT code 81522) • MammaPrint NGS (Agendia) (CPT code 81523)

The following CPT code(s) are not covered for Medicare Advantage Plans and not medically necessary for Commercial Products. This code can be used for DCISionRT: 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

The following CPT code requires prior authorization for Medicare Advantage Plans and Commercial Products. The code can be used for any test identified in this policy that does not have a specific CPT code (e.g. BluePrint). 81479 Unlisted molecular pathology procedure

RELATED POLICIES Biomarker Testing Mandate
Genetic Testing Services Proprietary Laboratory Analyses (PLA) and Multianalyte Assays with Algorithmic Analyses (MAAA) Unlisted Procedures

PUBLISHED Provider Update, July 2025 Provider Update, September 2024 Provider Update, February/November 2023 Provider Update, February 2022 Provider Update, June/September 2021

REFERENCES

  1. Centers for Medicare and Medicaid Services (CMS). Local Coverage Determination (LCD): MolDX: Molecular Diagnostic Tests (MDT) (L35160)
  2. Centers for Medicare and Medicaid Services (CMS). Local Coverage Determination (LCD): MolDX: Proteomics Testing (A59641)
  3. Centers for Medicare and Medicaid Services (CMS). Local Coverage Article: Billing and Coding: MolDX: BLUEPRINT® Test (A55115)

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and arimidex, tamoxifen alone or in combination randomized trials using the PAM50 risk of recurrence score. J Clin Oncol. Mar 10 2015; 33(8): 916-22. PMID 25332252

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500 EXCHANGE STREET, P ROVIDENCE, RI 02903-2699 MEDICAL COVERAGE POLICY | 8 (401) 274-4848 WWW.BCBSRI.COM

  1. Curigliano G, Burstein HJ, Winer EP, et al. De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017. Ann Oncol. Aug 01 2017; 28(8): 1700-1712. PMID 28838210
  2. Burstein HJ, Curigliano G, Loibl S, et al. Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019. Ann Oncol. Oct 01 2019; 30(10): 1541-1557. PMID 31373601

  3. Shah C, Bremer T, Cox C, et al. The Clinical Utility of DCISionRT (R) on Radiation Therapy Decision Making in Patients with Ductal Carcinoma In Situ Following Breast-Conserving Surgery. Ann Surg Oncol. Oct 2021; 28(11): 5974-5984. PMID 33821346 i

    This medical policy is made available to you for informational purposes only. It is not a guarantee of payment or a substitute for your medical judgment in the treatment of your patients. Benefits and eligibility are determined by the member's subscriber a greement or member certificate and/or the employer agreement, and those documents will supersede the provisions of this medical policy. For information on member-specific benefits, call the provider call center. If you provide services to a member which are determined to not be medically necessary (or in some cases medically necessary services which are non-covered benefits), you may not charge the member for the services unless you have informed the member and they have agreed in writing in advance to continue with the treatment at their own expense. Please refer to your participation agreement(s) for the applicable provisions. This policy is current at the time of publication; however, medical practices, technology, and knowledge are constantly changing. BCBSRI reserves the right to review and revise this policy for any reason and at any time, with or without notice. Blue Cross & Blue Shield of Rhode Island is an independent licensee of the Blue Cross and Blue Shield Association. CLICK THE ENVELOPE ICON BELOW TO SUBMIT COMMENTS

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