Blue Cross Blue Shield RI multigene assay Coverage

Coverage Criteria for Multigene Expression Assays

Breast Cancer Index - Medicare Advantage

Considered medically necessary when ALL of the following are met:

BCI criteria: Pathology reveals invasive carcinoma that is ER+ and/or PR+ and HER2-; patient has early-stage disease (T1-3, pN0, M0); no evidence of distant metastasis; patient is lymph node negative; test results will be used to determine chemotherapy and/or extension of endocrine therapy

Oncotype DX Breast - Medicare Advantage

Considered medically necessary for patients with the following findings:

Oncotype DX Breast criteria: Estrogen-receptor positive, node-negative carcinoma of the breast; estrogen-receptor positive micrometastases of carcinoma of the breast; estrogen-receptor positive breast carcinoma with 1-3 positive nodes

Prosigna - Medicare Advantage

Considered medically necessary when either of the following patient groups apply:

Prosigna criteria: ER+, lymph node-negative, stage I or II disease OR ER+, lymph node-positive (1-3 positive nodes), stage II disease

MammaPrint - Medicare Advantage

Considered medically necessary when ALL of the following are met:

MammaPrint criteria: Unilateral primary invasive breast tumor; hormone receptor–positive (ER and/or PR positive); stage T1 to T3 at high clinical risk; HER2-negative; 1-3 positive lymph nodes; test result will aid decision about adjuvant chemotherapy; patient will be treated with adjuvant endocrine therapy; ordered within 6 months after diagnosis

High clinical risk defined by tumor grade and size per policy

EndoPredict - Medicare Advantage

Considered medically necessary when ALL of the following are met:

EndoPredict criteria: Patient is post-menopausal; pathology reveals invasive ER-positive, HER2-negative carcinoma; no evidence of distant metastasis; patient is node-negative or has 1-3 positive nodes; test result will be used to determine endocrine therapy alone versus endocrine plus chemotherapy

Applies to T1-3, N0-1 disease

Oncotype DX DCIS - Medicare Advantage

Considered medically necessary when ALL of the following are met:

Oncotype DCIS criteria: Pathology (excisional or core biopsy) reveals ductal carcinoma in situ (DCIS) with no invasive disease; FFPE specimen contains at least 0.5 mm of DCIS length; test result will be used to determine surgery alone versus surgery with radiation therapy; patient is a candidate for and is considering breast-conserving surgery with or without adjuvant radiation; patient has not received and is not planning mastectomy

Insight TNBCtype - Medicare Advantage

Considered medically necessary when evaluated under the Medicare Advantage medical necessity policy:

Insight TNBCtype criteria: Insight TNBCtype may be considered medically necessary when the Medicare Advantage Plans medical necessity criteria is used for review per the Medical Necessity policy

See Related Policies section for details

Medically Necessary Assays

Covered when ALL of the following are met for the specified assays (per assay-specific clinical descriptions):

Assay-specific clinical context: Assay is used in early-stage breast cancer to provide prognostic (and where specified, predictive) information to guide adjuvant therapy decisions when interpreted with clinicopathologic factors

See individual assay descriptions for intended populations (ER/PR-positive, HER2-negative, node status, menopausal status).

Assays considered medically necessary: Breast Cancer Index OR Oncotype DX Breast OR Prosigna OR MammaPrint OR EndoPredict when their respective medical criteria are met

Each assay has its own intended population and specific ordering requirements as described in the policy.

Coverage tied to product-specific medical criteria

Assay coverage when ALL of the following are met

product_and_criteria: The assay CPT/HCPCS code is covered for Medicare Advantage Plans when the medical criteria in the Medical Necessity policy are met; the same assays/codes may be not medically necessary for Commercial Products per the policy

Coverage distinction between Medicare Advantage and Commercial Products is specified in the policy text

BluePrint is not covered due to insufficient evidence to determine clinical utility. For Medicare Advantage Plans BluePrint is explicitly listed as not covered; for Commercial Products BluePrint is listed as not medically necessary for the same reason. (See evidence statement indicating insufficient data to determine effects on health outcomes.)

For Commercial Products, use of more than one genomic expression assay to determine the necessity of adjuvant therapy (for example, ordering multiple tests such as Breast Cancer Index, Oncotype DX Breast, Prosigna, MammaPrint or EndoPredict for the same treatment decision) is considered not medically necessary because the evidence is insufficient to support clinical benefit from using multiple assays to guide adjuvant therapy.

When the policy’s specified medical criteria are not met, certain CPT/HCPCS codes listed in this policy are considered not medically necessary for Commercial Products even though those same codes may be covered for Medicare Advantage when criteria are met. Example codes referenced for product-specific coverage distinctions include 0045U and 0153U (covered for Medicare Advantage when criteria are met and not medically necessary for Commercial Products per policy text).

Benefit and eligibility determinations are governed by the member’s subscriber agreement or employer agreement, which supersede this medical policy. Providers should verify member-specific benefits and prior authorization requirements with the payer; the policy is informational and does not guarantee coverage or payment.

For Commercial Products the following tests are stated as not medically necessary: Oncotype DX Breast DCIS Score, BluePrint, and Insight TNBCtype. Additionally, use of more than one assay to determine adjuvant therapy is considered not medically necessary for Commercial Products due to insufficient evidence and potential overlap in information provided by multiple tests.

The policy explicitly lists Oncotype DX Breast DCIS Score, BluePrint, and Insight TNBCtype as not medically necessary for Commercial Products because available studies have not demonstrated sufficient precision or prospective evidence that test results change management to improve outcomes.

Specific assay CPT/HCPCS codes (examples provided in the policy) are described as not medically necessary for Commercial Products when the medical criteria are not met, even though those same codes may be covered for Medicare Advantage when criteria are satisfied. Providers should use the product-specific coverage guidance when selecting codes for submission.

Covered Indications and Clinical Context

Assays covered when specific tumor receptor status, stage, nodal status, and treatment decision-use criteria (as listed per assay) are met.

Assays covered when specific tumor receptor status, stage, nodal status, and treatment decision-use criteria (as listed per assay) are met:

assay_tumor_and_stage_criteria: Each assay is covered only when the assay-specific tumor receptor status, TNM stage, nodal status, specimen requirements (for DCIS), and intended treatment-decision use (e.g., to guide chemotherapy, radiation, or endocrine therapy extension) match the clinical criteria listed for that assay

Refer to individual assay criteria blocks for exact details

Early-stage breast cancer (assay-dependent) — examples include postmenopausal women with ER/PR-positive, HER2-negative, node-negative (or node-positive 1-3 for Prosigna/EndoPredict) disease being considered for adjuvant endocrine therapy and/or chemotherapy.

Early-stage breast cancer (assay-dependent) — examples of covered populations include:

example_populations: Postmenopausal women with ER/PR-positive, HER2-negative, node-negative disease being considered for adjuvant endocrine therapy and/or chemotherapy; and where applicable, node-positive (1-3) disease for Prosigna or EndoPredict

CPT / HCPCS Coding for Assays

Breast Cancer Index CPTCPTCovered

81518

Breast Cancer Index

Oncotype DX Breast CPTCPTCovered

81519

Oncotype DX Breast

Prosigna CPTCPTCovered

81520

Prosigna

MammaPrint CPTCPTCovered

81521

MammaPrint

EndoPredict CPTCPTCovered

81522

EndoPredict

Oncotype DX DCIS CPTCPTCovered

0045U

Oncotype DX Breast DCIS Score

Insight TNBCtype CPTCPTCovered

0153U

Insight TNBCtype

Unlisted CPT guidanceCPT

Unlisted genetic testing CPT

Use unlisted CPT when no specific CPT exists for referenced services

Breast Cancer IndexCPTCovered

81518

Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 11 genes, utilizing formalin-fixed paraffin-embedded tissue, algorithms reported as percentage risk for metastatic recurrence and likelihood of benefit from extended endocrine therapy

Oncotype DX BreastCPTCovered

81519

Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 21 genes, utilizing formalin-fixed paraffin embedded tissue, algorithm reported as recurrence score

ProsignaCPTCovered

81520

Oncology (breast), mRNA gene expression profiling by hybrid capture of 58 genes (50 content and 8 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as a recurrence risk score

MammaPrint and EndoPredictCPTCovered

81521	Oncology (breast), mRNA, microarray gene expression profiling of 70 content genes and 465 housekeeping genes, utilizing fresh frozen or formalin-fixed paraffin-embedded tissue, algorithm reported as index related to risk of distant metastasis
81522	Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 12 genes (8 content and housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as recurrence score

Oncotype DX Breast DCIS Score (Medicare Advantage coverage only)HCPCS

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

Insight TNBCtype (Medicare Advantage coverage only)HCPCS

0153U

Oncology (breast), mRNA, gene expression profiling by next-generation sequencing of 101 genes, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as triple negative breast cancer clinical subtype(s) with information on immune cell involvement

Unlisted molecular pathologyCPT

81479

Unlisted molecular pathology procedure (for tests in this policy without a specific CPT code)

Assay-specific CPT CodesCPTCovered

81521	Oncology (breast), mRNA, microarray gene expression profiling of 70 content genes and 465 housekeeping genes, utilizing fresh frozen or formalin-fixed paraffin-embedded tissue, algorithm reported as index related to risk of distant metastasis
81522	Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 12 genes (8 content and housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as recurrence score

Medicare Advantage covered HCPCS/PLA (DCIS)HCPCSCovered

0045U

Medicare Advantage covered HCPCS/PLA (TNBC subtype)HCPCSCovered

0153U

Unlisted test code (use when no specific CPT exists)CPT

81479

Unlisted molecular pathology procedure

Provider Actions, Authorization, and Billing Guidance

Prior Authorization

Prior Authorization Required / Recommended

Prior authorization is required for Medicare Advantage Plans for the listed assays. Prior authorization is recommended for Commercial Products for certain assays and can be obtained via the payer's online authorization tool for participating providers. Verify with the payer whether preauthorization is required for the member's specific plan.

Medicare Advantage: Breast Cancer Index; Oncotype DX Breast; Prosigna; MammaPrint; EndoPredict; Oncotype DX Breast DCIS Score; Insight TNBCtype
Commercial (recommended authorization): Oncotype DX Breast; Prosigna; MammaPrint; EndoPredict

Billing Rule

Code Use and Potential Prior Authorization

Specific CPT/PLA codes are identified for named assays and may be used when the medical criteria in this policy are met. Use the assay-specific CPT codes when available; if no specific CPT/PLA code exists for the service rendered, an unlisted molecular pathology code (81479) or other appropriate unlisted genetic testing CPT should be used. Note that use of a CPT/PLA code does not waive any prior authorization requirements — codes may still be subject to prior authorization.

Assay Definitions and Test Descriptions

Assays included in this policy

Assays addressedBreast Cancer Index; Oncotype DX Breast; MammaPrint; Prosigna; EndoPredict; BluePrint; Oncotype DX Breast DCIS Score; Insight TNBCtype

Platform types notedRT-PCR, microarray, and next-generation sequencing platforms referenced across assays

Specimen typesFormalin-fixed paraffin-embedded (FFPE) and fresh frozen tumor tissue (assay-dependent)

Breast Cancer Index (BCI)

Assay nameBreast Cancer Index (BCI)

MethodqRT-PCR evaluating differential expression of 11 genes plus 4 reference genes

Tests Not Covered / Not Medically Necessary

BluePrint is listed as not covered because the evidence is insufficient to determine its effects on health outcomes. This applies across Medicare Advantage Plans and Commercial Products where indicated in the policy.

Oncotype DX Breast DCIS Score, BluePrint, and Insight TNBCtype are designated as not covered / not medically necessary for Commercial Products due to insufficient evidence demonstrating clinical utility or clear impact on management decisions.

For Commercial Products, use of the assay codes listed in this policy may be considered not medically necessary when the medical criteria are not met. Additionally, ordering multiple assays to answer the same adjuvant therapy question may be denied for Commercial members.

Background — Multigene Expression Assays

Multigene expression assays measure messenger RNA expression in breast tumor tissue to estimate risk of distant recurrence and to provide prognostic (and in some cases predictive) information to guide adjuvant chemotherapy, radiation decisions for DCIS, or decisions about extended endocrine therapy. Examples addressed in this policy include assays such as the Breast Cancer Index, Oncotype DX Breast, Prosigna, MammaPrint, EndoPredict, Oncotype DX DCIS Score, BluePrint, and Insight TNBCtype.

OpenPayer

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

Coverage Criteria for Multigene Expression Assays

Covered Indications and Clinical Context

CPT / HCPCS Coding for Assays

Provider Actions, Authorization, and Billing Guidance

Assay Definitions and Test Descriptions

Tests Not Covered / Not Medically Necessary

Background — Multigene Expression Assays