Blue Cross Blue Shield RI gene expression coverage

Coverage Criteria for Genomic Expression Assays

Breast Cancer Index (81518)

Covered when ALL of the following are met

BCI Medical Necessity: Pathology reveals invasive carcinoma of the breast that is ER+ and/or PR+ and HER2-; patient has early-stage disease (T1-3, pN0, M0); patient is lymph node negative; patient has no evidence of distant breast cancer metastasis (non-relapsed); and test results will be used in determining treatment management for chemotherapy and/or extension of endocrine therapy.

Test is used for postmenopausal early-stage (T1-3, pN0, M0), node-negative, ER and/or PR-positive, HER2-negative patients being treated with primary adjuvant endocrine therapy; tested once per patient on FFPE primary tumor tissue.

Oncotype DX Breast (81519)

Covered when ANY of the following ER-positive settings are present

Oncotype DX eligibility: 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 lymph nodes.

Intended for use in newly diagnosed stage I-II, node-negative, ER-positive patients as described by the assay.

Prosigna (81520)

Covered when ANY of the following are met

Prosigna eligibility: ER-positive, lymph node-negative, stage I or II breast cancer; OR ER-positive, lymph node-positive (1-3 positive nodes), stage II breast cancer.

Intended for postmenopausal HR-positive patients to be treated with adjuvant endocrine therapy alone; uses the PAM50 gene signature on FFPE tissue.

MammaPrint (81521)

Covered when ALL of the following are met

MammaPrint medical necessity: Primary, invasive breast cancer that is unilateral; hormone receptor-positive (ER+ or PR+); HER2-negative; stage T1 or T2 or operable T3 at high clinical risk; one to three positive nodes; patient will be treated with adjuvant endocrine therapy; test result will aid decision regarding chemotherapy (i.e., chemotherapy is a management option); AND ordered within 6 months after diagnosis.

High clinical risk definitions (grade and tumor size) are specified in policy; MammaPrint is performed in a single laboratory on FFPE tissue.

EndoPredict (81522)

Covered when ALL of the following are met

EndoPredict medical necessity: Patient is post-menopausal; pathology reveals invasive ER-positive, HER2-negative breast carcinoma; patient is either lymph node-negative or has 1-3 positive lymph nodes; no evidence of distant metastasis; and test result will be used to determine treatment choice between endocrine therapy alone versus endocrine therapy plus chemotherapy.

Applies to T1-3, N0-1 disease; test should not be ordered if the treating physician does not intend to act on the result.

Oncotype DX Breast DCIS Score (0045U)

Covered when ALL of the following are met

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

Assay performed on FFPE DCIS tissue and reports a numerical recurrence risk score; evidence stratifies risk but clinical utility to change DCIS management is judged insufficient in some contexts.

Assay-specific intended use / coverage statements

Covered when ALL of the following are met for the named assays (per assay intent statements):

Prosigna coverage intent: Prosigna: intended as a prognostic indicator for 10-year distant recurrence-free survival in postmenopausal women with HR-positive, node-negative (stage I/II) or node-positive (1-3 nodes, stage II) breast cancer being treated with adjuvant endocrine therapy alone.

Uses the PAM50 gene signature on FFPE tumor tissue and is intended to be used with other clinicopathologic factors.

EndoPredict coverage intent: EndoPredict: intended for FFPE breast tumor tissue from postmenopausal women with early-stage (T1-3, N0-1) ER-positive, HER2-negative breast cancer (node-negative or 1-3 positive nodes) considering adjuvant endocrine therapy; identifies low-risk EPClin patients for whom the absolute benefit of chemotherapy is unlikely.

Should not be ordered if the treating physician does not intend to act upon the test result.

Oncotype DX DCIS coverage intent: Oncotype DX Breast DCIS Score: an RNA-based assay performed on FFPE DCIS tissue reporting a numerical score to stratify recurrence risk.

Coverage for molecular assays varies by product line. For BlueCHiP for Medicare, several assays including Breast Cancer Index (81518), Oncotype DX Breast (81519), Prosigna (81520), MammaPrint (81521), EndoPredict (81522), and Oncotype DX Breast DCIS Score (0045U) may be considered medically necessary when their specific medical criteria are met, while BluePrint is not covered for BlueCHiP for Medicare. For Commercial products, the list of assays considered medically necessary is similar but the policy explicitly lists BluePrint and Oncotype DX Breast DCIS Score as not medically necessary due to insufficient evidence of clinical benefit.

Providers should check the applicable product (BlueCHiP for Medicare vs. Commercial) when ordering or authorizing these assays, as coverage determinations differ and some assays are specifically excluded for certain product lines.

The policy concludes that evidence is insufficient to determine whether the Oncotype DX Breast DCIS Score or BluePrint meaningfully affect health outcomes. For the DCIS Score, studies demonstrate risk stratification into high- and low-risk groups but have not shown with sufficient precision that identified low-risk patients can safely have management (for example, omission of radiotherapy) altered. For BluePrint, the available evidence does not establish the required clinical utility to demonstrate effects on health outcomes.

Because clinical utility has not been established for these assays, the policy does not support routine changes in patient management based solely on their results.

For Commercial Products only, the use of more than one proprietary tumor gene expression assay (for example, Breast Cancer Index, Oncotype DX Breast, Prosigna, MammaPrint, or EndoPredict) to determine the necessity of adjuvant systemic therapy is considered not medically necessary. Providers should order a single assay appropriate to the clinical scenario rather than multiple concurrent prognostic tests to guide adjuvant therapy decisions.

The Oncotype DX Breast DCIS Score provides a numerical score that stratifies patients with ductal carcinoma in situ (DCIS) into different recurrence risk groups based on expression of proliferation genes, PR, GSTM1 and reference genes in FFPE DCIS tissue. However, although the test stratifies risk, current evidence is insufficient to support changing DCIS management (such as omitting radiation) based solely on the DCIS Score, because studies have not demonstrated with adequate precision that patients identified as low risk have outcomes that justify altered treatment.

Indications Considered Medically Necessary

Prognostic testing to estimate risk of distant recurrence and to guide adjuvant chemotherapy and/or extended endocrine therapy decisions in early-stage breast cancer per assay-specific criteria.

Covered indications overarching: Use of the named multigene expression assays is limited to early-stage breast cancer patients meeting the assay-specific clinical criteria below to estimate distant recurrence risk and to inform adjuvant chemotherapy and/or extended endocrine therapy decisions.

Each proprietary assay has specific specimen and clinical intent requirements as described in the individual assay criteria.

Prognostication of distant recurrence risk in early-stage, hormone receptor-positive breast cancer (postmenopausal) to inform adjuvant endocrine therapy decisions; identification of low-risk patients where chemo benefit is unlikely (EndoPredict).

CPT/HCPCS Codes and Coding Guidance

Covered CPT Code for Breast Cancer Index (81518)CPTCovered

81518

Breast Cancer Index

Covered CPT Code for Oncotype DX Breast (81519)CPTCovered

81519

Oncotype DX Breast

Covered CPT Code for Prosigna (81520)CPTCovered

81520

Prosigna

Covered CPT Code for MammaPrint (81521)CPTCovered

81521

MammaPrint

Covered CPT Code for EndoPredict (81522)CPTCovered

81522

EndoPredict

Covered CPT Code for Oncotype DX Breast DCIS Score (0045U)CPTCovered

0045U

Oncotype DX Breast DCIS Score

Unlisted genetic testingCPT

Unlisted CPT

Use for services without specific CPT code; all unlisted genetic testing CPT codes require prior authorization.

Covered CPT Codes (selected)CPTCovered

81518	Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 11 genes (7 content and 4 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithms reported as percentage risk for metastatic recurrence and likelihood of benefit from extended endocrine therapy
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
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

Covered CPT Code (MammaPrint)CPTCovered

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

Covered CPT/HCPCS and Prior Auth CodesmixedCovered

81522	Oncology (breast), mRNA, gene expression profiling by real-time RT-PCR of 12 genes (8 content and 4 housekeeping), utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as recurrence 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
81479	Unlisted molecular pathology procedure

Provider Actions, Prior Authorization, and Documentation Requirements

Prior Authorization

Prior Authorization Required / Recommended

Prior authorization is recommended for Commercial Products and required for BlueCHiP for Medicare for the assays listed in this policy. Participating providers should use the payer's online prior authorization tool where available. All unlisted genetic testing CPT codes (including 81479) require prior authorization to determine the specific service and whether it meets coverage criteria.

Commercial Products: prior authorization recommended for Breast Cancer Index; Oncotype DX Breast; Prosigna; MammaPrint; EndoPredict.
BlueCHiP for Medicare: prior authorization required for Breast Cancer Index; Oncotype DX Breast; Prosigna; MammaPrint; EndoPredict; Oncotype DX Breast DCIS Score.
Unlisted molecular pathology (CPT 81479) and other unlisted genetic testing CPTs: prior authorization required to determine service and coverage.

Denial Risk

Insufficient Evidence — Denial Risk

Tests and Uses Considered Not Medically Necessary

Not covered/Not medically necessary determinations differ by product. BluePrint is not covered for BlueCHiP for Medicare. For Commercial Products, both BluePrint and the Oncotype DX Breast DCIS Score are listed as not medically necessary because the evidence is insufficient to determine their effects on health outcomes.

Providers should verify the member's product line before submitting authorization requests, as these assays may be excluded depending on coverage rules.

The policy states that BluePrint and use of the Oncotype DX Breast DCIS Score to change clinical management are not supported because the evidence is insufficient to demonstrate clinical utility and effects on health outcomes. As a result, these assays should not be used as the sole basis for altering treatment plans.

Testing with these assays may be denied or considered not medically necessary when the intent is to change management in the absence of stronger evidence demonstrating improved health outcomes.

Assay Definitions and Test Descriptions

Breast Cancer Index (BCI) definition

Assay typeqRT-PCR molecular assay evaluating differential expression of 11 genes (7 informational, 4 reference)

Intended outputProvides individualized risk estimates for overall and late distant recurrence (BCI Score) and an H/I categorical output (High vs Low) predictive of endocrine responsiveness

Clinical useUsed in postmenopausal, early-stage (T1-3, pN0, M0), node-negative, ER and/or PR-positive, HER2-negative patients to inform chemotherapy and extended endocrine therapy decisions

SpecimenTested once per patient lifetime on FFPE primary tumor tissue obtained prior to adjuvant treatment

Genes assessed11 genes total: 7 informational (including MGI and HoxB13/IL17BR for H/I) and 4 RNA normalization (reference) genes

OpenPayer

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

Coverage Criteria for Genomic Expression Assays

Indications Considered Medically Necessary

CPT/HCPCS Codes and Coding Guidance

Provider Actions, Prior Authorization, and Documentation Requirements

Tests and Uses Considered Not Medically Necessary

Assay Definitions and Test Descriptions