BCBSRI breast gene expression coverage & prior auth

Coverage Criteria for Gene Expression Assays in Breast Cancer

Breast Cancer Index - Medical necessity

Breast Cancer Index may be considered medically necessary when ALL of the following are met:

BCI initial criteria: Pathology reveals invasive carcinoma of the breast that is ER+ and/or PR+ and HER2-; Patient has early-stage disease (T1-3, pN0-N1, M0); 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 - Medical necessity

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

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 - Medical necessity

Prosigna may be considered medically necessary when ANY of the following are met:

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

MammaPrint - Medical necessity

MammaPrint may be considered medically necessary when ALL of the following are met:

MammaPrint criteria: Unilateral primary invasive breast cancer; Hormone receptor–positive (ER+ or PR+); HER2-negative; Stage T1 or T2 or operable T3 at high clinical risk; One to three positive nodes (N1); No distant metastases; Patient will be treated with adjuvant endocrine therapy; Patient is eligible for a chemotherapy regimen containing a taxane, an anthracycline, or both; Test result will aid the patient in deciding on chemotherapy (ie, chemotherapy is a therapeutic option); Test is ordered within 6 months after diagnosis.

High clinical risk defined by grade/size criteria (see policy).

EndoPredict - Medical necessity

EndoPredict may be considered medically necessary when ALL of the following are met:

EndoPredict criteria: Patient is post‑menopausal; Pathology (excisional or biopsy) reveals invasive carcinoma of the breast that is ER‑positive and HER2‑negative; Patient is lymph node‑negative or has 1‑3 positive lymph nodes (N0‑1); 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.

Applicable for T1‑3, N0‑1 disease. Test should not be ordered if physician does not intend to act on the result.

Oncotype DX Breast DCIS Score - Medical necessity

Oncotype DX DCIS assay may be considered medically necessary when ALL of the following are met:

Oncotype DX DCIS criteria: Pathology (excisional or core biopsy) reveals ductal carcinoma in situ of the breast 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 the treatment choice between surgery alone versus surgery with radiation therapy; Patient has not received and is not planning to receive a mastectomy.

Evidence insufficiency / clinical utility statements

Summary coverage/evidence statements from the document

Tests with insufficient evidence to determine improved health outcomes: Oncotype DX Breast DCIS Score for DCIS; BluePrint molecular subtyping; Insight TNBCtype for triple‑negative breast cancer; DCISionRT; and other named assays are described as having insufficient evidence to determine effects on health outcomes or demonstrated clinical utility.

See cited evidence summaries for details.

Intended use / targeted populations

Intended use statements for specific assays

Prosigna intended use: Prosigna is intended as a prognostic indicator for 10‑year distant recurrence‑free survival in postmenopausal women with HR‑positive early‑stage breast cancer (node‑negative or 1‑3 positive nodes) to be treated with adjuvant endocrine therapy alone; the assay measures the PAM50 gene signature plus controls and housekeeping genes.

EndoPredict intended use: EndoPredict is intended for FFPE breast tumor tissue from postmenopausal women with early‑stage (T1‑3, N0‑1) ER‑positive, HER2‑negative breast cancer to identify individuals with a low EPClin score for whom the absolute benefit of adjuvant chemotherapy is unlikely to outweigh risks; the test should not be ordered if the physician does not intend to act upon the result.

For Medicare Advantage plans, BluePrint and DCISionRT are listed as not covered due to insufficient evidence to determine effects on health outcomes. For Commercial Products, BluePrint and DCISionRT are designated as not medically necessary; in addition, Insight TNBCtype and the Oncotype DX Breast DCIS Score are listed as not medically necessary for Commercial Products.

For Commercial Products ONLY, the policy specifies a multiple-test restriction: use of more than one of the listed prognostic assays (Breast Cancer Index, Oncotype DX Breast, Prosigna, MammaPrint, EndoPredict, or MammaPrint NGS) to determine the need for adjuvant chemotherapy is considered not medically necessary.

DCISionRT (CPT 0295U) is explicitly identified as not covered for Medicare Advantage Plans and not medically necessary for Commercial Products; the CPT descriptor indicates a protein IHC panel combined with clinicopathologic factors reported as a recurrence risk score.

Coverage and payment determinations remain subject to the member's subscriber agreement and any applicable employer agreement, which supersede this medical policy. Providers should verify member-specific benefits via the provider call center before ordering testing.

Named assays addressed in the policy and their coverage distinctions include: BluePrint — not covered for Medicare Advantage and not medically necessary for Commercial Products; DCISionRT (0295U) — not covered for Medicare Advantage and not medically necessary for Commercial Products; Insight TNBCtype (0153U) — considered medically necessary for Medicare Advantage when criteria are met but not medically necessary for Commercial Products; and Oncotype DX Breast DCIS Score (0045U) — covered for Medicare Advantage when criteria are met and not medically necessary for Commercial Products. Additional assays (Breast Cancer Index, EndoPredict, MammaPrint, MammaPrint NGS, Oncotype DX Breast, Prosigna) are listed with product-specific medical necessity where criteria are met.

When the specified medical criteria are met for Medicare Advantage, Oncotype DX Breast DCIS Score (0045U) and Insight TNBCtype (0153U) are covered. These same assays are stated as not medically necessary for Commercial Products in the policy.

Services that are determined to be not medically necessary (or medically necessary services that are non-covered benefits) may be denied and not payable to the provider. Providers may not bill or collect payment from members for denied services unless the member was informed and provided written agreement in advance.

Covered Indications and Use Cases

Use of listed gene expression assays to assess prognosis and guide adjuvant therapy decisions

Use of listed gene expression assays to assess prognosis and guide adjuvant therapy decisions in specified ER/PR/HER2 and stage/node‑defined breast cancer subgroups (see test‑specific criteria sets).

Top‑level covered indication: Gene expression assays listed in this policy are intended to assess prognosis and help guide adjuvant therapy decisions for members with appropriately staged and receptor‑status defined early‑stage breast cancer, per the specific test criteria below.

See individual test criteria for stage/node and receptor‑status details.

Prosigna and EndoPredict — targeted prognostic populations

Prognostic assessment of recurrence risk in postmenopausal women with HR‑positive early‑stage breast cancer (Prosigna) and identification of low‑risk ER‑positive, HER2‑negative early‑stage patients for whom chemotherapy benefit is unlikely (EndoPredict):

Prosigna/EndoPredict covered populations: Prosigna: Postmenopausal women with HR‑positive, node‑negative (stage I/II) or node‑positive (1‑3 nodes, stage II) breast cancer who will be treated with adjuvant endocrine therapy alone. EndoPredict: Postmenopausal women with early‑stage (T1‑3, N0‑1) ER‑positive, HER2‑negative breast cancer to identify low EPClin scores where adjuvant chemotherapy benefit is unlikely.

Services and Tests Considered Not Medically Necessary / Not Covered

Gene expression assays analyze mRNA expression in formalin-fixed, paraffin-embedded breast tumor tissue to provide prognostic and, in some cases, predictive information about risk of distant recurrence and potential benefit of therapies. These assays may guide decisions about adjuvant chemotherapy, radiation, or extended endocrine therapy in appropriately staged and receptor-status–defined breast cancer.

Tests explicitly designated as not covered or not medically necessary include BluePrint and DCISionRT for Medicare Advantage, and BluePrint, DCISionRT, Insight TNBCtype, and the Oncotype DX Breast DCIS Score for Commercial Products. DCISionRT (0295U) is separately listed with the CPT code and descriptor as not covered. Providers should confirm benefits and obtain any required authorizations to avoid denial and potential member liability.

Coding, CPT/HCPCS/PLA Mappings and Billing Notes

Covered CPT Codes (examples listed)CPTCovered

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 Codes (examples listed)CPTCovered

0153U

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

Unlisted genetic testing codesCPT

Unlisted CPT codes

Use an Unlisted CPT code when a specific CPT code is not available for the referenced genetic/molecular test; all unlisted genetic testing CPT codes require prior authorization to determine the service and coverage

Covered CPT Codes (examples)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

Covered CPT CodesCPTCovered

81520

Covered 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

Covered CPT CodesCPTCovered

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

Covered CPT CodesCPTCovered

81523

Oncology (breast), mRNA, next-generation sequencing gene expression profiling of 70 content genes and 31 housekeeping genes, utilizing formalin-fixed paraffin-embedded tissue, algorithm reported as index related to risk to distant metastasis (Code Effective 1/1/2022)

Covered CPT Codes for Medicare Advantage (not commercially)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

Covered CPT Codes for Medicare Advantage (not commercially)CPTCovered

0153U

Not covered CPT CodesCPTNot Covered

0295U

Oncology (breast ductal carcinoma in situ), protein expression profiling by immunohistochemistry of 7 proteins with 4 clinicopathologic factors (size, age, margin status, palpability), utilizing formalin-fixed paraffin-embedded (FFPE) tissue, algorithm reported as a recurrence risk score - not covered / not medically necessary

Prior authorization requiredCPT

81479	Unlisted molecular pathology procedure — used for any test in this policy that does not have a specific CPT code; requires prior authorization for Medicare Advantage Plans and Commercial Products
Unlisted CPT codes	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

DCISionRT risk threshold — study context

DCISionRT study-context thresholdScore <3 classified as low risk (used in Simon et al. 2009 category B study showing no radiation benefit in low-risk group)

Score interpretationDCISionRT stratifies DCIS into three risk groups: low risk, elevated risk with good response, and elevated risk with poor response

Purpose of thresholdThreshold <3 was used to identify individuals for whom radiation provided no observed benefit in the cited retrospective validation

Provider Actions, Authorization and Billing Guidance

Prior Authorization

Prior Authorization Required

Prior authorization is required for Medicare Advantage Plans for the specified molecular/genetic tests; prior authorization is recommended for Commercial Products. Providers must verify member-specific benefits and obtain prior authorization where required before ordering services.

Medicare Advantage Plans: prior authorization required for listed tests.
Commercial Products: prior authorization recommended for listed tests.
81479 (Unlisted molecular pathology) requires prior authorization when used for any test in this policy without a specific CPT code.

Billing Rule

Unlisted Codes and Authorization Process

All unlisted genetic testing CPT codes (including 81479 when applicable) require prior authorization so the plan can determine the specific service rendered and whether it is a covered, medically necessary service. Laboratories are not permitted to obtain authorizations on behalf of ordering physicians; only the ordering physician may initiate and participate in authorization, appeals, or other administrative processes.

Definitions of Tests and Terms

Breast Cancer Index (BCI) — definition and assay details

Assay descriptionMolecular qRT-PCR assay evaluating expression of 11 genes (7 informative genes and 4 normalization genes)

OutputsProvides individualized BCI Score (percent risk of distant recurrence overall and late DR) and H/I categorical output (High vs Low) for likelihood of endocrine response

Intended populationPostmenopausal women with early-stage (T1-3, pN0-N1, M0), ER and/or PR-positive, HER2-negative breast cancer receiving adjuvant endocrine therapy

Specimen requirementsTested once per patient lifetime on FFPE tissue from the primary tumor obtained prior to adjuvant treatment

Oncotype DX Breast — definition and assay details

Assay description

Eligibility Requirements and Member Scope

Eligibility for coverage under this policy requires that the applicable medical necessity criteria for the specific assay be met and that the test be used to inform treatment decisions as described in the test‑specific sections. The policy does not require prior genetic testing; instead, it directs use based on the clinical criteria for each assay.

Background and Clinical Context

Background: these multigene assays measure expression of multiple genes in FFPE breast tumor tissue to produce prognostic scores and, for some assays, predictive information to inform adjuvant treatment decisions. Results are intended to assist clinicians and patients in weighing the benefits and risks of chemotherapy, radiation, or extended endocrine therapy in defined clinical scenarios.

OpenPayer

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

Coverage Criteria for Gene Expression Assays in Breast Cancer

Covered Indications and Use Cases

Services and Tests Considered Not Medically Necessary / Not Covered

Coding, CPT/HCPCS/PLA Mappings and Billing Notes

Provider Actions, Authorization and Billing Guidance

Definitions of Tests and Terms

Eligibility Requirements and Member Scope

Background and Clinical Context