CurrentEmblemHealthPolicy MG.MM.LA.39i

Gene Expression Profiling and Biomarker Testing for Breast Cancer

Defines medical necessity, limitations, and coding for multigene expression assays and select biomarker tests used to guide adjuvant chemotherapy and extended endocrine therapy decisions in early-stage breast cancer patients covered by EmblemHealth.

Policy Summary

PayerEmblemHealth

PolicyGene Expression Profiling and Biomarker Testing for Breast Cancer

Policy CodePolicy MG.MM.LA.39i

Change TypeRemoved restriction

Effective Date

Next Review DateMar 14, 2025

Key ActionSubmit clinical evidence and document a pre-test discussion when requesting preauthorization.

SourceLink

POLICY UPDATE CHANGES

Removed one-test-only coverage restriction.

5+named gene expression tests

81518-81521, 81479procedure codes

Mar 14, 2025Last review

Coverage Criteria for Gene Expression and Biomarker Testing

Preferred tests - Adjuvant chemotherapy decision

Trek Health ingests and normalizes Transparency in Coverage data and payer policy updates to give provider organizations a clear view of how commercial reimbursement behaves across markets, payers, and services. Our platform transforms raw payer disclosures into structured intelligence that supports contract evaluation, payer negotiations, and service line strategy. By combining market benchmarks with ongoing policy visibility, Trek helps teams identify variability, risk, and opportunity in commercial reimbursement. The result is faster insight, stronger negotiating positions, and more informed financial decisions.

Preferred tests (Oncotype DX, EndoPredict, Prosigna): All of the following: (1) Estrogen receptor (ER) or progesterone receptor (PGR) positive; (2) Human epidermal growth factor receptor 2 (HER2) negative; (3) Node-negative - pN0 or pN0(i+) (micrometastases < 0.2 mm in regional lymph nodes) (or member may be node-negative or node-positive when Oncotype is used, including 1-3 positive nodes for Oncotype)

Applies to Oncotype DX, EndoPredict, Prosigna

MammaPrint - Adjuvant chemotherapy decision

MammaPrint coverage: All of the following: (1) Estrogen receptor (ER) or progesterone receptor (PGR) positive; (2) HER2-negative; (3) Node negative or 1-3 local lymph nodes; (4) At high clinical risk per MINDACT trial categorization (using a modified version of Adjuvant! Online)

MammaPrint medically necessary only when all conditions met

BCI - Predictive testing for extended endocrine therapy

Breast Cancer Index (BCI) for extended endocrine therapy: All of the following: (1) Unilateral tumor; (2) Tumor size > 0.5 cm (5 mm) in greatest dimension (T1b-T3); (3) ER or PGR positive; (4) HER2-negative; (5) Node-negative or micro-metastatic node-positive with 1-3 positive nodes; (6) Clinical treatment score post-5 years> 0.5 cm (T1b-T3)

BCI considered medically necessary for predictive testing for extended endocrine therapy

Testing for clinical indications other than those specifically listed in this policy is not medically necessary. For example, gene expression profiling for non‑breast cancer indications (e.g., colon cancer) is excluded. Additional testing may be considered medically necessary only when the member has histologically distinct tumors and the medical necessity criteria for the specific assay to be used are met.

Gene expression profiling tests other than the assays listed in this policy are considered not medically necessary because there is insufficient evidence of therapeutic value. Examples of assays deemed not medically necessary include BluePrint™, H:I ratio, the Rotterdam/Veridex 76‑gene prognostic signature, HOX13:IL17BR (two‑gene signature), Mammostrat, and TargetPrint.

Applicable Procedure and Diagnosis Codes

Applicable Procedure CodesCPT | HCPCS

81479	Unlisted molecular pathology procedure.
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.
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.
81599	Unlisted multianalyte assay with algorithmic analysis [for EndoPredict].
85415	Fibrinolytic factors and inhibitors; plasminogen activator.
S3854	Gene expression profiling panel for use in the management of breast cancer treatment.

Applicable ICD-10 Diagnosis Codes (selected examples)ICD-10

C50.011	Malignant neoplasm of nipple and areola, right female breast.
C50.012	Malignant neoplasm of nipple and areola, left female breast.
C50.019	Malignant neoplasm of nipple and areola, unspecified female breast.
C50.021	Malignant neoplasm of nipple and areola, right male breast.
C50.022	Malignant neoplasm of nipple and areola, left male breast.
C50.029	Malignant neoplasm of nipple and areola, unspecified male breast.
D05.10	Intraductal carcinoma in situ of unspecified breast.
Z17.0	Estrogen receptor positive status [ER+].
Z17.1	Estrogen receptor negative status [ER-].
Z85.3	Personal history of malignant neoplasm of breast.

Tumor size threshold for BCI — > 0.5 cm (T1b-T3)

Tumor size threshold> 0.5 cm (5 mm) — T1b to T3

ApplicabilityRequired for BCI when assessing candidacy for extended endocrine therapy

MeasurementGreatest dimension of unilateral tumor

Prior Authorization, Documentation, and Submission Requirements

Prior Authorization

Preauthorization and documentation required — submission of clinical documentation for prior authorization review

Prior authorization and submission of clinical documentation are required for review. The treating physician or primary care provider must submit clinical evidence that the member meets the criteria for the requested test or treatment. Requests submitted without the required clinical evidence will not be able to be properly reviewed for prior authorization or post-payment review.

Submit relevant clinical records demonstrating the member meets policy criteria (e.g., receptor status, nodal status, tumor size, clinical risk where applicable).
Document that a pre-test discussion occurred between the provider and member, including agreement that results will be used to guide therapy.

Note

Provider actions — miscellaneous/placeholder provider action note

No additional miscellaneous provider actions are specified beyond the documentation and pre-test discussion requirements noted elsewhere in this section.

Documentation Required

Submit clinical evidence and document pre-test discussion — treating physician must submit evidence and document pre-test counseling

Treating physicians must submit clinical evidence supporting that the member meets all applicable test-specific criteria and must document that a pre-test discussion with the member occurred covering potential results and that results will be used to guide therapy.

Include documentation of ER/PR status, HER2 status, nodal status, tumor size, and clinical risk assessment where required by the specific assay.
For tests used to guide extended endocrine therapy (e.g., Breast Cancer Index), include post-5-year clinical treatment score when applicable.

Denial Risk

Documentation requirement — requests lacking submitted clinical evidence will not be properly reviewed

Requests lacking the submitted clinical evidence described above will not be properly reviewed and may be denied or subject to post-payment review.

Failure to provide required documentation may delay authorization or result in denial.
Documentation must be sufficient to demonstrate all applicable criteria for the chosen gene expression assay are met.

Background and Purpose

Gene expression profiling assays analyze tumor gene expression to estimate the risk of distant recurrence and to help guide adjuvant systemic therapy decisions in early‑stage breast cancer. These assays (for example, Oncotype DX, MammaPrint, Prosigna/PAM50, EndoPredict, and Breast Cancer Index) provide prognostic information such as risk of distant metastasis and, for some tests, predictive information about the likely benefit of adjuvant chemotherapy or of extended endocrine therapy. Specific assays use different platforms (e.g., RT‑PCR, microarray, or PCR panels), incorporate proliferation and endocrine‑signaling gene sets, and may combine molecular results with clinical tumor factors (such as tumor size) to produce a risk or recurrence score that clinicians can use in treatment decision making.

Test Definitions and Brief Descriptions

Breast Cancer Index (BCI) — PCR-based assay description

Test typePCR-based assay interrogating proliferation- and endocrine signaling–related genes

PurposeIdentifies risk of late relapse in ER+ breast cancer and potential benefit from extended hormone therapy

Patient subgroupMay identify a subset of postmenopausal women at increased risk of late relapse

EndoPredict — gene expression profile combined with clinical data

Test typeGene expression profile combined with clinical tumor and patient data

PurposeProvides decision guidance regarding the medical necessity of chemotherapy

Proprietary nameEndoPredict®

MammaPrint — 70-gene microarray test description

Test type70-gene microarray breast recurrence assay (MammaPrint®)

PurposeAssesses risk for distant metastasis (time horizon up to 10 years for patients <61; up to 5 years for ≥61)

Clinical useUsed to stratify high clinical risk for adjuvant chemotherapy decisions (per MINDACT criteria)

Oncotype DX — 21-gene assay description

Test typeMultiparameter 21-gene expression assay (Oncotype DX®) reported as a recurrence score

PurposePredicts likelihood of breast cancer recurrence and guides adjuvant tamoxifen and chemotherapy decisions

Node status allowanceMay be used when member is node-negative or node-positive (including 1–3 positive nodes) for adjuvant chemotherapy decision-making

Prosigna (PAM50) — classification and ROC description

Test typePAM50-based molecular classification (Prosigna®) providing intrinsic subtype and proliferation score

Outcome reportedRisk of Recurrence (ROR) score based on gene expression and tumor size

Clinical roleClassifies tumors by molecular profile to inform prognosis and adjuvant therapy discussions

Line of Therapy

first-line

First-line use: Use for adjuvant chemotherapy decision-making in the early-stage adjuvant setting; assays are intended to inform choice between adjuvant chemotherapy versus endocrine therapy. BCI is intended to inform extended endocrine therapy decisions after 5 years.

Applies in the early-stage, adjuvant (first-line) treatment context

Biomarker Status Requirements

ER — estrogen receptor requirement/status

RequirementER positive or PGR positive status required for coverage of listed assays

ContextApplies to preferred tests (Oncotype DX, EndoPredict, Prosigna) and MammaPrint/BCI criteria as specified

DocumentationER/PGR status must be documented in submitted clinical evidence for preauthorization review

PGR — progesterone receptor requirement/status

RequirementPGR (progesterone receptor) positive or ER positive status fulfills hormone receptor requirement for coverage

InterchangeabilityEither ER or PGR positivity meets the hormone receptor criterion across covered assays

DocumentationPGR status should be included in clinical documentation submitted for review

HER2 — HER2 negative requirement

RequirementHER2-negative status is required for coverage of the listed gene expression assays

ApplicabilitySpecified for preferred tests (Oncotype DX, EndoPredict, Prosigna), MammaPrint, and BCI

DocumentationHER2-negative result must be documented in preauthorization clinical evidence