Notification



Notification Issue Date:



Medical Policy Bulletin


Title:Assays of Genetic Expression in Tumor Tissue for Breast Cancer Prognosis (Independence Administrators)

Policy #:06.02.27l

This policy is applicable to the Company’s commercial products only. Policies that are applicable to the Company’s Medicare Advantage products are accessible via a separate Medicare Advantage policy database.


The Company makes decisions on coverage based on Policy Bulletins, benefit plan documents, and the member’s medical history and condition. Benefits may vary based on contract, and individual member benefits must be verified. The Company determines medical necessity only if the benefit exists and no contract exclusions are applicable.

When services can be administered in various settings, the Company reserves the right to reimburse only those services that are furnished in the most appropriate and cost-effective setting that is appropriate to the member’s medical needs and condition. This decision is based on the member’s current medical condition and any required monitoring or additional services that may coincide with the delivery of this service.

This Medical Policy Bulletin document describes the status of medical technology at the time the document was developed. Since that time, new technology may have emerged or new medical literature may have been published. This Medical Policy Bulletin will be reviewed regularly and be updated as scientific and medical literature becomes available. For more information on how Medical Policy Bulletins are developed, go to the About This Site section of this Medical Policy Web site.



Policy

Coverage is subject to the terms, conditions, and limitations of the member's contract.


This policy only applies to members for whom Independence Administrators serves as the claims administrator. For all other Independence members, refer to the policy entitled eviCore Lab Management Program.

The intent of this policy is to communicate the coverage positions for assays of genetic expression in tumor tissue for breast cancer prognosis.

For information on policies related to this topic, refer to the Cross References section in this policy.

MEDICALLY NECESSARY

The Oncotype DX® or MammaPrint® test is considered medically necessary and, therefore, covered for individuals with primary, invasive stage I or stage II breast cancer when the test is ordered within six months of a primary breast cancer diagnosis, test results are expected to have significant clinical value by helping the individual decide for or against chemotherapy, clinical documentation indicates that the test results are expected to play a significant clinical role in the evaluation of the individual's prognosis, AND all of the criteria for the specific test are met:

ONCOTYPE DX®
  • The individual is a candidate for possible adjuvant chemotherapy such as tamoxifen or aromatase inhibitors (ie, chemotherapy is not precluded due to other factors such as advanced age and/or significant comorbidities ), and testing is being done specifically to guide the decision as to whether or not adjuvant chemotherapy will be used.
  • The breast cancer is nonmetastatic (node negative) or with 1-3 involved ipsilateral axillary lymph nodes.
  • The breast tumor is unilateral and non-fixed (ie, tumor does not adhere to the chest wall).
  • The breast tumor is hormone receptor--positive, (ie, estrogen-receptor positive or progesterone-receptor positive).
  • The breast tumor is human epidermal growth factor--receptor 2 (HER2) negative.
  • The breast tumor size is 0.6 to 1 cm with moderate/poor differentiation or unfavorable features OR tumor size is larger than 1 cm.
  • The breast tumor is sentinel lymph node--negative by hematoxylin and eosin (H&E) staining, even if immunoassay is positive for sentinel lymph node; OR the breast tumor has axillary node micrometastasis, which is no greater than 2.0 millimeters (mm) in size.

MAMMAPRINT®
  • Chemotherapy has not been initiated.
  • The individual is Tamoxifen independent (ie, the individual has not received Tamoxifen therapy) at the time of MammaPrint® testing, but the individual is a candidate for possible adjuvant chemotherapy (ie, chemotherapy is not precluded due to other factors advanced age and/or significant comorbidities ),
  • The breast cancer is nonmetastatic.
  • The tumor size is less than or equal to 5.0 centimeters (cm).
  • The breast tumor is sentinel lymph node--negative and/or any nodal micrometastases are no greater than 2.0 millimeters (mm) in size.

In cases where there are multiple primary breast tumors, MammaPrint® may be medically necessary and, therefore, covered if each primary breast tumor separately meets the criteria listed above. If multiple breast tumors meet the eligibility criteria, the Recurrence Score (RS) from one tumor must be determined before subsequent testing of another tumor.

PROSIGNA BREAST CANCER PROGNOSTIC GENE SIGNATURE ASSAY / PAM50 BREAST CANCER INTRINSIC SUBTYPE CLASSIFIER

PROSIGNA™ breast cancer prognostic gene signature assay / PAM50 Breast Cancer Intrinsic Subtype Classifier is considered medically necessary and, therefore, covered for individuals with invasive breast cancer with no regional lymph node metastasis, and for whom chemotherapy is a treatment option; and results from this Prosigna test will be used in making chemotherapy treatment decisions when all of the following tumor specific criteria are met:
  • Tumor size >0.4cm (4mm) in greatest dimension (T1b-T3), and
  • Hormone receptor positive (ER+/PR+), and
  • HER2 negative

When more than one breast cancer primary is diagnosed, there should be reasonable evidence that the tumors are distinct (e.g., bilateral, different quadrants, different histopathologic features, etc.), and there should be no evidence from either tumor that chemotherapy is indicated with or without knowledge of the Prosigna test result (e.g., histopathologic features or previous Gene Expression Assay result of one tumor suggest chemotherapy is indicated). If both tumors are to be tested, both tumors must independently meet the required clinical characteristics outlined above.

NOT MEDICALLY NECESSARY

There should be no repeat Prosigna testing performed on the same sample when a result was successfully obtained by using Prosigna or any other test in this category.


EXPERIMENTAL/INVESTIGATIONAL

All other indications for the 21-gene RT-PCR assay (i.e., Oncotype DX®), the 70-Gene Signature assay (i.e., MammaPrint®), and PROSIGNA™ breast cancer prognostic gene signature assay / PAM50 Breast Cancer Intrinsic Subtype Classifier, including determination of recurrence risk in individuals with invasive breast cancer with positive lymph nodes or individuals with bilateral disease, are considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

Use of a subset of genes from the 70-Gene Signature (i.e., MammaPrint®), or the 21-gene RT-PCR assay for predicting recurrence risk in individuals with noninvasive ductal carcinoma in situ (i.e., Oncotype DX® DCIS) to inform treatment planning after excisional surgery are considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

All other gene expression assays for breast cancer prognosis (e.g., Mammostrat® Breast Cancer Test, the Breast Cancer IndexSM, BreastOncPx™, NexCourse® Breast IHC4, BreastPRS™, and EndoPredict™) for any indication are considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

The use of gene expression assays in men with breast cancer is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

The use of gene expression assays to molecularly subclassify breast cancer (eg, BluePrint®) is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

The use of gene expression assays for quantitative assessment of ER, PR, and HER2 overexpression (eg, TargetPrint®) is considered experimental/investigational and, therefore, not covered because the safety and/or effectiveness of this service cannot be established by review of the available published peer-reviewed literature.

REQUIRED DOCUMENTATION

The individual's medical record must reflect the medical necessity for the care provided. These medical records may include, but are not limited to: records from the professional provider's office, hospital, nursing home, home health agencies, therapies, and test reports.

The Company may conduct reviews and audits of services to our members, regardless of the participation status of the provider. All documentation is to be available to the Company upon request. Failure to produce the requested information may result in a denial for the service.

The laboratory and/or the ordering health care professional's documentation should indicate that the individual has cancer of the breast that is hormone receptor--positive and node-negative among meeting other clinical criteria for medically necessary testing. In addition, prior to ordering the test, the ordering health care professional's documentation should indicate that the intention to treat or not treat with adjuvant chemotherapy would be contingent, at least in part, on the results of the test for the individual in question and would play a significant role in management of the individual. For example, an individual with a large, high-grade cancer who, in agreement with the oncologist, has decided to have adjuvant chemotherapy, regardless of the results of the test, would not be an appropriate candidate for this test.
Guidelines

(Key: +, positive; –, negative; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; Ki67, the protein encoded by the MKI67 gene that is often used a measure of cellular proliferation; PR, progesterone receptor; pt(s); patient(s); RS, Recurrence Score; tx, treatment or therapy)

ONCOTYPE DX® ASSAY

The National Comprehensive Cancer Network (NCCN) guidelines indicate that, in individuals who have N–, ER+ or PR+, HER2– primary breast cancer with ductal, lobular, mixed, or metaplastic histology, the Oncotype DX® assay may be an option for evaluation of individuals with T1, T2, or T3 primary tumors that are > 0.5 cm in size. The treatment recommendations according to the results of the Oncotype DX® assay are:
  • Oncotype DX® assay not performed: Adjuvant endocrine therapy with possibly adding adjuvant chemotherapy.
  • Low-risk (RS < 18): Adjuvant endocrine therapy only.
  • Intermediate-risk (RS 18 to 30): Adjuvant endocrine therapy with possibly adding adjuvant chemotherapy.
  • High-risk (RS ≥ 31): Adjuvant endocrine therapy with adjuvant chemotherapy.

MAMMAPRINT® ASSAY

Data have indicated that it is feasible to include the MammaPrint® assay in clinical practice and, if used, may result in 40% of individuals having different treatment options compared with the St. Gallen guidelines.

St. Gallen Criteria for Offering Chemotherapy:
  • HER2+ (prior to, or in combination, w/ anti-HER2 treatment trastuzumab [Herceptin])
  • Triple-negative disease (ER–, PR–, HER2–)
  • ER+, HER2– disease depends on risk:
    • Suggestive for chemotherapy (high risk of recurrence): Lower ER and PR levels; grade 3 histology; high proliferation rate (through Ki67 index); N+ w/ ≥4 nodes involved; extensive peritumoral vascular invasion; tumor size >5 cm; individual’s preference to use all available treatments; high RS score.
    • Suggestive for antiestrogen treatment alone (low risk of recurrence): Higher ER and PR levels; grade 1 histology; low proliferation rate (using Ki67 index); N–; absence of extensive peritumoral vascular invasion; tumor size ≤2 cm; individual’s preference to avoid chemotherapy adverse effects; low RS score.
    • Factors not useful in making a decision to use adjuvant chemotherapy: Grade 2 histology; intermediate proliferation rate (using Ki67); N+ w/ 1-3 nodes, tumor size 2.1-5 cm; an intermediate RS score.
    • Individuals with tumor size <1 cm may not need adjuvant chemotherapy.

PROSIGNA™ BREAST CANCER PROGNOSTIC GENE SIGNATURE ASSAY

Please see the description section of this policy for Prosigna.

BENEFIT APPLICATION

Subject to the terms and conditions of the applicable benefit contract, assays of genetic expression in tumor tissue using the Oncotype DX® and MammaPrint® testing are covered under the medical benefits of the Company’s products when the medical necessity criteria listed in this medical policy are met.

However, services that are identified in this policy as experimental/investigational are not eligible for coverage or reimbursement by the Company.

The Company’s laboratory network has extensive genetic testing capabilities; therefore, providers should refer members only to participating laboratories for covered services. In the unusual circumstance that a specific covered test and related services are not available through a participating laboratory, providers must contact the Company to obtain preapproval.

Members who have out-of-network benefits may choose to use a non-participating laboratory for a medically necessary service, but they will have greater out-of-pocket costs associated with that service. In addition, the member will be financially responsible for the entire cost of any service that is non-covered (e.g., a service that is considered experimental/investigational).

US FOOD AND DRUG ADMINISTRATION (FDA) STATUS

MammaPrint® was U.S. Food and Drug Association (FDA)--approved on February 6, 2007. MammaPrint® is performed in Agendia laboratories in the Netherlands and in California.

Prosigna™ / PAM50 Breast Cancer Intrinsic Subtype Classifier received 510(k) clearance from FDA based on substantial equivalence to MammaPrint® on September 6, 2013.

Other tests mentioned in this policy, including the Oncotype DX® test, are offered as laboratory-developed tests under Clinical Laboratory Improvement Amendments (CLIA)‒licensed laboratories. Clinical laboratories may develop and validate tests in-house and market them as a laboratory service; laboratories offering such tests as a clinical service must meet general regulatory standards of CLIA and must be licensed by CLIA for high complexity testing.

Description

According to the American Cancer Society (ACS), breast cancer is the most common cancer among women (other than skin cancer) and is the second leading cause of cancer death in women, after lung cancer. Early detection of the disease by mammography is especially valuable because it increases treatment options and saves lives. Factors that increase the risk of breast cancer include personal or family history of breast cancer, biopsy-confirmed atypical hyperplasia, significant mammographic breast density, an irregular menstrual history, recent use of oral contraceptives, giving birth for the first time after 30 years of age, never giving birth, obesity after menopause, postmenopausal hormone therapy, or consumption of one or more alcoholic beverages per day.

Taking into account the medical circumstances and an individual's preference, treatment options may involve a lumpectomy (local removal of the tumor) or mastectomy (surgical removal of the breast). Treatment may also include the removal of axillary lymph nodes if the cancer has spread to these nodes. Radiation therapy, chemotherapy, and hormone therapy are adjuvant post-surgical treatment options that are used to prevent recurrence of the cancer and/or progression of the disease. Typically, two or more of these methods are used.

Prognosis in breast cancer is currently based on an individual's age, tumor size, histology, status of the axillary lymph nodes, histologic type, and hormone receptor status. The subset of women with breast cancer who would benefit from adjuvant chemotherapy, radiation therapy, or hormone therapy after surgery is unclear. Individuals with the same set of risk factors can have markedly different prognoses. For example, not all women with positive axillary lymph nodes are destined to progress to metastatic disease, yet adjuvant chemotherapy is routinely recommended in these cases. According to the ACS, providers generally recommend adjuvant therapy for women with a tumor larger than 1 cm or if the cancer has spread to the lymph nodes. Currently, there are no exclusive risk factors that would improve individual selection criteria for adjuvant therapy or other breast cancer treatments.

Laboratory tests have been developed that detect the expression, via messenger ribonucleic acid (mRNA) or protein, of many different genes in breast tumor tissue and combine the results into a prediction of distant recurrence risk for women with early stage breast cancer. Test results may help providers and individuals decide whether to include adjuvant chemotherapy in postsurgical management.

For women with early-stage, invasive breast cancer (ie, cancer extending beyond the basement membrane of the mammary ducts into adjacent tissue), adjuvant chemotherapy provides the same proportional benefit regardless of prognosis. However, the absolute benefit of chemotherapy depends on the baseline risk of recurrence. For example, women with the best prognosis have small tumors, are estrogen receptor (ER)--positive, and lymph node--negative. These women have an approximately 15% baseline risk of recurrence; approximately 85% of these individuals would be disease-free at 10 years with tamoxifen treatment alone and could avoid the toxicity of chemotherapy, if they could be accurately identified. Conventional risk classifiers (eg, Adjuvant! Online) estimate recurrence risk by considering criteria such as tumor size, type, grade, and histologic characteristics; hormone receptor status; and lymph node status. However, no single classifier is considered a criterion standard, and several common criteria have qualitative or subjective components that add variability to risk estimates. As a result, more individuals are treated with chemotherapy than can benefit. Better predictors of baseline risk could help women, who prefer to avoid chemotherapy if assured that their risk is low, make better treatment decisions in consultation with their healthcare providers.

GENE EXPRESSION TESTS FOR BREAST CANCER PROGNOSIS

Recently, several manufacturers have identified panels of gene expression markers (“signatures”) that appear to predict the baseline risk of invasive breast cancer recurrence after surgery, radiotherapy, and endocrine therapy (for hormone receptor-positive tumors). Several gene expression tests commercially available in the U.S. include 21-Gene Recurrence Score (Oncotype DX®), 70-Gene Signature (MammaPrint®), Breast Cancer IndexSM, Mammostrat® Breast Cancer Test, BreastOncPx™, NexCourse® Breast IHC4, Prosigna™/ PAM50 Breast Cancer Intrinsic Subtype Classifier, BreastPRS™, and EndoPredict™. If these panels are more accurate risk predictors than current conventional classifiers, they could be used to aid chemotherapy decision making when current guidelines do not strongly advocate chemotherapy, without negatively affecting disease-free and overall survival (OS).

Current National Comprehensive Cancer Network (NCCN) guidelines for breast cancer (version 3.2014) do not include recommendations for any gene expression signature tests. However, NCCN states that Oncotype DX® may be considered as an option when evaluating individuals who have invasive breast cancer with all of the following features:

Category 2A recommendation:
  • Hormone receptor-positive
  • HER2-negative
  • Node-negative OR not greater than 2 mm axillary node metastasis AND
  • Tumor size 0.6 to 1.0 cm with unfavorable features OR larger than 1 cm

The NCCN Guideline Panel emphasized that Oncotype DX® recurrence score should be used for decision making only in the context of other elements of risk stratification for an individual.

21-GENE RECURRENCE SCORE (ONCOTYPE DX®)

The 21-Gene Recurrence Score (Oncotype DX®) assay is supported by strong evidence of clinical validity, ie, that the recurrence score (RS) is strongly associated with risk of distant recurrence in women with invasive breast cancer that is positive for hormone receptors, negative for HER2, and without lymph node involvement. Limited but sufficient evidence supports analytic validity and clinical utility in this population. Oncotype DX® adds additional risk information to conventional clinical classification of high-risk individuals and identifies a subset of individuals who would otherwise be recommended for chemotherapy but who are actually at lower risk of recurrence (average 7% to 9% risk at 10 years; upper 95% confidence interval limits, 11% to 15%). Prior to testing, the individual and provider should discuss the potential results of the test and agree to use the results to guide therapy (ie, the individual will forgo adjuvant chemotherapy if Oncotype DX score is low. Thus, a woman who prefers to avoid the toxicity and inconvenience of chemotherapy and whose Oncotype DX® RS value shows that she is at very low risk of recurrence might reasonably decline chemotherapy.

In similar women who are node-positive, evidence is less clear that the risk of recurrence in low-risk RS individuals is sufficiently low or that the benefit of chemotherapy is insufficiently large, to recommend avoiding otherwise currently recommended treatment. Additional studies are necessary and ongoing. For women with ductal carcinoma in situ (DCIS), development and conductance of high-quality and robust clinical validity studies are needed to allow full evaluation of a subset of genes from the 21-gene recurrence score (ie, Oncotype DX® DCIS) to predict recurrence and inform treatment planning post-excision. Moreover, no information is yet available on whether women are better categorized as to their recurrence risk by the Oncotype DX® DCIS Score compared with standard clinical risk indicators.

Guidelines from the National Comprehensive Cancer Network (NCCN, 2015) state that "the 21-gene RT-PCR assay recurrence score can be considered in select patients with 1-3 involved ipsilateral axillary lymph nodes (ALN) to guide the addition of combination chemotherapy to standard hormone therapy. A retrospective analysis of a prospective randomized trial suggests that the test is predictive in this group similar to its performance in node-negative disease.” The NCCN guidelines (2015) explained: “Unplanned, retrospective subset analysis from a single randomized clinical trial in post-menopausal, ALN-positive, ER-positive breast cancer found that the 21-gene RT-PCR assay may provide predictive information for chemotherapy in addition to tamoxifen [citing Albain, et al., 2010]. Patients with a high score in the study benefited from chemotherapy, whereas patients with a low score did not appear to benefit from the addition of chemotherapy regardless of the number of positive lymph nodes. Patient selection for assay use remains controversial.” “The RxPONDER trial will confirm the SWOG-8814 trial data for women with ER-positive, node-positive disease treated with endocrine therapy with or without chemotherapy based on risk scores.”

70-GENE SIGNATURE (MAMMAPRINT®)

In the United States, the MammaPrint® assay is intended for individuals with breast cancer who are stage I or II, are node negative (N–), and have a tumor size < 5.0 centimeters (cm). The breast cancer can be ER-positive or ER-negative. When the test was first introduced, there was a requirement that individuals be < 61 years of age; however, that requirement has now been removed from the Food and Drug Administration (FDA) labeling. Outside of the United States, individuals may be node positive (N+) with up to three affected nodes.

The analytical validity of the MammaPrint® assay using fresh frozen tissue has been well defined as the assay has received FDA clearance. The results of studies indicate the assay has low variability in repeated analyses of the same tumor samples; similar results were found in analysis of fresh frozen samples and samples stored in an RNA fixative solution; and there was good agreement between samples analyzed at the two Agendia laboratories in the Netherlands and California. No published studies are available investigating the analytical validity or clinical validity of the commercially marketed MammaPrint® test using formalin-fixed paraffin-embedded (FFPE) tissue. With regards to clinical validity, a number of studies using previously collected tumor samples have validated the MammaPrint® assay. Data have indicated that it is feasible to include the MammaPrint® assay in clinical practice and, if used, may result in 40% of individuals having different treatment options compared with the St. Gallen guidelines (see the Guidelines section of this policy document). Two publications based on the prospective “Microarray Prognostics in Breast Cancer” (RASTER) study provided some evidence of clinical utility of MammaPrint, as some participating individuals changed therapies based upon results of the test. Currently ongoing is the “Microarray in Node-Negative Disease May Avoid Chemotherapy” (MINDACT) study, which is investigating the clinical utility of the fresh frozen MammaPrint® assay; however, results will not be available for several more years. Until the results of this study are available, definition of the clinical utility of the MammaPrint® assay remains limited.

PROSIGNA™ BREAST CANCER PROGNOSTIC GENE SIGNATURE ASSAY

Prosigna is a gene expression test designed to predict the chance of 10 year recurrence of breast cancer. Prosigna is indicated in post-menopausal women with hormone receptor positive, node negative (Stage I or II) or node positive (Stage II), early stage breast cancer. This assay is intended to assist patients and providers considering treatment with adjuvant chemotherapy. Prosigna is based on the 50 gene expression signature called PAM50. This assay uses RNA from formalin fixed paraffin embedded (FFPE) samples to calculate a risk score. The algorithm used for the Prosigna score uses the 50-gene expression profile in combination with clinical variables to classify breast cancer into one of the following four types: Luminal A, Luminal B, HER2-enriched, and Basal-like. A risk of recurrence (ROR) score is also calculated using gene expression and clinical variables. This ROR score is reported as 0-100 and reflects the probability of disease recurrence at 10 years. A ROR score of 1-10 corresponds to a 10 year distant recurrence of 0%. This risk increases to approximately 15% and then 33.3% when the ROR score reaches 61-70 and 91-100, respectively.

Evidence-based clinical guidelines from the American Society of Clinical Oncology (ASCO) 2016 state:
  • “If a patient has ER/PgR-positive, HER2-negative (node-negative) breast cancer, the clinician may use the PAM50 risk of recurrence (ROR) score (Prosigna Breast Cancer Prognostic Gene Signature Assay; NanoString Technologies, Seattle, WA), in conjunction with other clinicopathologic variables, to guide decisions on adjuvant systemic therapy. Type: evidence based. Evidence quality: high. Strength of recommendation: strong.”
  • “If a patient has ER/PgR-positive, HER2-negative (node-positive) breast cancer, the clinician should not use the PAM50-ROR to guide decisions on adjuvant systemic therapy. Type: evidence based. Evidence quality: intermediate. Strength of recommendation: moderate.”
  • “If a patient has HER2-positive breast cancer, the clinician should not use the PAM50-ROR to guide decisions on adjuvant systemic therapy. Type: informal consensus. Evidence quality: insufficient. Strength of recommendation: strong.”
  • “If a patient has TN breast cancer, the clinician should not use the PAM50-ROR to guide decisions on adjuvant systemic therapy. Type: informal consensus. Evidence quality: insufficient. Strength of recommendation: strong.”

BREAST CANCER INDEXSM, MAMMOSTRAT® BREAST CANCER TEST, BREASTONCPX, NEXCOURSE® Breast IHC4, BREASTPRS™, ENDOPREDICT™

Evidence supporting these tests comprises clinical validity data showing that these tests are independently and significantly associated with distant recurrence and that the tests can identify a lower risk population of women with early, invasive breast cancer who may not need chemotherapy. In almost all cases, these tests are not added to and compared with a standard clinicopathologic classifier such as Adjuvant! Online. The BreastOncPx™ validation study included a receiver operating characteristic (ROC) curves analysis comparing the test with Adjuvant! Online, but no clear evidence supporting clinical utility was available. NexCourse® Breast IHC4 (immunohistochemical markers) was compared with standard clinicopathological prognostic classifiers in a reclassification analysis and was shown to accurately reclassify significant numbers of individuals from high and intermediate risk to low risk, but sample size was small and insufficient for conclusions.

No published literature on the use of gene expression profiling in men with breast cancer was identified.

BLUEPRINT® AND TARGETPRINT®

Gene expression patterns have led to the identification of molecular subtypes of breast cancer, which have different prognoses and responses to treatment regimens. These molecular subtypes are largely distinguished by differential expression of estrogen receptors (ER), progesterone receptors (PR), and human epidermal growth factor receptor 2 (HER2) in the tumor, and are classified as luminal, basal, or HER2 type. Luminal type breast cancers are ER-positive; basal type breast cancers correlate best with ER-, PR-, and HER2-negative (“triple negative”) tumors, and HER2 type, with high expression of HER2.

At present, methodology for molecular subtyping is not standardized, and breast cancer subtyping is routinely assessed by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).

BluePrint® is an 80-gene expression assay that classifies breast cancer into basal type, luminal type, or HER2-type. The test is marketed as an additional stratifier into a molecular subtype after risk assessment with MammaPrint®.

TargetPrint® is a microarray-based gene expression test that offers a quantitative assessment of ER, PR, and HER2 overexpression in breast cancer. The test is marketed to be used in conjunction with MammaPrint® and BluePrint®.

The 80-gene expression assay BluePrint® discriminates among three breast cancer molecular subtypes, and TargetPrint® is a method to measure ER, PR, and HER2 as an alternative to immunohistochemistry and FISH. Clinical utility of BluePrint® is unknown, as it is unclear how this test will add to treatment decision making using currently available, accepted methods (eg, clinical and pathologic parameters). The incremental benefit of using TargetPrint® as an alternative to current standard methods of measuring ER, PR, and HER2 has not been demonstrated, nor is it included in recommendations for testing issued by the American Society of Clinical Oncology (ASCO) and the College of American Pathologists.
References


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Dowsett M, Cuzick J, Wale C, et al. Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study. J Clin Oncol 2010; 28(11):1829-34.

Dowsett M, Houghton J, Iden C, et al. Benefit from adjuvant tamoxifen therapy in primary breast cancer patients according oestrogen receptor, progesterone receptor, EGF receptor and HER2 status. Ann Oncol 2006; 17(5):818-26.

Dowsett M. on Behalf of the ATAC Trialists Group. Analysis of time to recurrence in the ATAC (arimidex, tamoxifen, alone or in combination) trial according to estrogen receptor and progesterone receptor status. Twenty-sixth Annual San Antonio Breast Cancer Symposium 2003.

Dowsett M, Sestak I, Lopez-Knowles E, et al. Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy. J Clin Oncol 2013; 31(22):2783-90.

Drukker CA, Bueno-de-Mesquita JM, Retel VP, et al. A prospective evaluation of a breast cancer prognosis signature in the observational RASTER study. Int J Cancer 2013; 133(4):929-36.

Drukker CA, Nijenhuis MV, Bueno-de-Mesquita JM, et al. Optimized outcome prediction in breastcancer by combining the 70-gene signature with clinical risk prediction algorithms. Breast Cancer Res Treat 2014; 145(3):697-705.

Drukker CA, van Tinteren H, Schmidt MK, et al. Long-term impact of the 70-gene signature on breast cancer outcome. Breast Cancer Res Treat 2014; 143(3):587-92.

Dubsky P, Brase JC, Jakesz R, et al. The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients. Br J Cancer 2013; 109(12):2959-64.

Early Breast Cancer Trialists' Collaborative G. Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. Lancet 2011; 378(9793):771-84.

Espinosa E, Vara JA, Redondo A, et al. Breast cancer prognosis determined by gene expression profiling: a quantitative reverse transcriptase polymerase chain reaction study. J Clin Oncol 2005; 23(29):7278-85.

Esserman LJ, Berry DA, Cheang MC, et al. Chemotherapy response and recurrence-free survival in neoadjuvant breast cancer depends on biomarker profiles: results from the I-SPY 1 TRIAL (CALGB150007/150012; ACRIN 6657). Breast Cancer Res Treat 2012; 132(3):1049-62.

Fan C, Oh DS, Wessels L, et al. Concordance among gene-expression-based predictors for breast cancer. N Engl J Med 2006; 355(6):560-9.

Filipits M, Nielsen TO, Rudas M, et al. The PAM50 risk-of-recurrence score predicts risk for late distant recurrence after endocrine therapy in postmenopausal women with endocrine-responsive early breast cancer. Clin Cancer Res 2014; 20(5):1298-305.

Fried G, Moskovitz M. Treatment decisions in estrogen receptor-positive early breast cancer patients with intermediate oncotype DX recurrence score results. SpringerPlus 2014; 3:71.

Gennari A, Sormani MP, Pronzato P, et al. HER2 status and efficacy of adjuvant anthracyclines in early breast cancer: a pooled analysis of randomized trials. J Natl Cancer Inst 2008; 100(1):14-20.

Gianni L, Zambetti M, Clark K, et al. Gene expression profiles in paraffin-embedded core biopsy tissue predict response to chemotherapy in women with locally advanced breast cancer. J Clin Oncol 2005; 23(29):7265-77.

Glas AM, Floore A, Delahaye LJ, et al. Converting a breast cancer microarray signature into a high throughput diagnostic test. BMC Genomics 2006; 7:278.

Gnant M, Filipits M, Greil R, et al. Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone. Ann Oncol 2014; 25(2):339-45.

Goetz MP, Suman VJ, Ingle JN, et al. A two-gene expression ratio of homeobox 13 and interleukin-17B receptor for prediction of recurrence and survival in women receiving adjuvant tamoxifen. Clin Cancer Res 2006; 12(7 Pt 1):2080-7.

Goldhirsch A, Winer EP, Coates AS, et al. Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 2013; 24(9):2206-23.

Goldstein LJ, Gray R, Badve S, et al. Prognostic utility of the 21-gene assay in hormone receptor positive operable breast cancer compared with classical clinicopathologic features. J Clin Oncol 2008; 26(25):4063-71.

Habel LA, Shak S, Jacobs MK, et al. A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res 2006; 8(3):R25.

Haibe-Kains B, Desmedt C, Piette F, et al. Comparison of prognostic gene expression signatures for breast cancer. BMC Genomics 2008; 9:394.

Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol 2007; 25(33):5287-312.

Harris LN, Ismaila N, McShane, LM, et al. Use of Biomarkers to guide decisions of adjuvant systemic therapy for women with early stage invasive breast cancer: American Society of Oncology Clinical Practice Guideline. J Clin Oncol. 2016 Feb(34).

Hassett MJ, Silver SM, Hughes ME, et al. Adoption of gene expression profile testing and association with use of chemotherapy among women with breast cancer. J Clin Oncol 2012; 30(18):2218-26.

Hefti MM, Hu R, Knoblauch NW et al. Estrogen receptor negative/progesterone receptor positive breast cancer is not a reproducible subtype. Breast Cancer Res 2013; 15(4):R68.

Henry LR, Stojadinovic A, Swain SM, et al. The influence of a gene expression profile on breast cancer decisions. J Surg Oncol 2009; 99(6):319-23.

Hornberger J, Alvarado MD, Rebecca C, et al. Clinical validity/utility, change in practice patterns, and economic implications of risk stratifiers to predict outcomes for early-stage breast cancer: a systematic review. J Natl Cancer Inst 2012; 104(14):1068-79.

Jankowitz RC, Cooper K, Erlander MG, et al. Prognostic utility of the breast cancer index and comparison to Adjuvant! Online in a clinical case series of early breast cancer. Breast Cancer Res 2011; 13(5):R98.

Jansen MP, Sieuwerts AM, Look MP, et al. HOXB13-to-IL17BR expression ratio is related with tumor aggressiveness and response to tamoxifen of recurrent breast cancer: a retrospective study. J Clin Oncol 2007; 25(6):662-8.

Jerevall PL, Brommesson S, Strand C, et al. Exploring the two-gene ratio in breast cancer-- independent roles for HOXB13 and IL17BR in prediction of clinical outcome. Breast Cancer Res Treat 2008; 107(2):225-34.

Jerevall PL, Ma XJ, Li H, et al. Prognostic utility of HOXB13:IL17BR and molecular grade index in early-stage breast cancer patients from the Stockholm trial. Br J Cancer 2011; 104(11):1762-9.

Joh JE, Esposito NN, Kiluk JV, et al. The effect of Oncotype DX recurrence score on treatment recommendations for patients with estrogen receptor-positive early stage breast cancer and correlation with estimation of recurrence risk by breast cancer specialists. Oncologist 2011; 16(11):1520-6.

Kelly CM, Bernard PS, Krishnamurthy S, et al. Agreement in Risk Prediction Between the 21-Gene Recurrence Score Assay (Oncotype DX(R)) and the PAM50 Breast Cancer Intrinsic Classifier in Early-Stage Estrogen Receptor-Positive Breast Cancer. Oncologist 2012; 17(4):492-8.

Kelly CM, Krishnamurthy S, Bianchini G, et al. Utility of oncotype DX risk estimates in clinically intermediate risk hormone receptor-positive, HER2-normal, grade II, lymph node-negative breast cancers. Cancer 2010; 116(22):5161-7.

Klang SH, Hammerman A, Liebermann N, et al. Economic implications of 21-gene breast cancer risk assay from the perspective of an Israeli-managed health-care organization. Value Health 2010; 13(4):381-7.

Knauer M, Cardoso F, Wesseling J, et al. Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature. Br J Cancer 2010; 103(12):1788-93.

Knauer M, Mook S, Rutgers EJ, et al. The predictive value of the 70-gene signature for adjuvant chemotherapy in early breast cancer. Breast Cancer Res Treat 2010; 120(3):655-61.

Krijgsman O, Roepman P, Zwart W, et al. A diagnostic gene profile for molecular subtyping of breast cancer associated with treatment response. Breast Cancer Res Treat 2012; 133(1):37-47.

Kunz G. Use of a genomic test (MammaPrint) in daily clinical practice to assist in risk stratification of young breast cancer patients. Arch Gynecol Obstet 2011; 283(3):597-602.

Lo SS, Mumby PB, Norton J, et al. Prospective multicenter study of the impact of the 21-gene recurrence score assay on medical oncologist and patient adjuvant breast cancer treatment selection. J Clin Oncol 2010; 28(10):1671-6.

Mamounas EP, Tang G, Fisher B, et al. Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol 2010; 28(10):1677-83.2.04.36.

Martin M, Brase JC, Calvo L, et al. Clinical validation of the EndoPredict test in node-positive chemotherapy-treated ER+/HER2- breast cancer patients: results from the GEICAM/9906 trial. Breast Cancer Res 2014; 16(2):R38.

Ma XJ, Hilsenbeck SG, Wang W, et al. The HOXB13:IL17BR expression index is a prognostic factor in early-stage breast cancer. J Clin Oncol 2006; 24(28):4611-9.

Ma XJ, Salunga R, Dahiya S, et al. A five-gene molecular grade index and HOXB13:IL17BR are complementary prognostic factors in early stage breast cancer. Clin Cancer Res 2008; 14(9):2601-8.

Mook S, Knauer M, Bueno-de-Mesquita JM, et al. Metastatic potential of T1 breast cancer can be predicted by the 70-gene MammaPrint signature. Ann Surg Oncol 2010; 17(5):1406-13.

Mook S, Schmidt MK, Viale G, et al. The 70-gene prognosis-signature predicts disease outcome in breast cancer patients with 1-3 positive lymph nodes in an independent validation study. Breast Cancer Res Treat 2009; 116(2):295-302.

Mook S, Schmidt MK, Weigelt B, et al. The 70-gene prognosis signature predicts early metastasis in breast cancer patients between 55 and 70 years of age. Ann Oncol 2010; 21(4):717-22.

National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: breast cancer, version 3.2014. Available online at: http://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed December 2014.

National Comprehensive Cancer Network (NCCN). Breast cancer. NCCN Clinical Practice Guidelines in Oncology, version 2.2015. Fort Washington, PA: NCCN; 2015.

Nguyen B, Cusumano PG, Deck K, et al. Comparison of molecular subtyping with BluePrint, MammaPrint, and TargetPrint to local clinical subtyping in breast cancer patients. Ann Surg Oncol 2012; 19(10):3257-63.

Nielsen TO, Parker JS, Leung S, et al. A comparison of PAM50 intrinsic subtyping with immunohistochemistry and clinical prognostic factors in tamoxifen-treated estrogen receptor-positive breast cancer. Clin Cancer Res 2010; 16(21):5222-32.

Nielsen T, Wallden B, Schaper C, et al. Analytical validation of the PAM50-based Prosigna BreastCancer Prognostic Gene Signature Assay and nCounter Analysis System using formalin-fixed paraffin-embedded breast tumor specimens. BMC Cancer 2014; 14:177.

Oratz R, Kim B, Chao C, et al. Physician Survey of the Effect of the 21-Gene Recurrence Score Assay Results on Treatment Recommendations for Patients With Lymph Node–Positive, Estrogen Receptor–Positive Breast Cancer. J Oncol Pract 2011; 7(2):94-9.

Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node negative breast cancer. N Engl J Med 2004; 351(27):2817-26.

Paik S, Shak S, Tang G, et al. Risk classification of breast cancer patients by the Recurrence Score assay: comparison to guidelines based on patient age, tumor size, and tumor grade. [Meeting Abstract]. Breast Cancer Res Treat 2004; 88(suppl 1):A104.

Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node negative, estrogen receptor-positive breast cancer. J Clin Oncol 2006; 24(23):3726-34.

Parker JS, Mullins M, Cheang MC, et al. Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 2009; 27(8):1160-7.

Prat A, Parker JS, Fan C, et al. Concordance among gene expression-based predictors for ERpositive breast cancer treated with adjuvant tamoxifen. Ann Oncol 2012.

Reid JF, Lusa L, De Cecco L, et al. Limits of predictive models using microarray data for breast cancer clinical treatment outcome. J Natl Cancer Inst 2005; 97(12):927-30.

Retel VP, Joore MA, Knauer M, et al. Cost-effectiveness of the 70-gene signature versus St. Gallen guidelines and Adjuvant Online for early breast cancer. Eur J Cancer 2010; 46(8):1382-91.

Ring BZ, Seitz RS, Beck R, et al. Novel prognostic immunohistochemical biomarker panel for estrogen receptor-positive breast cancer. J Clin Oncol 2006; 24(19):3039-47.

Ross DT, Kim CY, Tang G, et al. Chemosensitivity and stratification by a five monoclonal antibody immunohistochemistry test in the NSABP B14 and B20 trials. Clin Cancer Res 2008; 14(20):6602-9.

Rutgers E, Piccart-Gebhart MJ, Bogaerts J, et al. The EORTC 10041/BIG 03-04 MINDACT trial is feasible: results of the pilot phase. Eur J Cancer 2011; 47(18):2742-9.

Saghatchian M, Mook S, Pruneri G, et al. Additional prognostic value of the 70-gene signature (MammaPrint) among breast cancer patients with 4-9 positive lymph nodes. Breast 2013; 22(5):682-90.

Sapino A, Roepman P, Linn SC, et al. MammaPrint molecular diagnostics on formalin-fixed, paraffin embedded tissue. J Mol Diagn 2014; 16(2):190-7.

Sestak I, Dowsett M, Zabaglo L, et al. Factors predicting late recurrence for estrogen receptor-positive breast cancer. J Natl Cancer Inst 2013; 105(19):1504-11.

Sgroi DC, Sestak I, Cuzick J, et al. Prediction of late distant recurrence in patients with oestrogenreceptor-positive breast cancer: a prospective comparison of the breast-cancer index (BCI) assay, 21-gene recurrence score, and IHC4 in the TransATAC study population. Lancet Oncol 2013; 14(11):1067-76.

Solin LJ, Gray R, Baehner FL, et al. A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. J Natl Cancer Inst 2013; 105(10):701-10.

Sparano JA, Solin LJ. Defining the clinical utility of gene expression assays in breast cancer: the intersection of science and art in clinical decision making. J Clin Oncol 2010; 28(10):1625-7.

Tang G, Shak S, Paik S, et al. Comparison of the prognostic and predictive utilities of the 21-gene Recurrence Score assay and Adjuvant! for women with node-negative, ER-positive breast cancer: results from NSABP B-14 and NSABP B-20. Breast Cancer Res Treat 2011; 127(1):133-42.

Tutt A, Wang A, Rowland C, et al. Risk estimation of distant metastasis in node-negative, estrogen receptor-positive breast cancer patients using an RT-PCR based prognostic expression signature. BMC Cancer 2008; 8:339.

Tzeng JP, Mayer D, Richman AR, et al. Women's experiences with genomic testing for breast cancer recurrence risk. Cancer 2010; 116(8):1992-2000.

van de Vijver MJ, He YD, van't Veer LJ, et al. A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 2002; 347(25):1999-2009.

Van Laar RK. Design and multiseries validation of a web-based gene expression assay for predicting breast cancer recurrence and patient survival. J Mol Diagn 2011; 13(3):297-304.

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Coding

Inclusion of a code in this table does not imply reimbursement. Eligibility, benefits, limitations, exclusions, precertification/referral requirements, provider contracts, and Company policies apply.

The codes listed below are updated on a regular basis, in accordance with nationally accepted coding guidelines. Therefore, this policy applies to any and all future applicable coding changes, revisions, or updates.

In order to ensure optimal reimbursement, all health care services, devices, and pharmaceuticals should be reported using the billing codes and modifiers that most accurately represent the services rendered, unless otherwise directed by the Company.

The Coding Table lists any CPT, ICD-9, ICD-10, and HCPCS billing codes related only to the specific policy in which they appear.

CPT Procedure Code Number(s)

MEDICALLY NECESSARY

THE FOLLOWING CODE IS USED TO REPRESENT ONCOTYPE DX® BREAST (21-GENE RECURRENCE SCORE)
81519, 81520, 81521, 81518

THE FOLLOWING CODE IS USED TO REPRESENT MAMMAPRINT® (70-GENE SIGNATURE)
81479

THE FOLLOWING CODE IS USED TO REPRESENT PROSIGNA™ / PAM50 BREAST CANCER INTRINSIC SUBTYPE CLASSIFIER
0008M

THE FOLLOWING CODE IS USED TO REPRESENT GENETIC COUNSELING BEFORE AND AFTER GENETIC TESTING
96040


EXPERIMENTAL/INVESTIGATIONAL

THE FOLLOWING CODE IS USED TO REPRESENT BREAST CANCER INDEXSM, MAMMOSTRAT® BREAST CANCER TEST, BREASTONCPX™, NEXCOURSE® BREAST IHC4, BREASTPRS™, ENDOPREDICT™, BLUEPRINT®, AND TARGETPRINT®
81479


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD - 10 Procedure Code Number(s)

N/A


Professional and outpatient claims with a date of service on or before September 30, 2015, must be billed using ICD-9 codes. Professional and outpatient claims with a date of service on or after October 1, 2015, must be billed using ICD-10 codes.

Facility/Institutional inpatient claims with a date of discharge on or before September 30, 2015, must be billed with ICD-9 codes. Facility/Institutional inpatient claims with a date of discharge on or after October 1, 2015, must be billed with ICD-10 codes.


ICD -10 Diagnosis Code Number(s)

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

C50.111 Malignant neoplasm of central portion of right female breast

C50.112 Malignant neoplasm of central portion of left female breast

C50.119 Malignant neoplasm of central portion of unspecified female breast

C50.211 Malignant neoplasm of upper-inner quadrant of right female breast

C50.212 Malignant neoplasm of upper-inner quadrant of left female breast

C50.219 Malignant neoplasm of upper-inner quadrant of unspecified female breast

C50.311 Malignant neoplasm of lower-inner quadrant of right female breast

C50.312 Malignant neoplasm of lower-inner quadrant of left female breast

C50.319 Malignant neoplasm of lower-inner quadrant of unspecified female breast

C50.411 Malignant neoplasm of upper-outer quadrant of right female breast

C50.412 Malignant neoplasm of upper-outer quadrant of left female breast

C50.419 Malignant neoplasm of upper-outer quadrant of unspecified female breast

C50.511 Malignant neoplasm of lower-outer quadrant of right female breast

C50.512 Malignant neoplasm of lower-outer quadrant of left female breast

C50.519 Malignant neoplasm of lower-outer quadrant of unspecified female breast

C50.611 Malignant neoplasm of axillary tail of right female breast

C50.612 Malignant neoplasm of axillary tail of left female breast

C50.619 Malignant neoplasm of axillary tail of unspecified female breast

C50.811 Malignant neoplasm of overlapping sites of right female breast

C50.812 Malignant neoplasm of overlapping sites of left female breast

C50.819 Malignant neoplasm of overlapping sites of unspecified female breast

C50.911 Malignant neoplasm of unspecified site of right female breast

C50.912 Malignant neoplasm of unspecified site of left female breast

C50.919 Malignant neoplasm of unspecified site of 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

C50.121 Malignant neoplasm of central portion of right male breast

C50.122 Malignant neoplasm of central portion of left male breast

C50.129 Malignant neoplasm of central portion of unspecified male breast

C50.221 Malignant neoplasm of upper-inner quadrant of right male breast

C50.222 Malignant neoplasm of upper-inner quadrant of left male breast

C50.229 Malignant neoplasm of upper-inner quadrant of unspecified male breast

C50.321 Malignant neoplasm of lower-inner quadrant of right male breast

C50.322 Malignant neoplasm of lower-inner quadrant of left male breast

C50.329 Malignant neoplasm of lower-inner quadrant of unspecified male breast

C50.421 Malignant neoplasm of upper-outer quadrant of right male breast

C50.422 Malignant neoplasm of upper-outer quadrant of left male breast

C50.429 Malignant neoplasm of upper-outer quadrant of unspecified male breast

C50.521 Malignant neoplasm of lower-outer quadrant of right male breast

C50.522 Malignant neoplasm of lower-outer quadrant of left male breast

C50.529 Malignant neoplasm of lower-outer quadrant of unspecified male breast

C50.621 Malignant neoplasm of axillary tail of right male breast

C50.622 Malignant neoplasm of axillary tail of left male breast

C50.629 Malignant neoplasm of axillary tail of unspecified male breast

C50.821 Malignant neoplasm of overlapping sites of right male breast

C50.822 Malignant neoplasm of overlapping sites of left male breast

C50.829 Malignant neoplasm of overlapping sites of unspecified male breast

C50.921 Malignant neoplasm of unspecified site of right male breast

C50.922 Malignant neoplasm of unspecified site of left male breast

C50.929 Malignant neoplasm of unspecified site of unspecified male breast




HCPCS Level II Code Number(s)



MEDICALLY NECESSARY
THE FOLLOWING CODE IS USED TO REPRSENT MAMMAPRINT®

S3854 Gene expression profiling panel for use in the management of breast cancer treatment

THE FOLLOWING CODE IS USED TO REPRESENT INTERPRETATION AND REPORT

G0452 Molecular pathology procedure; physician interpretation and report

THE FOLLOWING CODE IS USED TO REPRESENT GENETIC COUNSELING BEFORE AND AFTER GENETIC TESTING

S0265 Genetic counseling, under physician supervision, each 15 minutes


EXPERIMENTAL/INVESTIGATIONAL

THE FOLLOWING CODE IS USED TO REPRESENT BREAST CANCER INDEXSM, MAMMOSTRAT® BREAST CANCER TEST, BREASTONCPX™, NEXCOURSE® BREAST IHC4, BREASTPRS™, ENDOPREDICT™, BLUEPRINT®, AND TARGETPRINT®

S3854 Gene expression profiling panel for use in the management of breast cancer treatment



Revenue Code Number(s)

N/A


Misc Code

N/A:

N/A


Coding and Billing Requirements


Cross References


Policy History

Revisions from 06.02.27l:
01/01/2019Effective 01/01/2019, the following procedure code was added to this policy due to coding updates (this procedure code is only medically necessary when medical necessity criteria associated with it are met):

81518

Revisions from 06.02.27k
11/21/2018This policy has been reissued in accordance with the Company's annual review process.
01/01/2018Effective 01/01/2018, the following procedure codes were added to this policy due to coding updates (these procedure are only medically necessary when medical necessity criteria associated with them are met):

81520, 81521


Revisions from 06.02.27j
11/22/2017This policy has been reissued in accordance with the Company's annual review process.


Effective 10/05/2017 this policy has been updated to the new policy template format.


Version Effective Date: 01/01/2019
Version Issued Date: 01/02/2019
Version Reissued Date: N/A

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