Genetic Assays of Tumor Tissue to Predict Prognosis of Breast Cancer*

Medical Policy: 02.04.09 
Original Effective Date: December 2005 
Reviewed: June 2011 
Revised: July 2008 


Benefit Application
Benefit determinations are based on the applicable contract language in effect at the time the services were rendered. Exclusions, limitations or exceptions may apply. Benefits may vary based on contract, and individual member benefits must be verified. Wellmark determines medical necessity only if the benefit exists and no contract exclusions are applicable. This medical policy may not apply to FEP. Benefits are determined by the Federal Employee Program.

This Medical Policy 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 will be reviewed regularly and be updated as scientific and medical literature becomes available.

Description: 

For women with early stage breast cancer, 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-positive, and lymph node-negative. These women have an approximately 15% baseline risk of recurrence; approximately 85% of these patients 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 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 gold standard, and several common criteria have qualitative or subjective components that add variability to risk estimates. As a result, more patients 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 physician.

 

Recently, several groups have identified panels of gene expression markers (“signatures”) that appear to predict the baseline risk of breast cancer recurrence after surgery, radiation therapy, and hormonal therapy (for hormone receptor-positive tumors) in women with node-negative disease.  Five gene expression tests are commercially available in the U.S.: Oncotype DX™ (a 21-gene RT-PCR assay; Genomic Health), the 70-gene signature MammaPrint® (Agendia), Mammostrat® Breast Cancer Test (Clarient Diagnostic Services), the Breast Cancer Index SM, a combination of the Molecular Grade Index (MGI) and the BOXB13:IL17BR Index (bioTheranostics), the BreastOncPx™  (Breast Cancer Prognosis Gene Expression Assay; LabCorp), and the PAM50 Breast Cancer Intrinsic Classifier (ARUP National Reference Laboratory). If these panels are more accurate then current conventional classifiers, they could be used to aid chemotherapy decision-making, where current guidelines do not strongly advocate its use, without negatively affecting disease-free and overall survival outcomes.


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Prior Approval: 

 

Prior approval is recommended. Submit a prior approval now. 


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Policy: 

The use of OncoType DX™ to predict recurrence risk for deciding whether or not to undergo adjuvant chemotherapy may be considered medically necessary in women newly diagnosed with breast cancer meeting all of the following characteristics:

  • Unilateral, non-fixed tumor;
  • Node-negative (lymph nodes with micrometastases not greater than 2 mm are considered negative for purposes of this policy statement)
  • Hormone-receptor-positive (ER-positive or PR-positive)
  • Human epidermal growth factor receptor 2 (HER2)-negative
  • Tumor size 0.6 to 1.0 cm with moderate/poor differentiation or unfavorable features (i.e., angiolymphatic invasion, high histologic grade, or high nuclear grade), OR tumor size > 1 cm
  • who will be treated with  adjuvant endocrine therapy, e.g., tamoxifen or aromatase inhibitors
  • when the result will aid the patient in making the decision regarding chemotherapy (i.e., when chemotherapy is a therapeutic option) AND
  • when ordered within six months following diagnosis, since the value of the test for making decisions regarding delayed chemotherapy is unknown

 

Oncotype DX™ should only be ordered after surgery and subsequent pathology examination of the tumor has been completed. Oncotype DX should not be ordered to determine or confirm ER/PR and HER2 status.

 

For patients who otherwise meet the above characteristics but who have multiple ipsilateral primary tumors, a specimen from the tumor with the most aggressive histological characteristics should be submitted for testing. It is not necessary to conduct testing on each tumor; treatment is based on the most aggressive lesion.

 

All other indications for OncoType DX™ , including determination of recurrence risk in breast cancer patients with positive lymph nodes, are considered investigational.

 

The use of MammaPrint® for any indication is considered investigational because there is insufficient evidence to determine whether it is better than conventional risk assessment tools in predicting recurrence.

 

The use of other gene expression assays (e.g., Mammostrat Breast Cancer Test, the Breast Cancer Index, the BreastOncPx, or the PAM50 Breast cancer Intrinsic Classifier) for any indication is considered investigational because there is insufficient evidence to determine whether any of these assays are better than conventional risk assessment tools in predicting recurrence.

 

Oncotype DX is an assay that measures the expression of 21 genes (16 cancer genes and 5 reference genes) in RNA extracted from samples of tissue from a primary breast tumor. The initial indications provided by Genomic Health were newly diagnosed breast cancer patients with stage I or II disease that is node negative and estrogen receptor (ER) positive, who were treated with tamoxifen. Primary validation studies enrolled node-negative women. More recently, Genomic Health has expanded their indication to include all stage II disease (tumor ≤2 cm with spread to axillary lymph nodes or 2-5 cm without lymph node involvement). Results from the Oncotype DX 21-gene expression profile are combined into a recurrence score (RS). Based on a study of analytic validity, tissue sampling rather than technical performance of the assay is likely to be the greatest source of variability in results. The 21-gene expression profile was validated in studies using archived tumor samples from subsets of patients enrolled in already completed randomized controlled trials of early breast cancer treatment. Patients enrolled in the trial arms from which specimens were obtained had primary, unilateral breast cancer with no history of prior cancer and were treated with tamoxifen; tumors were ER-positive, most were HER2-negative, and in the case of at least 1 trial multifocal tumors were excluded.

 

Several studies have been published regarding the impact of RS results on chemotherapy recommendations by medical oncologists. In general, these studies report that comparing recommendations made prior to and revised after knowledge of RS results show that decisions change in 30-40% of patients, most often from endocrine therapy plus chemotherapy to endocrine therapy alone. Some view these decision changes as evidence of clinical utility because more patients avoid the toxicity of chemotherapy, however there are no patient outcomes attached to these studies; outcomes are assumed based on the original assay clinical validity evidence. In addition, none of the studies formalize and describe the way in which information is delivered to the patient, not do they evaluate how patient preferences are incorporated into the final treatment decision.

 

Limitations of the current evidence, such as confirmation of optimal RS cutoff values for tamoxifen-treated and separately for AI-treated patients and recommendations for patients with intermediate RS values, are expected to be answered by the results of the ongoing Trial Assigning Individualized Options for Treatment (Rx), also known as TAILORx.

 

Based on a study published in May 2008 that compared the Oncotype DX ER and PR results to traditional immunohistochemistry (IHC) results, Genomic Health is now including the quantitative ER and PR component results in the Oncotype DX 21-gene profile report. The study reported 90% or better concordance between the two assays, but that quantitative ER by Oncotype DX was more strongly associated with disease recurrence that the IHC results. However, both ER and PR analysis is traditionally conducted during pathology examination of all breast cancer biopsies, whereas Oncotype DX is indicated only for known ER-positive tumors, after the pathology examination is complete, the patient meets specific criteria, and patient and physician are considering preferences for risk and chemotherapy. Thus, Oncotype DX should not be ordered as a substitute for ER and PR IHC. Additionally, accepted guidelines for ER and PR testing outline standards for high quality IHC testing and do not recommend confirmatory testing; thus the 21-gene RS should not be ordered to confirm ER/PR IHC results. Similarly, guidelines for HER2 testing specify IHC and/or fluorescence in situ hybridization (FISH) methods. Although the HER2 component of the 21-gene assay has been shown to strongly correlate to FISH results, the 21-gene assay should not be ordered to determine or confirm HER2.

 

A study by Albain et al, published in 2010, evaluated samples from the Southwest Oncology Group Trial 8814, in which randomized node-positive, ER-positive patients treated with tamoxifen for 5 years were compared to those treated with cyclophosphamide, doxorubicin, fluorouracil (CAF) chemotherapy followed by tamoxifen (CAF-T) for 5 years. Samples were available for determination of RS for 41% (n=148) and 39% (n=219) of the trial arms, respectively. In this study, 10-year disease-free survival (DFS) and overall survival (OS) outcomes in the tamoxifen study arm differed by RS risk category (p=0.017 and 0.003, respectively), indicating that the RS is prognostic. When the two treatment arms were compared within the RS categories, only patients in the high RS category significantly benefited from the addition of CAF to tamoxifen (for DFS, 42% [tamoxifen] vs. 55% [CAF-T], p=0.033; for OS, 51% [tamoxifen] vs. 68% [CAF-T]. p=0.027) suggesting that RS is also predictive of response to chemotherapy.

 

A multivariate analysis of RS interaction with DFS, adjusted for number of positive nodes, was significant for the first 5 years of follow-up at p=0.029, and remained significant after adjusting for age, race, tumor size, progesterone receptor status, grade, p53, and HER2. However, the interaction was not significant (p=0.15) after adjusting for ER level (ER gene expression is a component of the 21-gene profile). Interaction results were similar for OS.

 

Dowsett et al. included a separate evaluation of node-positive patients in their examination of the ATAC trial samples. Of 306 node-positive patients, 243 had 1-3 involved nodes, and 63 patients 4 or more; these were not evaluated separately. Rates of distant recurrence at 9 years were 17% (95% CI, 12-24%), 28% (20-39%), and 49% (35-64%), respectively. It is not clear that the risk of distant recurrence in low-risk RS patients would be sufficiently low to forgo the choice of chemotherapy. The authors note that their study did not directly evaluate the value if RS in predicting the benefit of chemotherapy. Goldstein et al evaluated samples from the Eastern Cooperative Oncology Group E2197 trial, which included patients with 0-3 positive lymph nodes and operable tumor > 1cm in size. Patients were randomly assigned to doxorubicin plus cyclophosphamide or docetaxel plus 5 years endocrine therapy but outcomes were not significantly different for the study arms.

 

Oratz et al. surveyed oncologists who are already ordering Oncotype DX for lymph node-positive patients to determine the effect of the assay results on treatment recommendations and reported that approximately half changed their recommendations after receiving RS results, with 33% recommending endocrine therapy alone instead of endocrine therapy plus chemotherapy. The majority of the 160 respondents (16% response rate) reported being satisfied with the data supporting the use of the assay on node-positive disease. However, medical oncologists who treat breast cancer patients were not surveyed in general, only those who are already using the assay, thus skewing the results. Finally, no outcomes were reported so the study provided no firm evidence of clinical utility in this population.

 

Additional studies are necessary before it is possible to confidently withhold currently recommended chemotherapy from lymph node-positive breast cancer patients with low/intermediate RS results, The RxPONDER (Rx for Positive Node Endocrine Responsive Breast Cancer) trial, led by the Southwest Oncology Group will enroll 4,000 women with RS ≤25 who have early stage, hormone receptor-positive, HER2-negative breast cancer involving one to three lymph nodes. Patients will be randomized to receive either chemotherapy with endocrine therapy or endocrine therapy alone.

 

MammaPrint is a 70-gene signature prognostic test for women younger than 61 years with ER-positive or ER-negative, lymph node-negative breast cancer. A 2008 Blue Cross Blue Shield Association Technology Evaluation Center (TEC) Assessment found insufficient evidence to determine whether MammaPrint is better than conventional risk assessment tools in predicting recurrence. Limited technical performance evaluation of the commercial version of the assay suggests good reproducibility. Recurrence rates of patients classified as low risk in available studies were 15-25%, likely too high for most patients and physicians to consider foregoing chemotherapy.

 

In a study published in 2009, Mook et al. studied 241 patients with 1-3 positive lymph nodes and primarily ER-positive, HER2-negative tumors treated variably. The 70-gene signature was a significant predictor of outcome and reclassification analysis using Adjuvant! Online vs. MammaPrint. Results showed significant additional discrimination by the gene signature, but all were confounded by heterogeneous patient treatment. This study also updated the results of 106 patients with 1-3 positive lymph nodes from the validation study reporting 98% (95% CI, 94-100%) 10-year breast cabcer-specific survival for good prognosis signatures vs. 64% (52-76%) for poor prognosis signatures; adjusted HR 3.63 (0.88-14.96), p=0.07. Based on these results, the ongoing MINDACT trial of MammaPrint was enlarged to include patients with 1-3 positive lymph nodes.

 

Studies published in 2010 and 2011 comprise primarily small case series, and pooled re-analyses of subgroups from previously reported retrospective studies. None of the published results provide sufficient evidence to alter the current policy position. The studies of the 70-gene signature suffer from confounding in heterogeneous sample populations. Pooled re-analyses of subpopulations may control for one variable, but confounding remains for other variables. Results for the good prognosis patients have confidence intervals that extend into ranges that likely confer risk that is too great for patients and providers to bear.

 

The Breast Cancer Index is a simultaneous assessment of HOXB13:IL17BR Index and the MGISM (Molecular Grade Index). A 2008 Blue Cross Blue Shield Association TEC Assessment reviewed available studies for the original component assays. There was insufficient evidence to determine whether the H/I ratio is better than conventional risk assessment tools in predicting recurrence. Ten-year recurrence rates of patients classified as low risk in available studies were 17-25%, likely too high for most patients and physicians to consider foregoing chemotherapy. The MGI is intended to measure tumor grade using the expression of 5 cell cycle genes, and to provide prognostic information in ER-positive patients regardless of nodal status.

 

Mammastrat Breast Cancer Test is an IHC test intended to evaluate risk of breast cancer recurrence in postmenopausal, node-negative, ER-positive breast cancer patients who will receive endocrine therapy and are considering adjuvant chemotherapy. The test employs 5 monoclonal antibodies to detect gene expression of proteins biologically independent of each other and not involved in cell proliferation, hormone receptor status, or growth/differentiation, thus potentially allowing integration with clinically routine biomarkers. A proprietary diagnostic algorithm is used to calculate a risk score and to classify patients into high-, moderate-, or low-risk categories.

 

One published study described the development of the assay but provided no information on analytic validity. In a validation study in an independent cohort, a multivariable model predicted 50%, 70%, and 87% 5-year disease-free survival for patients classified as high, moderate, and low prognostic risk, respectively, by the test results (p=0.0008). An additional study of the same trail samples used for Oncotype DX validation (NSABP B-14 and B-20 trials) found that among patients with early, node-negative breast cancer treated only with tamoxifen, those stratified by Mammostrat into low, moderate, and high-risk groups had recurrence-free survival estimates of 85%, 85%, and 73%, respectively.  Both low- and high-risk groups benefitted significantly from chemotherapy treatment, but high-risk patients benefitted to a greater degree. The moderate-risk group was not well-separated from the low-risk group and thus, moderate-risk results do not appear to provide clinically useful information.

 

The BreastOncPx test is an RT-PCR test performed on formalin-fixed, paraffin-embedded tissue that measures the gene expression of 14 genes associated with key functions such as cell cycle control, apoptosis, and DNA recombination and repair. The results are combined into a metastasis score, which is reported to be associated with the risk of distant metastases in patients who are node-negative and estrogen-receptor positive. Information on the development and validation of the test has been published, but no information on analytic validity is provided. The validation study includes a ROC analysis comparing the test with Adjuvant!, but there is no clear evidence supporting clinical utility.

 

The PAM50 Breast Cancer Intrinsic Classifier is a qRT-PCR test based on a panel of 50 genes to identify the breast cancer “intrinsic” subtypes luminal A, luminal B, HER2-enriched, and basal-like, and to generate risk-of-relapse scores in node-negative patients who had not had systemic treatment for their cancer. In 2010, a study was published comparing the PAM50 classifier with standard clinicopathologic factors as represented by Adjuvant! Online and with models based on immunohistochemistry for biomarkers of intrinsic subtypes. The study used samples from patients diagnosed between 1986 and 1992 with ER-positive breast cancer, either higher-risk (i.e. lymphovascular invasion) node-negative or node-positive disease and treated with five years of tamoxifen but no adjuvant chemotherapy. In the node-negative population, Adjuvant! Online was inferior to all other biomarker models for predicting recurrence and disease-specific survival. A model including the PAM50 risk of recurrence gene expression signature that also incorporated the influence of proliferation and tumor size identified patients with a greater than 95% chance of remaining alive and disease-free beyond 10 years. A slightly different gene expression model best fir the node-positive population, but did not identify a sufficiently low-risk population that adjuvant hormone therapy would likely be considered sufficient. Because the cohort used to generate the models evaluated in this study was biased toward higher-risk early breast cancers, it is likely not generalizable. Nor did the authors clearly identify a final model for clinical use. Rather, the authors outlined potential additional studies.



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Procedure Codes and Billing Guidelines: 

  • To report provider services, use appropriate CPT* codes, Modifiers, Alpha Numeric (HCPCS) level 2) codes, Revenue codes, and/or ICD-9-CM diagnostic codes.
  • HCPCS S3854 Gene expression profiling panel for use in the management of breast cancer treatment 

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Selected References: 

  • Esteva FJ, Sahin AA, Cristofanilli M et al. Prognostic role of a multigene reverse transcriptase-PCR assay in patients with Node-negative breast cancer not receiving adjuvant systemic therapy. Clin Cancer Res. 2005; 11(9):3315-3319.
  • 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):2817-2826.
  • Wang Y, Klijn JGM, Zhang Y et al. Gene-expression profiles to predict distant metastasis of lymph-node-negative primary breast cancer. Lancet 2005; 365:671-79.
  • Gianni L, Zambetti M, Clark K et al. Gene expression profiles of paraffin-embedded core biopsy tissue predict response to chemotherapy in patients with locally advanced breast cancer. J Clin Oncol. 2004; 22 (14 Suppl):501 [Abstract].
  • Hannemann J, Oosterkanp HM, Bosch CA et al. Changes in gene expression profiling due to primary chemotherapy in patients with locally advanced breast cancer. J Clin Oncol. 2004; 22(14 Suppl):502 [Abstract].
  • Van de Vijver MJ, He YD, Van 't Veer LJ et al. A gene-expression signature as a predicator of survival in breast cancer. N Engl J Med. 2002; 347(25):1999-2009.
  • Habel LA, Quesenberry CP, Jacobs M et al. Gene expression and breast cancer mortality in Northern California Kaiser Permanente patients; a large population-based case control study. Proceedings from the 41st Annual Meeting of the American Society of Clinical Oncology. May 13-17, 2005. Orlando, FL. Abstract #603.
  • ECRI. Oncotype DXTM Assay to Predict Recurrence in Breast Cancer. Plymouth Meeting (PA): ECRI Health Technology Information Service; 2005. (ECRI Hotline Response).
  • Blue Cross Blue Shield Association Technology Evaluation Center. Gene Expression Profiling for Managing Breast Cancer Treatment. Assessment Program 2005; 20(3).
  • Hayes Inc. Gene Expression Profiling of Tumor Tissue to Predict Breast Cancer Recurrence. Hayes Alert. September 2005; VIII(9).
  • 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 Aug 10;24(23):3717-8.
  • TARGET [database online]. Plymouth Meeting (PA): ECRI; 2006 Aug. Gene expression assay for predicting recurrence of breast cancer.
  • Goldhirsch A, Wood W, Gelber R et al.Progress and promise: highlights of the international expert consensus on the primary therapy of early breast cancer 2007. Ann Oncol 2007;18(7):1133-44.
  • Mina L, Soule SE, Badve S et al. Predicting response to primary chemotherapy: gene expression profiling of paraffin-embedded core biopsy tissue. Breast Caner Res treat 2007;103(2):197-208.
  • 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.
  • 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.
  • 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 Nov 20;25(33). Published ahead of print on October 22, 2007 as 10.1200/JCO.2007.14.2364.
  • Emerging Technology (TARGET) Evidence Report. Plymouth Meeting (PA): ECRI Institute; January 2008. Gene expression profiling of breast cancer to predict the likelihood of recurrence.
  • Ma X-J, 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):2601-2608.
  • Jerevall PL, Brommesson S, Strand C et al. Exploring the two-gene ration in breast cancer-independent roles for HOXB13 and IL17BR in prediction of clinical outcome.  Breast Cancer Res Treat. 2008 Jan;107(2):225-34. E-pub 2007 Apr 24.
  • 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 Feb 20;25(6):662-8.
  • National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines on Oncology: Breast Cancer. v.1.2010. Available online at www.nccn.org/professionals/physician_gls/PDF/breast.pdf. Last accessed February 2010.
  • Bueno-de-Mesquita JM, Linn SC, Keijzer R et al. Validation of 70-gene prognosis signature in node-negative breast cancer. Breast Cancer Res Treat 2009; 117(3):483-95.
  • 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.
  • 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.
  • 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 anastrazole or tamoxifen: a TransATAC study. J Clin Oncol 2010; 28(11):1829-34.
  • 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.
  • 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 B14 and NSABP B-20. J Clin Oncol 2010; 28(10):1677-83.
  • 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.
  • Ademuyiwa FO, Miller A, O’Connor T et al. The effects of Oncotype DX recurrence scores on chemotherapy utilization in a multi-institutional breast cancer cohort. Breast Cancer Res Treat 2011; 126(3):797-802.
  • 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.
  • Albain KS, Barlow WE, Shak S et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lanet Oncol 2010; 11(1):55-65.
  • 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. Journal of Oncology Practice 2011; 7(2):94-9.
  • 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.
  • Kunz G. Use of 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.
  • Bighin C, Del Mastro L, Canavese G et al. Use in current clinical practice of 70-gene signature in early breast cancer. Int J Cancer 2010; 21(4):717-22.
  • Mook S, Schmidt MK, Weigelt B et al. The 70-gene prognosis signature versus St. Gallen guideliens and Adjuvant! Online for early breast cancer. Eur J Cancer 2010; 46(8):1382-91.
  • 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.

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Policy History: 

 

 

Date                                        Reason                               Action

June 2011                               Annual review                    Policy renewed


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Wellmark medical policies address the complex issue of technology assessment of new and emerging treatments, devices, drugs, etc.   They are developed to assist in administering plan benefits and constitute neither offers of coverage nor medical advice. Wellmark medical policies contain only a partial, general description of plan or program benefits and do not constitute a contract. Wellmark does not provide health care services and, therefore, cannot guarantee any results or outcomes. Participating providers are independent contractors in private practice and are neither employees nor agents of Wellmark or its affiliates. Treating providers are solely responsible for medical advice and treatment of members. Our medical policies may be updated and therefore are subject to change without notice.

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