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TEC Assessment Index

Gene Expression Profiling of Breast Cancer to Select Women for Adjuvant Chemotherapy

Assessment Program
Volume 22, No. 13
November 2007

Executive Summary

Background

For women with early stage breast cancer, adjuvant chemotherapy provides a significant proportional benefit, i.e., benefit that is the same regardless of prognosis, and regardless of hormonal treatment for hormone-receptor-positive tumors. However, in all cases, the absolute benefit of chemotherapy depends on the baseline risk of recurrence. For example, women with the best prognosis have small tumors that are estrogen-receptor (ER) positive, and disease that is lymph-node negative. After tamoxifen therapy, these women have an approximately 15% baseline risk of recurrence. On average, this population also receives a small, but significant, absolute benefit from chemotherapy. However, approximately 85% of these patients would be disease free at 10 years with tamoxifen treatment alone. Current risk classifiers do not accurately identify those early stage patients who are at low risk of recurrence; as a result, more patients are treated with chemotherapy than can benefit. Better predictors of baseline risk could help women who prefer to avoid the toxicity of chemotherapy, if assured that their risk is low, make better treatment decisions in consultation with their physicians.

Conventional risk classifiers include the National Comprehensive Cancer Network guidelines, St. Gallen consensus recommendations, and Adjuvant! Online. These classifiers estimate recurrence risk by considering criteria such as tumor size, type, grade, and histologic characteristics; hormone receptor status; and lymph node status. Clinical trial data and physician experience support the development and regular updates of these classifiers, and studies show significant predictive ability. However, no single classifier is considered a gold standard, and several common criteria have qualitative or subjective components that add variability to risk estimates. Moreover, differences among criteria or their use in different classifiers may result in significantly different risk estimates for the same patients. Thus, quantitative risk predictors with greater accuracy are needed.

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 ER-positive tumors) in women with node-negative disease. If these panels are more accurate than current conventional classifiers, they could be used to aid chemotherapy decision-making, in cases where current guidelines only advise considering chemotherapy without strong recommendations either way, without negatively affecting disease-free and overall survival outcomes.

Three gene expression tests for evaluating recurrence risk in early stage breast cancer are commercially available in the U.S. at the time of this writing. Genomic Health, Inc. (Redwood City, CA) developed and markets Oncotype DX™. AviaraDx, Inc. (Carlsbad, CA) licensed the Breast Cancer Gene Expression Ratio to Quest Diagnostics (test also known as the 2-gene ratio or HOXB13/IL-17BR ratio) and also offers the test at its in-house laboratory facility. MammaPrint® was commercially developed by Agendia (the Netherlands; test originally referred to as the 70-gene signature) and is the only test that is cleared by the U.S. Food and Drug Administration (FDA). However, MammaPrint® is performed only in the Agendia Netherlands laboratory, and U.S. samples must be sent there using a sample collection kit provided by the laboratory. This Assessment will focus on all three tests. Other multigene test panels are in various stages of development and will not be evaluated here.

Objective

This Assessment examines whether, compared to conventional risk assessment tools, the use of gene expression profiling improves outcomes when used to decide whether risk of recurrence is low enough to forego adjuvant chemotherapy for early stage breast cancer.

Search Strategy

For this update, MEDLINE® was searched (via PubMed) for “Breast Neoplasms”[MeSH®] AND (“Gene Expression Profiling”[MeSH®] OR “Gene Expression”[MeSH]®) from January 2005 through December 2007.

Selection Criteria

Included studies were full-length journal publications reporting on the use of gene expression panels to predict breast cancer recurrence for the purpose of identifying women with early stage breast cancer who were likely to benefit from postoperative adjuvant chemotherapy. Unpublished studies that analyzed data from published studies, where the full presentation was available, were also accepted as evidence.

We included studies reporting evidence of statistical association between gene expression profiling results and patient outcomes (disease recurrence), which comprised the majority of the evidence. However, while associational evidence is a necessary first step and is useful for making predictions regarding populations, it is not sufficient evidence of improved risk prediction for individual patients. Therefore, in the absence of prospective clinical trials of clinical utility, we also searched for studies reporting either reclassification studies (individual patient risk first classified by conventional clinical criteria, then reclassified by gene expression profile result), or receiver operating curve (ROC) analysis.

Main Results

Oncotype DX.™ The Oncotype DX™ gene expression profile was validated in studies that used archived tumor samples (obtained at surgery) where available from subsets of patients enrolled in already completed, randomized, controlled trials of treatment for ER-positive, node-negative breast cancer. Results from the Oncotype DX™ gene panel are combined into a recurrence score (RS). Retrospective epidemiologic analyses of these samples indicate strong, independent associations between Oncotype DX™ RS results and distant disease recurrence or death from breast cancer (Table; Paik et al. 2004a; Habel et al. 2006). In additional studies using the data from Paik 2004a (Paik et al. 2004b; Bryant 2005), patient risk levels were individually classified by conventional risk classifiers, then reclassified by Oncotype DX™.

Table. Summary of Oncotype Dx™ RS and recurrence risk studies.
Study
Study Type		 Total N Study Objective Results
Paik et al. 2004a

TAM arm of NSABP B-14 RCT		 668 Predict recurrence
RS Risk % of patients K-M Distant recurrence at 10 yr, % (95% CI)
Low 51 6.8 (4.0-9.6)
Int 22 14.3 (8.3-20.3)
High 27 30.5 (23.6-37.4)
All 100 15 (12.5-17.9)
Paik et al. 2004b

Additional analysis of Paik et al. 2004a data 		668 Reclassification study; determine incremental risk compared to conventional classifier
Risk Classification by NCCN1 Risk Reclassification by Oncotype DX N % DRF at 10 yr (95% CI2)
Low (8%) Low 38 100 (NR)
Int 12 80 (59-100)
High 3 56 (13-100)
High (92%) Low 301 93 (89-96)
Int 137 86 (80-92)
High 178 70 (62-77)
Bryant 2005

Additional analysis of Paik et al. 2004a data 		668 Reclassification study; determine incremental risk compared to conventional classifier
Risk Classification by Adjuvant! Online1 Risk Reclassification by Oncotype DX N % recurrence at 10 yr (95% CI2)
Low (53%) Low 216 5.6 (2.5-9)
Int-High 138 12.9 (7-19)
Int-High Low 122 8.9 (4-14)
Int-High 192 30.7 (24-38)
Habel et al. 2006

Case-control 		255 ER+ TAM+; 361 ER+ TAM- Predict mortality
RS Risk 10-yr Absolute Risk of Death, % (95% CI)
ER+, TAM-treated 		10-yr Absolute Risk of Death, % (95% CI)
ER+, No TAM
Low (<18) 2.8 (1.7-3.9) 6.2 (4.5-7.9)
Int (18-30) 10.7 (6.3-14.9) 17.8 (11.8-23.3)
High (>e;30) 15.5 (7.6-22.8) 19.9 (14.2-25.2)

Abbreviations: DRF: distant recurrence free; ER: estrogen receptor; int: intermediate; K-M: Kaplan Meier; N: total number of patients; NCCN: National Comprehensive Cancer Network; NR: not reported; RS: Oncotype DX™ recurrence score; NSABP, National Surgical Adjuvant Breast and Bowel Project; RCT: randomized controlled trial; TAM: tamoxifen;
1 Percentages are percent of total N.
2 Estimated from graphs. Note that different outcomes were reported between Paik et al. 2004b and Bryant 2005 and could not be converted to similar outcomes with confidence intervals.

Bryant J. (2005). Toward a more rational selection of tailored adjuvant therapy data from the National Surgical Adjuvant Breast and Bowel Project. 2005 St. Gallen Breast Cancer Symposium. [Complete slide presentation via Genomic Health]
Habel LA, Quesenberry CP, Jacobs MK et al. (2006). A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients. Breast Cancer Res, 8(3):R25. Epub 2006 May 31.
Paik S, Shak S, Tang G et al. (2004a). A multi-gene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med, 351:2817-26.
Paik S, Shak S, Tang G et al. (2004b). Risk classification of breast cancer patients by the Recurrence Score assay: comparison to guidelines based on patient age, tumor size, and tumor grade. Breast Cancer Res Treat, 88(Suppl 1):A104 [Abstract].

Results indicate that Oncotype DX™ adds additional risk information to the conventional clinical classification of individual high-risk patients, and identifies a subset of patients who would otherwise be recommended for chemotherapy, but are actually at lower risk of recurrence (average 7–9% risk at 10 years; upper 95% confidence interval [CI] limits, 11–14%). Oncotype DX™ testing also identifies a subset of conventionally classified low-risk patients who are reclassified at higher risk of recurrence. However, due to wide confidence intervals, it is not clear that all reclassified higher-risk individuals would realize a net benefit from chemotherapy.

A community-based study of women with ER-positive tumors provides supportive evidence of clinical validity with results of a strong association between RS results and risk of death from breast cancer. Finally, a study in which samples from a randomized, controlled trial of ER-positive, node-negative breast cancer patients treated with tamoxifen versus tamoxifen plus chemotherapy were tested by Oncotype DX™ showed that RS high-risk patients derived clear benefit from chemotherapy, whereas, the average benefit for other patients was not statistically significant, although the confidence intervals were wide and included the possibility of a small benefit.

MammaPrint®. Validation studies of the MammaPrint® gene signature were conducted using banked samples from consecutive series or other convenience samples, rather than samples from randomized, controlled clinical trials. Patients and tumor samples had variable clinical characteristics, making it difficult to characterize the patients who may benefit from this test. Adjusted hazard ratios for distant metastases suggest that the test provides recurrence risk information in addition to conventional classification criteria; the strongest associations appear in the first 5 years of follow-up. Average 10-year disease-free recurrence in low-risk patients by MammaPrint® was approximately 85–88% in two studies, with a lower confidence limit of 74–79%. However, ROC analysis in an independent multicenter validation study suggests only slightly improved predictive accuracy for time to distant metastases with MammaPrint® compared to other conventional criteria. In one study, after Adjuvant! Online risk classification, patients reclassified as low risk by the 70-gene signature in either Adjuvant! Online risk group had 10-year disease-free survival rates of 88–89%, with lower confidence limits of 74–77%. Patients reclassified as high risk had 10-year disease-free survival rates of 69%, with lower confidence limits of 45–61% and upper confidence limits of 76–84%.

Breast Cancer Gene Expression Ratio. The Breast Cancer Gene Expression ratio was significantly and independently associated with poorer disease-free survival in two studies of lymph-node-negative, ER-positive, tamoxifen-treated patients with breast cancer. Patients who were low risk by the 2-gene expression ratio had average 10-year recurrence rates of about 17–25%. Two additional studies in heterogeneous populations of patients also support a statistical association between the 2-gene expression ratio and recurrence-free survival. No ROC or reclassification analyses show whether the Breast Cancer Gene Expression Ratio better classifies conventionally classified high-risk patients according to recurrence outcomes.

Author's Conclusions and Comments

Oncotype DX.™ Epidemiologic analyses show that Oncotype DX™ RS is strongly and independently associated with the risk of distant recurrence or death from breast cancer in patients with lymph-node-negative, estrogen-receptor positive breast cancer who were treated with tamoxifen and who met other specific trial enrollment criteria. Additionally, Oncotype DX™ provides information about the risk of recurrence that is incremental to conventional classifiers used to predict risk. Women classified as high risk by conventional methods and reclassified as low risk by Oncotype DX™ have a recurrence of at most 10–14% and likely less at lower RS values in the low-risk spectrum.

Chemotherapy provides the same proportional benefit to all patients, but the absolute benefit will be very low when the prior risk is low; such a low absolute benefit may not be perceived by patient and physician as outweighing the harms of chemotherapy. 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. The lower the RS value, the greater the confidence the woman can have that chemotherapy will not provide net benefit; outcomes are improved by avoiding chemotherapy toxicity.

Recently, several organizations have updated their guidelines for recommended therapy at different levels of risk determined by Oncotype DX™:

  • The American Society of Clinical Oncology (ASCO) “2007 Update of Recommendations for the Use of Tumor Markers in Breast Cancer” indicates that the Oncotype DX™ assay can be used to predict the risk of recurrence in newly diagnosed patients with node-negative, estrogen-receptor positive breast cancer, who will be treated with tamoxifen; and to identify patients who may not require adjuvant chemotherapy. The recommendations state, “Although performed retrospectively, the validation of this assay using a prospectively collected clinical trial data set, but retrospectively collected tissues from the data set, might be considered as Level of Evidence I [best] for use of this assay.”
  • The National Comprehensive Cancer Network (NCCN) Breast Cancer Clinical Practice Guidelines (2008) indicate that the “21-gene RT-PCR assay” (Oncotype DX™) can be considered for patients with hormone receptor-positive, HER2-negative disease and tumor greater than 1 cm in size, or 0.6–1 cm and moderately/poorly differentiated or with unfavorable features, prior to making decisions about optional chemotherapy. The recommendation is categorized as “nonuniform NCCN consensus (but no major disagreement), based on lower level evidence and clinical experience.”
  • The 10th St. Gallen (Switzerland) expert consensus meeting summary stated that “the Panel did not accept the molecularly based tools such as Oncotype DX™ …as sufficiently established to define risk categories.”

Thus, there is limited agreement that some women may benefit from using the results of the test to guide chemotherapy decisions. However, there are several limitations to the available evidence:

  • Among those willing to be guided by the test result, it is unknown what proportion of conventionally estimated intermediate- to high-risk patients will have sufficiently low RS values to change their decision regarding chemotherapy.
  • The recurrence risk level below which women are comfortable without chemotherapy is unknown; how the presentation of risk information affects choices is also unknown.
  • Women reclassified by RS result as intermediate or high risk from conventionally estimated low risk have a much wider range of recurrence risk estimates; women with very high RS values are likely to benefit from accepting chemotherapy, but for the intermediate-risk group benefits are uncertain.
  • Because the RS is a continuous function with respect to recurrence rates, risk category cutoff values selected by the test developer are arbitrary and may not be optimal.

In addition, some patient evaluation and treatment regimens in the validation studies differ from current practices. Patients in these studies were women younger than 70 years of age (or with a life expectancy of at least 10 years) who had unilateral, non-fixed, ER-positive, node-negative (by full axillary dissection) carcinomas and who were treated with surgery (mastectomy or lumpectomy), radiation therapy, and tamoxifen. In one trial, patients in the experimental arm were also treated with CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy. Current practices differ with respect to hormonal therapies, chemotherapy regimens, techniques for assessing lymph node status, and understanding of the role of progesterone receptor (PR) positivity.

Differences in current practices compared to the validation studies do not change our findings with respect to utility of gene expression profiling using Oncotype DX™. Aromatase inhibitor (AI)-based hormonal therapy instead of tamoxifen therapy would likely reduce recurrence rates for all RS risk groups. Thus, if a patient declined chemotherapy today on the basis of a low-risk RS (risk categories defined by outcomes after tamoxifen treatment), the even lower risk associated with AI treatment would not change that decision. For those receiving anthracycline-based chemotherapy instead of CMF, the type of chemotherapy does not change the interpretation of the Oncotype DX™ risk estimate. While current practice largely involves a detailed histologic examination of sentinel lymph nodes allowing for the detection of micrometastases (less than 2 mm in size), lymph nodes with micrometastases are not considered positive for purposes of treatment recommendations. Finally, only women with ER-positive tumors were enrolled in Oncotype DX™ validation studies, whereas current clinical guidelines include either ER or PR positivity in the treatment pathway for women with hormone-receptor-positive early breast cancer. Recent studies show that ER-negative, PR-positive patients also tend to benefit from hormonal therapy.

Many of these limitations and differences in treatment will be addressed by the TAILORx trial, currently underway (total accrual goal ~10,000). This trial will determine disease recurrence outcomes of RS intermediate patients (RS 11–25, ~44%) in particular by randomizing ER- and/or PR-positive, lymph-node-negative (by current methods) patients with intermediate-risk RS results to hormonal therapy (either tamoxifen or AI-based) plus chemotherapy versus hormonal therapy alone. Low-risk patients (RS<11, ~29%; treated only with hormonal therapy) will also be followed and compared to a prespecified target of no more than 5% recurrence at 10 years. The high-risk group (RS>25, ~27%) is assumed to benefit from chemotherapy. However, the TAILORx protocol uses more conservative cutoff values to define low- and high-risk patients than used in assay validation studies, in order to help define optimal cutoff values.

The TAILORx trial is not enrolling hormone-receptor-positive, early breast cancer patients whose disease is also HER2 positive. For these patients, the current NCCN guidelines recommend a different treatment pathway once the tumor measures 1 cm or more. Published trials of trastuzumab therapy have all included concurrent chemotherapy treatment and enrolled patients with a minimum tumor size of 1 cm or more. For these patients, trial outcomes have resulted in recommendations for trastuzumab and chemotherapy in addition to hormonal therapy. Therefore, because a choice regarding chemotherapy is not indicated, these patients are not candidates for Oncotype DX™. However, as noted in the summary of the most recent St. Gallen consensus conference and resulting guideline, “The role of trastuzumab in patients with small, endocrine responsive tumors and no axillary node involvement has not been adequately evaluated.” Thus, patients with hormone-receptor- and HER2-positive tumors that are smaller than 1 cm may need to decide whether to undergo chemotherapy alone and might be considered candidates for Oncotype DX™. It should be noted, however, that HER2 is represented in the Oncotype DX panel and RS results for the limited number of HER2-positive patients in one study were all categorized as intermediate or high risk.

MammaPrint®. There is insufficient evidence to determine whether MammaPrint® is better than conventional risk assessment tools in predicting recurrence. The 10-year disease-free survival rate of patients classified as low risk was 88-89%, with lower confidence limits of 74–77%, likely too low for most patients and physicians to consider forgoing chemotherapy. One reclassification study suggests that MammaPrint® adds additional information to one conventional risk classifier; ROC analysis suggests only a small improvement with MammaPrint® classification compared to a conventional classifier. Neither ASCO, NCCN, nor St. Gallen guidelines recommend the use of MammaPrint®. A prospective, randomized trial (MINDACT) is underway to evaluate outcomes of using MammaPrint® to guide treatment.

Breast Cancer Gene Expression Ratio. There is insufficient evidence to determine whether the Breast Cancer Gene Expression Ratio is better than conventional risk assessment tools in predicting recurrence. Recurrence rates of patients classified as low risk in available studies were 17–25%, likely too high for most patients and physicians to consider forgoing chemotherapy. There are no reclassification studies to directly compare the Breast Cancer Gene Expression Ratio with conventional risk classifiers. Neither ASCO, NCCN, nor St. Gallen guidelines recommend the use of the Breast Cancer Gene Expression Ratio.

Based on the available evidence, the Blue Cross and Blue Shield Association Medical Advisory Panel made the following judgments about whether gene expression profiling for managing breast cancer treatment meets the Blue Cross and Blue Shield Association Technology Evaluation Center (TEC) criteria.

1. The technology must have final approval from the appropriate governmental regulatory bodies.

Of the three gene expression profiles commercially available in the U.S., only MammaPrint® has been cleared by the FDA (cleared February 6, 2007). MammaPrint is the first cleared “in vitro diagnostic multivariate index assay” (IVDMIA). On September 7, 2006, the FDA issued new draft guidance for IVDMIAs; subsequent to extensive public commentary, a second draft guidance was issued on July 26, 2007 (http://www.fda.gov/cdrh/oivd/guidance/1610.pdf). In the latter document, an IVDMIA is defined as one that “1) Combines the values of multiple variables using an interpretation function to yield a single, patient-specific result (e.g., a “classification,” “score,” “index,” etc.), that is intended for use in the diagnosis of disease or other conditions, or in the cure, mitigation, treatment or prevention of disease, and 2) Provides a result whose derivation is non-transparent and cannot be independently derived or verified by the end user.” The comment period for the second IVDMIA draft guidance has ended, but the final disposition of the guidance is unknown at the time of this writing.

Oncotype DX™ and the Breast Cancer Gene Expression Ratio are each available from only one laboratory and are not cleared by the FDA. Clinical laboratories may develop and validate tests in-house (laboratory-developed tests or LDTs; previously called “home-brew”) and market them as a laboratory service; LDTs must meet the general regulatory standards of the Clinical Laboratory Improvement Act (CLIA). Laboratories offering the service must be licensed by CLIA for high-complexity testing. While the FDA has technical authority to regulate LDTs, to date, there has been no active oversight, with the new exception of IVDMIA devices.

Gene expression tests that are currently being marketed for clinical use or are being used in research protocols classify patients into disease risk or treatment response categories using algorithms that incorporate the tumor expression status of multiple genes. As such, most or all of these assays are likely to fall into the IVDMIA category. Thus, it is expected that Oncotype DX™ and possibly the Breast Cancer Gene Expression Ratio would need to meet the final pre- and postmarketing device requirements once the guidance document is finalized.

In general, FDA review of laboratory tests focuses largely on technical performance, assuring the reliability of test results over time. Review of clinical performance is more limited and may be based on “existing clinical data, new clinical trial data, review of information in the literature, or current clinical knowledge” (FDA Office of In Vitro Diagnostics 510(k) Workshop, April 19-20, 2005).

2. The scientific evidence must permit conclusions concerning the effect of the technology on health outcomes.

Oncotype DX.™ The evidence is sufficient to permit conclusions regarding health outcomes. Technical performance of the assay is well documented and is unlikely to be a major source of variability; rather, tissue sampling is likely the greatest source of variability. Retrospective epidemiologic analyses indicate strong, independent associations between Oncotype DX™ RS result and distant disease recurrence or death from breast cancer. The evidence identifies a subset of conventionally classified, high-risk patients who are at sufficiently low risk of recurrence by Oncotype DX™ that they might reasonably decide that the harms (toxicity) of chemotherapy outweigh the very small absolute benefit. Two studies of the original validation data, in which conventionally classified patients were reclassified by Oncotype DX™ result, indicate that the test provides significant recurrence risk information in addition to conventional criteria for individual patient risk classification. Additional evidence indicates that Oncotype DX™ results are significantly associated with breast cancer death in a community-based patient population, and that RS high-risk patients clearly benefit from chemotherapy, whereas benefits for other RS categories are not statistically significant.

MammaPrint®. There is 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. The 10-year disease-free survival rate of patients classified as low risk was 88–89%, with lower confidence limits of 74–77%, likely too high for most patients and physicians to consider forgoing chemotherapy. One reclassification study suggests that MammaPrint® adds additional information to one conventional risk classifier; ROC analysis suggests only a small improvement with MammaPrint® classification compared to a conventional classifier.

Breast Cancer Gene Expression Ratio. There is insufficient evidence to determine whether the Breast Cancer Gene Expression Ratio is better than conventional risk assessment tools in predicting recurrence. Assay configuration and performance characteristics of the commercially available version of the test have not been published. Recurrence rates of patients classified as low risk in available studies were 17–25%, likely too high for most patients and physicians to consider forgoing chemotherapy. There are no reclassification studies to directly compare the Breast Cancer Gene Expression Ratio with conventional risk classifiers.

3. The technology must improve the net health outcome; and
4. The technology must be as beneficial as any established alternatives.

Oncotype DX.™ Oncotype DX™ gene expression profiling can improve net health outcome in women with unilateral, non-fixed, hormone receptor-positive, node-negative breast cancer. In a significant subset of cases, Oncotype DX™ is likely to change the therapy decisions a patient and her physician would otherwise make using conventional risk classifiers. Women whose Oncotype DX™ RS value shows that they are at very low risk of recurrence might reasonably choose to forgo the harms and inconvenience of chemotherapy. The lower the RS value, the greater the confidence that the woman can have that chemotherapy will not provide net benefit, thus improving outcomes. Several limitations to the available evidence indicate the need for additional study.

MammaPrint® and Breast Cancer Gene Expression Ratio. The evidence is insufficient to permit conclusions as to whether the use of MammaPrint® or the Breast Cancer Gene Expression Ratio to determine recurrence risk for deciding whether or not to undergo adjuvant chemotherapy improves net health outcomes in women with early stage breast cancer.

5. The improvement must be attainable outside the investigational settings.

For Oncotype DX™, there is a single-source laboratory conducting the test; this laboratory also performed the tests for the validation studies. It is expected that the quality of diagnostic performance obtained in practice should be similar to that obtained in the published studies; however, the effect of increased demand for the test on the capacity of a single-source laboratory is unknown.

Whether MammaPrint® or the Breast Cancer Gene Expression Ratio improves the net health outcome has not been established in the investigational setting.

Based on the above, the use of Oncotype DX™ to determine recurrence risk for deciding whether or not to undergo adjuvant chemotherapy in women with unilateral, non-fixed, hormone-receptor-positive, node-negative breast cancer who will receive hormonal therapy meets the TEC criteria. The use of MammaPrint® or the Breast Cancer Gene Expression Ratio to determine recurrence risk in women with early stage breast cancer does not meet the TEC criteria.

FULL STUDY

Gene Expression Profiling of Breast Cancer to Select Women for Adjuvant Chemotherapy

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TEC Assessment Index

NOTICE OF PURPOSE:TEC Assessments are scientific opinions, provided solely for informational purposes. TEC Assessments should not be construed to suggest that the Blue Cross Blue Shield Association, Kaiser Permanente Medical Care Program or the TEC Program recommends, advocates, requires, encourages, or discourages any particular treatment, procedure, or service; any particular course of treatment, procedure, or service; or the payment or non-payment of the technology or technologies evaluated.

KEYWORDS: adjuvant; Adjuvant! Online; AI; Amsterdam; analyte specific reagents; analyte-specific; analytic validity; aromatase inhibitor; ASCO; ASR; assay kit; breast cancer, Breast Cancer Gene Expression Ratio; estrogen receptor; cancer; cDNA; chemohormonal therapy; chemotherapy; clinical utility; clinical validity; complimentary; gene expression panel; gene signature; genetic test; genetic testing; Genomic Health; genomics; guideline; guidelines; home brew; homebrew; in vitro diagnostic multivariate index assay; IVDMIA; MammaPrint; microarray; microarray; MINDACT; morbidity; mortality; multigene; multi-gene; National Comprehensive Cancer Network; National Surgical Adjuvant Breast and Bowel Project; NCCN; negative; neoadjuvant; node negative; node-negative; NSABP; oncology; Oncotype DX; polychemotherapy; positive; prediction; prognosis; recurrence; recurrence score; RS; St. Gallen; tamoxifen; TRANS-BIG; tumor grade; tumor makers; tumor size; tumor; validation; women’s health;