scholarly journals Analytical Validation of the Oncotype DX Genomic Diagnostic Test for Recurrence Prognosis and Therapeutic Response Prediction in Node-Negative, Estrogen Receptor–Positive Breast Cancer

2007 ◽  
Vol 53 (6) ◽  
pp. 1084-1091 ◽  
Author(s):  
Maureen Cronin ◽  
Chithra Sangli ◽  
Mei-Lan Liu ◽  
Mylan Pho ◽  
Debjani Dutta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Oncotype Dx ◽  
Analytical Performance ◽  
Performance Criteria ◽  
Operational Performance ◽  
Node Negative ◽  
Unit Scale ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

Abstract Background: Oncotype DX™ is a clinically validated, high-complexity, multianalyte reverse transcription–PCR genomic test that predicts the likelihood of breast cancer recurrence in early-stage, node-negative, estrogen receptor–positive breast cancer. The Recurrence Score™ (RS) provides a more accurate, reproducible measure of breast cancer aggressiveness and therapeutic responsiveness than standard measures. Individualized patient management requires strict performance criteria for clinical laboratory tests. We therefore investigated the analytical performance of the assay. Methods: Assays used a pooled RNA sample from fixed paraffin-embedded tissues to evaluate the analytical performance of a 21-gene panel with respect to amplification efficiency, precision, linearity, and dynamic range, as well as limits of detection and quantification. Performance variables were estimated from assays carried out with sample dilutions. In addition, individual patient samples were used to test the optimized assay for reproducibility and sources of imprecision. Results: Assay results defined acceptable operational performance ranges, including an estimated maximum deviation from linearity of <1 cycle threshold (CT) units over a ≥2000-fold range of RNA concentrations, with a mean quantification bias of 0.3% and CVs of 3.2%–5.7%. An analysis of study design showed that assay imprecision contributed by instrument, operator, reagent, and day-to-day baseline variation was low, with SDs of <0.5 CT. Conclusion: The analytical and operational performance specifications defined for the Oncotype DX assay allow the reporting of quantitative RS values for individual patients with an SD within 2 RS units on a 100-unit scale.

Cost-effectiveness of the 21-gene recurrence score assay in the setting of multifactorial decision making for chemotherapy in early-stage breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1525-1525
Author(s):  
Shelby D. Reed ◽  
Michaela A Dinan ◽  
Kevin A. Schulman ◽  
Gary H. Lyman
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Estrogen Receptor ◽  
Cost Effectiveness ◽  
Recurrence Score ◽  
Risk Groups ◽  
The United States ◽  
Node Negative ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

1525 Background: The objective of this study was to incorporate evidence from two recently-published studies to reevaluate the cost-effectiveness of the 21-gene Recurrence Score (RS) assay (Oncotype DX) in the context of multifactorial decision making to guide the use of chemotherapy for node-negative, estrogen receptor–positive breast cancer in the United States from the societal and healthcare system perspectives. Methods: We developed a decision-analytic model to first cross-classify hypothetical patients by clinicopathologic characteristics according to the Adjuvant! using risk groups and RS risk groups. We generated estimates of long-term costs, survival, and quality-adjusted survival for the RS-guided and non–RS-guided strategies using a probabilistic state transition model. In addition to costs for the 21-gene assay, we assigned attributable costs for chemotherapy, hormonal therapy, monitoring for disease recurrence, and distant recurrence. For the societal perspective, we also considered incremental patient time costs. Costs and survival were discounted at 3% annually. Results: With the RS-guided strategy, 40.4% of patients were expected to receive chemotherapy relative to 47.3% in the non–RS-guided strategy. Targeted use of chemotherapy in the RS-guided strategy was expected to increase survival by 0.19 years (95% CI, 0.09 to 0.32) and 0.16 QALYs (95% CI, 0.08 to 0.28). Lifetime direct medical costs were expected to be $2692 (95% CI, 1546 to 3821) higher with the RS-guided strategy. The incremental cost-effectiveness ratios (ICERs) were $14,059 per life-year saved (95% CI, $6840-$28,912) and $16,677 per QALY (95% CI, $7613-$37,219). When incorporating lower indirect costs of $950 per patient, the ICERs were $9095 per life-year saved (95% CI, dominant-$23,397) and $10,788 per QALY (95% CI, $6840-$30,265). In probabilistic sensitivity analysis, more than 99% of the ICERs were less than $50,000 per life-year saved and per QALY. Conclusions: Our updated cost-effectiveness estimates are supportive of the economic value of the 21-gene RS assay in the setting of node-negative, estrogen receptor–positive breast cancer.

Can Features Evaluated in the Routine Pathologic Assessment of Lymph Node–Negative Estrogen Receptor–Positive Stage I or II Invasive Breast Cancer Be Used to Predict the Oncotype DX Recurrence Score?

2010 ◽  
Vol 134 (11) ◽  
pp. 1697-1701
Author(s):  
Jena Auerbach ◽  
Mimi Kim ◽  
Susan Fineberg
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Lymph Node ◽  
Invasive Breast Cancer ◽  
Recurrence Score ◽  
Mitotic Count ◽  
Oncotype Dx ◽  
Node Negative ◽  
Estrogen Receptor Positive ◽  
Pathologic Assessment

Abstract Context.—Oncotype DX is a multigene reverse transcription–polymerase chain reaction assay used to quantify recurrence risk in patients with stage I or II estrogen receptor–positive, lymph node–negative invasive breast cancer. The results are reported as a Recurrence Score (RS). The 16 cancer genes evaluated include a proliferation set, hormone receptor set, and HER2 set. The activity of these genes is addressed by pathologic assessment of breast cancers. Objective.—To determine if factors evaluated in pathologic evaluation of breast cancer could be used to predict Oncotype DX results. Design.—We studied 138 cases of invasive breast cancer for which Oncotype DX results and pathology data were available. Grading was performed by using Nottingham grading system. For hormone receptor immunostaining, 10% nuclear staining was considered a positive result. Results.—Oncotype DX RS was low in 81 cases, intermediate in 44 cases, and high in 13 cases. All 6 cases with both a negative progesterone receptor (PR) and a mitotic count score of 3 had a high RS. All 12 cases with both a negative PR and a mitotic count score greater than 1 had either an intermediate or high RS. Although Nottingham grade, PR status, mitotic count score, tumor size, and nuclear grade were each significantly associated with RS, in bivariate analyses the only variables that remained independently predictive of an intermediate or high RS score in a multivariate logistic regression model were negative PR and mitotic count score greater than 1. Conclusions.—Our study suggests that a mitotic count score greater than 1 combined with a negative PR result, as determined by pathologic assessment, could serve as a marker for an intermediate or high Oncotype DX RS.

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