Gene Expression and Benefit of Chemotherapy in Women With Node-Negative, Estrogen Receptor–Positive Breast Cancer

2006 ◽  
Vol 24 (23) ◽  
pp. 3726-3734 ◽  
Author(s):  
Soonmyung Paik ◽  
Gong Tang ◽  
Steven Shak ◽  
Chungyeul Kim ◽  
Joffre Baker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Relative Risk ◽  
Distant Recurrence ◽  
Chemotherapy Treatment ◽  
Node Negative ◽  
Estrogen Receptor Positive ◽  
Large Benefit ◽  
Absolute Decrease ◽  
Positive Breast Cancer

Purpose The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor–positive, lymph node–negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. Methods The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy–treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. Results A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (≥ 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, −1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. Conclusion The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor–positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

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 &lt;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 &lt;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.

scholarly journals 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

2010 ◽  
Vol 28 (10) ◽  
pp. 1677-1683 ◽  
Author(s):  
Eleftherios P. Mamounas ◽  
Gong Tang ◽  
Bernard Fisher ◽  
Soonmyung Paik ◽  
Steven Shak ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Locoregional Recurrence ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Locoregional Therapy ◽  
Second Primary ◽  
Node Negative ◽  
Er Positive ◽  
Positive Breast Cancer

Purpose The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)–positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20). Patients and Methods RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored. Results In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P < .001). The 10-year Kaplan-Meier estimate of LRR was 4.% (95% CI, 2.3% to 6.3%) for patients with a low RS (< 18), 7.2% (95% CI, 3.4% to 11.0%) for those with intermediate RS (18-30), and 15.8% (95% CI, 10.4% to 21.2%) for those with a high RS (> 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen–treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment. Conclusion Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer.

Sign in / Sign up

Export Citation Format

Share Document