scholarly journals A 95-gene Signature Stratifies Recurrence Risk of Invasive Disease in ER-positive, HER2-negative, Node-negative Breast Cancer With Intermediate 21-gene Signature Recurrence Scores

2021 ◽  
Author(s):  
Takeo Fujii ◽  
Hiroko Masuda ◽  
Yee Chung Cheng ◽  
Fei Yang ◽  
Aysegul A. Sahin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Gene Signature ◽  
Invasive Disease ◽  
Cytotoxic Agents ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Er Positive ◽  
Chemoendocrine Therapy

Abstract Purpose A subset of patients with intermediate 21-gene signature assay recurrence score may benefit from adjuvant chemoendocrine therapy, but a predictive strategy is needed to identify such patients. The 95-gene signature assay was tested to stratify patients with intermediate RS into high (95GC-H) and low (95GC-L) groups that were associated with invasive recurrence risk.Methods Patients with ER-positive, HER2-negative, node-negative breast cancer and RS 11-25 who underwent definitive surgery and adjuvant endocrine therapy without any cytotoxic agents were included. RNA was extracted from archived formalin-fixed, paraffin-embedded samples, and 95-gene signature was calculated. Results Two hundred six patients had RS of 11-25 (95GC-L, N = 163; 95GC-H, N = 43). In Cox proportional hazards model, 95GC-H was significantly associated with shorter time to recurrence than was 95GC-L (HR 5.94; 95%CI 1.81-19.53; P = 0.005). The correlation between 95-gene signature and 21-gene signature assay scores was not strong (correlation coefficient r = 0.27), which might suggest that 95-gene signature reflects biological characteristics differing from what 21-gene signature shows.Conclusions The 95-gene signature stratifies patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS of 11-25 into high and low groups that are associated with recurrence risk of invasive disease. Further retrospective analysis in the prospectively-accrued TAILORx population is warranted to confirm that 95-gene signature can identify patients who would benefit from adjuvant chemoendocrine therapy.

A novel 95-gene signature (Curebest 95GC Breast) that predicts recurrence-risk in patients with ER-positive, HER2-negative, node-negative, early-stage primary invasive breast cancer with an intermediate Oncotype DX Recurrence Score.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 542-542
Author(s):  
Takeo Fujii ◽  
Hiroko Masuda ◽  
Yee Chung Cheng ◽  
Fei Yang ◽  
Aysegul A. Sahin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Invasive Breast Cancer ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Gene Signature ◽  
Oncotype Dx ◽  
Node Negative ◽  
Er Positive ◽  
Chemoendocrine Therapy ◽  
Oncotype Dx Recurrence Score

542 Background: The TAILORx trial demonstrated that adjuvant endocrine and chemoendocrine therapies had similar efficacy in patients with hormone receptor-positive, HER2-negative, node-negative breast cancer with an Oncotype DX recurrence score (RS) of 11-25. However, a predictive strategy is needed to identify patients with intermediate RS who may benefit from adjuvant chemoendocrine therapy. Curebest 95GC Breast (95GC) is a 95-gene signature that can stratify patients into two groups with high (95GC-H) and low (95GC-L) groups to predict the risk of recurrence. Our primary objective was to show that 95GC can classify patients with intermediate RS into binary recurrence risk groups. Methods: Patients with ER-positive, HER2-negative, node-negative invasive breast cancer and RS 11-30 who underwent definitive surgery and adjuvant endocrine therapy were included. RNA was derived from archived formalin-fixed, paraffin-embedded samples, and 95GC was calculated as reported previously. The Fisher exact and Brunner-Munzel tests were used to compare variables between 95GC groups. A Kaplan-Meier estimate with a log-rank test was used for recurrence-free survival (RFS) analysis. Results: The analysis included 178 patients from five institutions. The 5-year RFS rate in patients with RS 18-30 was higher in the 95GC-L group (n = 129, 96.3%) than in the 95GC-H group (n = 49, 90.9%; p = 0.002), which was consistent with results in an independent Japanese population (n = 224; p < 0.001). RFS rates significantly differed between the groups among patients with RS 11-25 as well (95GC-L, 97.4%; 95GC-H, 87.1%; p = 0.001). RFS rates did not differ between patients with RS 18-25 (94.8%) and those with RS 26-30 (93.8%; p = 0.33). Conclusions: 95GC can predict recurrence risk in patients with ER-positive, HER2-negative, node-negative invasive breast cancer and intermediate RS. Further prospective retrospective studies in the TAILORx population are warranted to confirm that 95GC can identify patients who may benefit from adjuvant chemoendocrine therapy.

Cost Effectiveness of Molecular Profiling for Adjuvant Decision Making in Patients With Node-Negative Breast Cancer

2014 ◽  
Vol 32 (31) ◽  
pp. 3513-3519 ◽  
Author(s):  
Julia Bonastre ◽  
Sophie Marguet ◽  
Beranger Lueza ◽  
Stefan Michiels ◽  
Suzette Delaloge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Decision Making ◽  
Cost Effectiveness ◽  
Adjuvant Chemotherapy ◽  
Cost Effective ◽  
Gene Signature ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Life Years ◽  
Er Positive

Purpose To conduct an economic evaluation of the 70-gene signature used to guide adjuvant chemotherapy decision making both in patients with node-negative breast cancer (NNBC) and in the subgroup of estrogen receptor (ER) –positive patients. Patients and Methods We used a mixed approach combining patient-level data from a multicenter validation study of the 70-gene signature (untreated patients) and secondary sources for chemotherapy efficacy, unit costs, and utility values. Three strategies on which to base the decision to administer adjuvant chemotherapy were compared: the 70-gene signature, Adjuvant! Online, and chemotherapy in all patients. In the base-case analysis, costs from the French National Insurance Scheme, life-years (LYs), and quality-adjusted life-years (QALYs) were computed for the three strategies over a 10-year period. Cost-effectiveness acceptability curves using the net monetary benefit were computed, combining bootstrap and probabilistic sensitivity analyses. Results The mean differences in LYs and QALYs were similar between the three strategies. The 70-gene signature strategy was associated with a higher cost, with a mean difference of €2,037 (range, €1,472 to €2,515) compared with Adjuvant! Online and of €657 (95% CI, −€642 to €3,130) compared with systematic chemotherapy. For a €50,000 per QALY willingness-to-pay threshold, the probability of being the most cost-effective strategy was 92% (76% in ER-positive patients) for the Adjuvant! Online strategy, 6% (4% in ER-positive patients) for the systematic chemotherapy strategy, and 2% (20% in ER-positive patients) for the 70-gene strategy. Conclusion Optimizing adjuvant chemotherapy decision making based on the 70-gene signature is unlikely to be cost effective in patients with NNBC.

A novel approach for 21-genes testing associated with prognosis in Chinese patients with ER-positive/HER2-negative breast cancer: A real-world study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12528-e12528
Author(s):  
Yinduo Zeng ◽  
Qian Li ◽  
Jiannan Wu ◽  
Heran Deng ◽  
Ying Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Recurrence Score ◽  
Risk Groups ◽  
Chinese Version ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Er Positive ◽  
The Impact

e12528 Background: We previously reported a Chinese version of 21-genes Recurrence Score (RS) provides reduction chemotherapy prescription in patients with ER-Positive/HER2-Negative node negative breast cancer, while Oncotype Dx was hardly to be reached. However, the impact on clinical outcome was not mentioned. Herein, we explored whether this 21-genes recurrence score (RS) impacted on prognosis in patients with this molecular subtype of breast cancer. Methods: From Jan 2013 to Aug 2018, 378 patients with ER-Positive/HER2-Negative early stage breast cancer were enrolled. All patients received a Chinese version of 21-genes RS test, which is a new method using RNA extracted from formalin-fixed paraffin-embedded tissue performed by SurExam Campany, Guangzhou, China. . The RS score for each patient was calculated based on expression level of 21-genes used in a prosperctively defined algorithm and calculate a recurrence score range from 0 to 100 and divided three risk groups according to TAILORs study.Distant metastases-free survival (DMFS) were correlated with the 21-genes RS by Kaplan-Meier (log-rank method), and Cox regression. Multivariable logistic regression was performed to determine factors correlated with RS testing and receipt of a high-risk RS. Results: Median patient age was 46 years (18 to 77 years). The Chinese version of 21-gene RS was generated for 378 patients: 61 (16.1%) low risk ( < 11), 241 (63.8%) intermediate risk (11 to 25), and 76 (20.1%) high risk (≥ 26). At a median follow-up of 40 months, the 4-year-rate of estimated DMFS was 100%, 98.7% and 92.9% in low risk, intermediate risk and high risk groups. Meanwhile, there was no difference in RFS among three risk groups. For all patients, 21-gene RS was associated with DMFS ( P = .021). In multivariable Cox regression models, 21-gene RS was independently prognostic factor of DMFS (hazard ratio, 5.375; 95% CI, 1.00 to 28.84; P = .05). Tumor size (>2cm vs ≤2cm, OR = 2.31, P = .005), high grade ( OR = 2.15, P = .013), ki67 index ( > 14% vs ≤14%, OR = 4.24, P = .002), progesterone receptor expression ( < 20% vs ≥20%, OR = 5.07, P < .001) were predictor of high risk of RS. Conclusions: The Chinese version of 21-genes RS is independently prognostic factor for DMFS patients with ER–positive/HER2-negative node negative breast cancer. Future study was needed to explore the impact of 21 gene RS on long-term prognosis.

A comparative analysis of distant recurrence risk assessments by Oncotype DX recurrence score alone and integrated with clinicopathologic factors in early-stage breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 598-598 ◽  
Author(s):  
Ciara Marie Kelly ◽  
Rose Beamish ◽  
John McCaffrey ◽  
Martina SMITH ◽  
John Crown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recurrence Score ◽  
Risk Groups ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
Oncotype Dx ◽  
Node Negative ◽  
Er Positive ◽  
Clinicopathologic Factors ◽  
Oncotype Dx Recurrence Score

598 Background: Treatment planning for patients with node negative, ER-positive, HER-2 negative breast cancer often incorporates the use of prognostic and predictive tools like Oncotype DX. Prior to the availabilty of Oncotype DX, clinicopathologic factors such as age, nodal status, tumour size and grade were used to determine risk of recurrence (ROR). RSPC represents a validated formal integration of oncotype DX recurrence score (RS) and clinicopathologic factors that further refines prognostic accuracy. RSPC does not improve the prediction of likelihood of chemotherapy benefit. The objective of this study was to compare distant recurrence risk assessment by RS and RSPC. Methods: We included patients with node negative, ER-positive, HER2-negative breast cancer who had Oncotype DX testing routinely or on clinical trial. We retrospectively reviewed patient charts and extracted clinicopathological and RS data. We calculated the RSPC using the RSPC educational tool. A comparative analysis was performed looking at the statification of patients into low (LR), intermediate (IR) and high (HR) ROR groups by RS and RSPC. The cut offs for low, intermediate and high risk by the RSPC were set to less than 12%, 12-20% and more than 20% risk of distant recurrence at 10yrs, corresponding to the risks of recurrence associated with the RS categories. Results: We identified 658 patients from 5 academic hospitals in Ireland and the US. Oncotype DX RS classified the following proportions of patients into three risk groups for distant recurrence: LR, n=334 (50.5%), IR, n=259 (39.4%), HR, n=67 (10.1%). RSPC classified the following proportion of patients into the three risk groups for recurrence: LR, n= 455 (69.1%), IR, n=110 (16.7%), HR, n=93 (14.1%). RSPC reclassified 72.6% (n=188) of the IR group (59.1% (n=153) from IR to LR and 13.5% (n=35) from IR to HR). RPSC reclassified 10.5% (n=35) of the LR group (8.1% (n=27) from LR to IR, and 2.4% (n=8) from LR to HR). RSPC reclassified 25.3% (n=17) of the HR group (17.9% (n=12) from HR to IR, and 7.4% (n=5) from HR to LR). Conclusions: RSPC reclassified 240 patients (36.5%) and was most helpful reassigning the IR group.

scholarly journals Risk of Recurrence and Chemotherapy Benefit for Patients With Node-Negative, Estrogen Receptor–Positive Breast Cancer: Recurrence Score Alone and Integrated With Pathologic and Clinical Factors

2011 ◽  
Vol 29 (33) ◽  
pp. 4365-4372 ◽  
Author(s):  
Gong Tang ◽  
Jack Cuzick ◽  
Joseph P. Costantino ◽  
Mitch Dowsett ◽  
John F. Forbes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
Risk Assessments ◽  
Intermediate Risk ◽  
Clinical Factors ◽  
Node Negative ◽  
Er Positive ◽  
Positive Breast Cancer

Purpose The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) –positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. Patients and Methods From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. Results RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). Conclusion RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.

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