Comparison of StemPrintER, a novel biology-based genomic predictor of distant recurrence in breast cancer, with Oncotype DX in the TransATAC cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1020-1020
Author(s):  
Salvatore Pece ◽  
Ivana Sestak ◽  
Francesca Montani ◽  
Micol Tillhon ◽  
Stefano Freddi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Decision Making ◽  
Early Stage ◽  
Recurrence Score ◽  
Risk Groups ◽  
Recurrence Risk ◽  
Continuous Variable ◽  
Clinicopathological Parameters ◽  
Prognostic Information ◽  
Her2 Breast Cancer

1020 Background: Accurate prediction of distant metastasis (DM) in early stage ER+/HER2- breast cancer (BC) patients is vital to avoid over/under-treatment with adjuvant chemotherapy (CT). The OncotypeDX Recurrence Score (RS) is a widely used tool to assist clinical decision-making for CT. The StemPrintER Risk Score (SPRS) is an alternative genomic predictor based on the biology of cancer stem cells that predicts recurrence risk in ER+/HER2- BCs (Pece S. et al., EBioMedicine 2019). Here, we analyze the prognostic value of SPRS in the TransATAC cohort of post-menopausal ER+/HER2- BC patients, and compare the prognostic information provided by SPRS and RS for 10-year risk of DM. Methods: The likelihood χ2 (LRχ2) and Kaplan-Meier survival analyses were used to assess prognostic information provided by SPRS, RS and the clinical treatment score (CTS) in 818 TransATAC patients treated with anastrozole or tamoxifen for 5 years. Comparative analyses were made for DM risk over the 10-year follow-up, as well as in the early (0-5 years) or late (5-10 years) interval, according to nodal status. Results: Used as a continuous variable, SPRS was an independent predictor of DM in years 0-10 among all patients when adjusted for clinical parameters as expressed by the CTS [HR=1.43 (1.18-1.73), P<0.0001], as well as in node-negative [HR=1.51 (1.17-1.94), P=0.001] but not node-positive (N1-3) patients [HR=1.29 (0.95-1.75), P=0.11]. A predefined SPRS cut-off was used to stratify patients into low vs. high risk groups [LOW: N=454, 10-year DM rate=5.8%; HIGH: N=364, 10-year DM rate=21.9%; HRHIGH vs. LOW=2.96 (1.85-4.73); P<0.0001]. SPRS outperformed RS in providing prognostic information for 10-year DM risk (SPRS: HR=1.79, P<0.0001, LRχ2=33.4; RS: HR=1.52, P<0.0001, LRχ2=22.1), with even greater differences in late DM prediction in N0 patients. SPRS also provided more prognostic information than RS to CTS (ΔLRχ2: SPRS+CTS vs. CTS= 14.9; RS+CTS vs. CTS= 9.7). Conclusions: In ER+/HER2- TransATAC BC patients, SPRS was highly prognostic for DM and was superior to RS in providing additional prognostic information to conventional clinicopathological parameters.

scholarly journals Development and validation for research assessment of Oncotype DX® Breast Recurrence Score, EndoPredict® and Prosigna®

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Richard Buus ◽  
Zsolt Szijgyarto ◽  
Eugene F. Schuster ◽  
Hui Xiao ◽  
Ben P. Haynes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Early Stage ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Research Assessment ◽  
Expression Data ◽  
Her2 Breast Cancer ◽  
Validation Set ◽  
Development And Validation

AbstractMulti-gene prognostic signatures including the Oncotype® DX Recurrence Score (RS), EndoPredict® (EP) and Prosigna® (Risk Of Recurrence, ROR) are widely used to predict the likelihood of distant recurrence in patients with oestrogen-receptor-positive (ER+), HER2-negative breast cancer. Here, we describe the development and validation of methods to recapitulate RS, EP and ROR scores from NanoString expression data. RNA was available from 107 tumours from postmenopausal women with early-stage, ER+, HER2− breast cancer from the translational Arimidex, Tamoxifen, Alone or in Combination study (TransATAC) where previously these signatures had been assessed with commercial methodology. Gene expression was measured using NanoString nCounter. For RS and EP, conversion factors to adjust for cross-platform variation were estimated using linear regression. For ROR, the steps to perform subgroup-specific normalisation of the gene expression data and calibration factors to calculate the 46-gene ROR score were assessed and verified. Training with bootstrapping (n = 59) was followed by validation (n = 48) using adjusted, research use only (RUO) NanoString-based algorithms. In the validation set, there was excellent concordance between the RUO scores and their commercial counterparts (rc(RS) = 0.96, 95% CI 0.93–0.97 with level of agreement (LoA) of −7.69 to 8.12; rc(EP) = 0.97, 95% CI 0.96–0.98 with LoA of −0.64 to 1.26 and rc(ROR) = 0.97 (95% CI 0.94–0.98) with LoA of −8.65 to 10.54). There was also a strong agreement in risk stratification: (RS: κ = 0.86, p < 0.0001; EP: κ = 0.87, p < 0.0001; ROR: κ = 0.92, p < 0.001). In conclusion, the calibrated algorithms recapitulate the commercial RS and EP scores on individual biopsies and ROR scores on samples based on subgroup-centreing method using NanoString expression data.

Comparison of PAM50 Risk of Recurrence Score With Oncotype DX and IHC4 for Predicting Risk of Distant Recurrence After Endocrine Therapy

2013 ◽  
Vol 31 (22) ◽  
pp. 2783-2790 ◽  
Author(s):  
Mitch Dowsett ◽  
Ivana Sestak ◽  
Elena Lopez-Knowles ◽  
Kalvinder Sidhu ◽  
Anita K. Dunbier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Growth Factor Receptor ◽  
Recurrence Score ◽  
Risk Groups ◽  
Distant Recurrence ◽  
Oncotype Dx ◽  
Prognostic Information ◽  
Node Negative ◽  
Risk Of Recurrence ◽  
Er Positive

Purpose Risk of distant recurrence (DR) among women with estrogen receptor (ER) –positive early breast cancer is the major determinant of recommendations for or against chemotherapy. It is frequently estimated using the Oncotype DX recurrence score (RS). The PAM50 risk of recurrence (ROR) score provides an alternative approach, which also identifies intrinsic subtypes. Patients and Methods mRNA from 1,017 patients with ER-positive primary breast cancer treated with anastrozole or tamoxifen in the ATAC trial was assessed for ROR using the NanoString nCounter. Likelihood ratio (LR) tests and concordance indices (c indices) were used to assess the prognostic information provided beyond that of a clinical treatment score (CTS) by RS, ROR, or IHC4, an index of DR risk derived from immunohistochemical assessment of ER, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki67. Results ROR added significant prognostic information beyond CTS in all patients (Δ LR-χ2 = 33.9; P < .001) and in all four subgroups: node negative, node positive, HER2 negative, and HER2 negative/node negative; more information was added by ROR than by RS. C indices in the HER2-negative/node-negative subgroup were 0.73, 0.76, and 0.78 for CTS, CTS plus RS, and CTS plus ROR, respectively. More patients were scored as high risk and fewer as intermediate risk by ROR than by RS. Relatively similar prognostic information was added by ROR and IHC4 in all patients but more by ROR in the HER2-negative/node-negative group. Conclusion ROR provides more prognostic information in endocrine-treated patients with ER-positive, node-negative disease than RS, with better differentiation of intermediate- and higher-risk groups.

Adjuvant treatment decision in patients with node-negative, ER+/Her2-, early stage breast cancer with Oncotype DX (ODX) recurrence score (RS) of 11-30: Impact of clinicopathologic features.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12022-e12022
Author(s):  
Gwenalyn Garcia ◽  
Shiksha Kedia ◽  
Nishitha Thumallapally ◽  
Elias Moussaly ◽  
Saqib Abbasi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Early Stage ◽  
Univariate Analysis ◽  
Prospective Trial ◽  
Recurrence Score ◽  
Clinicopathologic Features ◽  
Node Negative ◽  
Her2 Breast Cancer ◽  
Node Negative Breast Cancer

e12022 Background: The ODX RS predicts the risk of distant recurrence and the benefit of adjuvant chemotherapy (CT) in patients with ER+/Her2- breast cancer. High RS predicts a large benefit whereas low RS predicts minimal benefit from CT. A prospective trial showed that patients with low RS of 0-10 may be safely spared adjuvant CT. Recommendations in patients with intermediate RS are less clear. We performed a retrospective study of adjuvant therapy decision in patients with RS 11-30. Methods: We identified patients with ER+/Her2-, node-negative breast cancer with ODX RS 11-30 treated at our center from 2010-2016. Data on patient age, type of surgery, tumor size, grade, lymphovascular invasion (LVI), RS and treatment were collected. Statistical associations were tested using Chi square/Fisher's exact test and t test. Logistic regression analysis was used to determine odds ratios (OR). Results: 76 patients were identified. 86% (65/76) of them received adjuvant endocrine therapy alone and 14% (11/76) received adjuvant CT plus endocrine therapy. Patient characteristics are shown in the table. Using univariate analysis, significant predictors of receiving CT included RS, LVI, and ER positivity. In the patients who received CT, RSs were all ≥ 18 whereas in the group who did not receive CT, 42% (27/65) patients had RS 11-17. Increase in RS was associated with increase in the likelihood of receiving CT (OR 1.40, 95% CI 1.14-1.74, p=0.00017). Decrease in ER positivity was correlated with increased likelihood of receiving CT (OR 0.922, 95% CI 0.856-0.992, p=0.03). The presence of LVI increased the likelihood of receiving CT (OR 26.24, 95% CI 4.16-165.43, p=0.0005). Conclusions: In patients with ER+/Her2-, node-negative breast cancer with RS 11-30, the majority received endocrine therapy alone. RS and some clinicopathologic features (LVI, ER) impacted the decision to receive CT. [Table: see text]

Breast Cancer Index and risk stratification in luminal subtypes: A trans-ATAC study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 534-534
Author(s):  
Ivana Sestak ◽  
Yi Zhang ◽  
Catherine A. Schnabel ◽  
Jack M. Cuzick ◽  
Mitchell Dowsett
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Cox Regression ◽  
Early Stage ◽  
Risk Groups ◽  
Low Risk ◽  
Luminal A ◽  
Prognostic Information ◽  
Prognostic Performance ◽  
Breast Cancer Index

534 Background: The Breast Cancer Index (BCI) is a gene-expression based signature that provides prognostic information for overall (0-10 years) and late (5-10 years) distant recurrence (DR) and prediction of extended endocrine benefit in hormone receptor positive (HR+) early stage breast cancer. The current analysis aims to further characterize, correlate and compare the prognostic performance of BCI in luminal subtypes based on immunohistochemical classification. Methods: 670 postmenopausal women with HR+, LN- disease from the TransATAC cohort were included in this analysis. Luminal A-like tumors (LumA) were identified as those with ER+ and/or PR+ and HER2 -, and Ki67 < 20% by IHC. All other tumors were classified as Luminal B-like (LumB) for this analysis. Primary endpoint was DR. Cox regression models were used to examine BCI prognostic performance according to luminal subtype, adjusting for the clinicopathological model Clinical Treatment Score (CTS). Results: 452 (67.5%) patients were classified as LumA and 218 (32.5%) as LumB. BCI was highly prognostic in LumA cancers (adjusted HR = 1.57 (1.23-1.96), P < 0.001, ΔLR-χ2= 14.09), but not in LumB tumors (adjusted HR = 1.20 (0.94-1.52, P = 0.14, ΔLR-χ2= 2.23). In LumA, 10-year DR risks in BCI intermediate and high risk groups were very similar (25.6% (16.4-38.6) and 25.3% (13.5-44.3), respectively) and significantly different from BCI low (3.9% (2.1-7.0); HR = 7.47 (3.50-15.96) and HR = 8.13 (3.27-20.23), respectively). In LumB, 10-year DR risks in BCI low and BCI intermediate risk groups (13.8% (6.8-26.9) and 14.6% (8.3-24.9), respectively) were very similar and significantly lower than for the BCI high (29.1% (20.0-41.1)). Lum subtyping was only prognostic in the BCI low risk group (LumA vs. LumB: HR = 4.27 (1.65-11.02)) but not in the other two BCI risk groups. Conclusions: BCI provided significant prognostic information in Lum A subtype. These results show that BCI intermediate and high risk had similar risk of DR in LumA tumors, while shared similarly low risk of DR as BCI-low in LumB tumors. Further evaluation is needed to elucidate the distinct mechanisms underlying each classification system.

Integration of the stem cell biology-based genomic tool, StemPrintER, with clinicopathological parameters for the prediction of distant recurrence in ER+/HER2- breast cancer (BC) patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 1057-1057
Author(s):  
Salvatore Pece ◽  
Patrick Maisonneuve ◽  
Davide Disalvatore ◽  
Stefano Freddi ◽  
Paolo Veronesi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Biology ◽  
Cox Regression ◽  
Nodal Status ◽  
Endocrine Treatment ◽  
Clinicopathological Parameters ◽  
Prognostic Information ◽  
Significant Information ◽  
Her2 Breast Cancer

1057 Background: The StemPrintER risk score (SPRS) is a 20 gene-based predictor that estimates the “degree of stemness” of the primary tumor and provides additional prognostic information regarding distant metastasis (DM) risk in early stage ER+/HER2- breast cancer (BC) patients beyond that obtained from standard clinicopathological parameters. Here we describe a further refined model, that combines prognostic information from SPRS with tumor size (pT) and nodal status (pN), termed SPARE (SPRS for Personalized Adjuvant therapy in Receptor-Expressing patients). SPARE was compared to the clinical treatment score (CTS) for 10-year risk of DM in a consecutive-retrospective ER+/HER2- BC patient cohort (n=1,827) with 15-year complete follow-up from the European Institute of Oncology (IEO) in Milan. Methods: The SPARE model was developed in patients randomly assigned to a training set (n=609), using the ridge-penalized Cox regression, and tested in an independent validation set (n=1,218). Likelihood χ2 (LRχ2) and Kaplan-Meier survival analysis were used to compare the prognostic information from SPARE and CTS (based on age, pN, pT, endocrine treatment). Comparative analyses were made for the DM risk over the 10-year follow-up, as well as in the early (0-5 years) or late (5-10 years) interval, according to nodal status. Results: SPARE outperformed CTS in providing prognostic information for 10-year DM risk (LRχ2: SPARE = 141.2, P<0.0001; CTS=118.1, P<0.0001), with even greater differences in node-negative patients (LRχ2: SPARE=47.6, P<0.0001; CTS=27.5, P<0.0001) and in 1-3 node-positive patients (LRχ2: SPARE=30.6, P<0.0001; CTS=15.1, P<0.0001). When reciprocally adjusted for each other, SPARE added prognostic information to CTS (ΔLRχ2: CTS+SPARE vs. CTS = 25.2; P<0.0001), while CTS did not provide any statistically significant information to SPARE (SPARE+CTS vs. SPARE = 2.1, P=0.14). Using predefined cut-offs to stratify chemo-naïve patients clinically estimated at low recurrence risk, SPARE identified low, intermediate and high risk patients based on their annual rate of DM in the early (low, 0.2%, intermediate, 0.8%, high, 3.3%) and late (low, 0.3%, intermediate, 0.9%, high, 1.6%) interval. Conclusions: SPARE represents a more refined clinical tool, compared to standard clinicopathological parameters, that could be used for personalized therapeutic decision making in ER+/HER2- BC patients.

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.

Sign in / Sign up

Export Citation Format

Share Document