Impact of clinical risk category on prognosis and prediction of chemotherapy benefit in early breast cancer (EBC) by age and the 21-gene recurrence score (RS) in TAILORx.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 503-503
Author(s):  
Joseph A. Sparano ◽  
Robert James Gray ◽  
Della F. Makower ◽  
Tracy G. Lively ◽  
Thomas James Saphner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Risk Category ◽  
Low Grade ◽  
Prognostic Information ◽  
Clinical Risk ◽  
Prognosis And Prediction ◽  
High Clinical Risk ◽  
Clinical Trial Information

503 Background: TAILORx established that endocrine therapy (ET) alone is non-inferior to adjuvant chemotherapy (CT) plus ET in EBC and a 21-gene RS of 11-25, with some benefit if ≤50 years (y) with RS 16-25 (PMID: 29860917). We evaluated whether clinical risk (tumor size & histologic grade) provides additional prognostic information to RS, a secondary trial objective. Methods: Clinical risk by was assessed by Adjuvant! (version 8.0) using MINDACT criteria (PMID 27557300), defined as low clinical risk (LCR - tumor ≤3 cm and low grade, <2 cm and intermediate grade, or ≤1 cm and high grade) or high clinical risk (HCR -not meeting LCR criteria). Results: Of 9427 women with RS and clinical risk information, 70% were LCR and 30% HCR, with comparable distribution by age ( ≤50 vs. >50). The RS was 26-100 in 9% of LCR and 27% of HCR patients, with similar distributions by age. Although LCR/HCR provided additional prognostic information in each RS category for iDFS, including RS 0-10 (9-year rates 86.7% vs. 75.7% LCR vs. HCR), 11-25 (85.4% vs. 78.9%), and 26-100 (82.0% vs. 70.4%), iDFS rates were similar irrespective of CT (no vs. yes) in the entire RS 11-25 cohort whether LCR (85.8% vs. 85.1%) or HCR (79.8% vs. 77.9%). DRFI rates were also similar irrespective of CT in the RS 11-25 cohort or > 50y group whether LCR (96.0% vs. 96.1% overall; 96.5% vs. 96.0% > 50y) or HCR (92.3% vs. 89.9% overall; 91.7% vs. 90.7% >50y). For women ≤50y, the absolute reduction in distant recurrence from CT with a RS of 16-20 (N=923) was -0.2% (standard error [SE]±2.1%) for LCR vs. 6.5%(SE±4.9%) for HCR (vs. 1.6%[SE±1.9%] overall), whereas for a RS 21-25 (N=492) it was 6.4% (SE±4.9%) for LCR vs. 8.6% (SE±6.2%) for HCR (vs. 6.5%[SE±3.7%] overall). Conclusions: Clinical risk stratification provides additional prognostic information to the 21-gene RS, but not prediction of CT benefit in the overall TAILORx population or those > 50y, and facilitates more refined estimates of absolute CT benefit for women ≤50y with a RS 16-25. (Funded by National Cancer Institute, Komen Foundation, Breast Cancer Research Foundation). Clinical trial information: NCT00310180.

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.

Analysis of factors related to adjuvant chemotherapy decision in early breast cancer patients with intermediate recurrence score.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12032-e12032
Author(s):  
Feilin Qu ◽  
Jiayi Wu ◽  
Xiaosong Chen ◽  
Ou Huang ◽  
Jianrong He ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Predictive Factors ◽  
Molecular Subtype ◽  
Recurrence Score ◽  
Tumor Grade ◽  
Clinical Risk ◽  
Gene Assay ◽  
High Clinical Risk

e12032 Background: The 21-gene Recurrence Score (RS) assay has been routinely used to guide systemic chemotherapy in patients (pts) with estrogen receptor positive, node-negative early breast cancer (EBC). However, there has been less clarity in recommendation of adjuvant chemotherapy (ACT) in pts with intermediate RS (IRS). According to the definitions of IRS in retrospective NSABP B14, B20 trials and prospective validation of TAILORx trial, we adopted the broaden cut-offs of 11-30 in our study. We sought to analyze the factors related to ACT decision in this subset of pts. Additionally, the role of Adjuvant!Online (AOL) was evaluated in ACT decision. Methods: A cohort of 564 pts with RS of 11-30 was retrospectively analyzed from January 2014 to October 2016 in Ruijin Hospital Shanghai Jiaotong University School of Medicine. The Oncotype DX RS, a RT-PCR 21-gene assay, was performed on RNA extracted from formalin-fixed paraffin-embedded tissue. The AOL was used to determine pts’ clinical risk. Predictive factors of chemotherapy usage in different clinical risk catogories were also assessed. Results: 267 (47.3%) pts received chemotherapy. Age, tumor grade, pathologic type, pT, pN, molecular subtype and RS were significantly correlated with ACT decision ( p <0.05). These factors were all independent predictors of ACT usage ( p<0.05) in mutivariable model. AOL was successfully measured in 504 (89.4%) pts, of whom 279 (49.5%) were at low clinical risk and 225 (39.9%) had high clinical risk. The distribution of RS correlated significantly with AOL clinical risk catogories. The predictive factors of ACT administration in high and low clinical risk subgroups were highly consistent with the overall population, except pT in high clinical risk pts. Discordances between clinical risk and ACT decision were found in 158 pts (28.0%), probably due to different age, molecular subtype and RS. Conclusions: Age, tumor grade, pathologic type, pT, pN, molecular subtype and RS were independent predictors of ACT administration in EBC pts with IRS. AOL should not be used alone to aid chemotherapy decision in this subset of pts.

Outcome of patients with an ultralow risk 70-gene signature in the MINDACT trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 500-500
Author(s):  
Josephine Lopes Cardozo ◽  
Caroline Drukker ◽  
Marjanka Schmidt ◽  
Laura van 't Veer ◽  
Annuska Glas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cox Regression ◽  
Gene Signature ◽  
Distant Recurrence ◽  
Low Risk ◽  
Risk Category ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Clinical Risk ◽  
Risk Patients

500 Background: Gene signatures have proven successful in identifying patients with a low risk of distant recurrence who could forego chemotherapy (CT) and are currently included in international treatment guidelines for breast cancer. For the 70-gene signature (MammaPrint) an additional threshold was established within the low risk category to identify patients with an ultralow risk of distant recurrence. In independent cohorts, these patients had excellent breast cancer specific survival at 15 years, suggesting that ultralow risk cancers represent indolent disease (Esserman, JAMA Oncol 2017, Delahaye, BC Res Treat 2017). Here we evaluate survival of patients with an ultralow risk 70-gene signature who participated in the randomized phase 3 MINDACT trial (Piccart, Lancet Oncol 2021). Methods: Of the 6,693 patients enrolled in the MINDACT trial (EORTC 10041/BIG 3-04) between 2007-2011, profiling revealed an ultralow risk 70-gene signature in 1,000 patients (15%). We assessed 5- and 8-year distant metastasis free interval (DMFI) and breast cancer specific survival (BCSS) in patients stratified by 70-gene signature result (high, low, ultralow), and within the ultralow risk group stratified by clinical risk. For these exploratory analyses, we used Kaplan-Meier estimates for time to event endpoints and Cox-regression models to calculate hazard ratio’s (HR). Results: Median follow-up was 8.7 years. Among the ultralow risk patients (n = 1,000), 67% were ≥50 years, 81% had tumors < 2cm, 80% were lymph node negative, 96% had grade 1 or 2 tumors and 99% were ER-positive. Systemic therapy was received by 83% of patients (69% endocrine therapy (ET), 14% ET + CT) and 16% received no adjuvant systemic treatment (AST). Survival estimates for all endpoints are shown in the table; 8-year DMFI was 97.0% (95% CI 95.8-98.1) for ultralow risk. The 8-year DMFI in ultralow risk patients who received no AST or ET only was 97.8% (95% CI 95.3-100) and 97.4% (95% CI 96.1-98.7), respectively. The HR for DMFI was 0.66 (95% CI 0.46-0.95) for ultralow vs low risk, after adjusting for tumor and treatment characteristics (preliminary results). Conclusions: In this prospective study, patients with an ultralow risk 70-gene signature have an excellent prognosis with 8-year BCSS above 99% regardless of clinical risk status, and with an 8-year DMFI of 95-98%.[Table: see text]

Prognostic Value of a Combined Estrogen Receptor, Progesterone Receptor, Ki-67, and Human Epidermal Growth Factor Receptor 2 Immunohistochemical Score and Comparison With the Genomic Health Recurrence Score in Early Breast Cancer

2011 ◽  
Vol 29 (32) ◽  
pp. 4273-4278 ◽  
Author(s):  
Jack Cuzick ◽  
Mitch Dowsett ◽  
Silvia Pineda ◽  
Christopher Wale ◽  
Janine Salter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Value ◽  
Growth Factor Receptor ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Prognostic Information ◽  
Ki 67 ◽  
Epidermal Growth ◽  
Separate Cohort ◽  
Ihc Markers

Purpose We recently reported that the mRNA-based, 21-gene Genomic Health recurrence score (GHI-RS) provided additional prognostic information regarding distant recurrence beyond that obtained from classical clinicopathologic factors (age, nodal status, tumor size, grade, endocrine treatment) in women with early breast cancer, confirming earlier reports. The aim of this article is to determine how much of this information is contained in standard immunohistochemical (IHC) markers. Patients and Methods The primary cohort comprised 1,125 estrogen receptor–positive (ER-positive) patients from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial who did not receive adjuvant chemotherapy, had the GHI-RS computed, and had adequate tissue for the four IHC measurements: ER, progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), and Ki-67. Distant recurrence was the primary end point, and proportional hazards models were used with sample splitting to control for overfitting. A prognostic model that used classical variables and the four IHC markers (IHC4 score) was created and assessed in a separate cohort of 786 patients. Results All four IHC markers provided independent prognostic information in the presence of classical variables. In sample-splitting analyses, the information in the IHC4 score was found to be similar to that in the GHI-RS, and little additional prognostic value was seen in the combined use of both scores. The prognostic value of the IHC4 score was further validated in the second separate cohort. Conclusion This study suggests that the amount of prognostic information contained in four widely performed IHC assays is similar to that in the GHI-RS. Additional studies are needed to determine the general applicability of the IHC4 score.

scholarly journals Optimizing the Use of Gene Expression Profiling in Early-Stage Breast Cancer

2016 ◽  
Vol 34 (36) ◽  
pp. 4390-4397 ◽  
Author(s):  
Hyun-seok Kim ◽  
Christopher B. Umbricht ◽  
Peter B. Illei ◽  
Ashley Cimino-Mathews ◽  
Soonweng Cho ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Decision Making ◽  
Gene Expression Profiling ◽  
Expression Profiling ◽  
Early Stage ◽  
Recurrence Score ◽  
Clinical Samples ◽  
Risk Category ◽  
Clinical Risk

Purpose Gene expression profiling assays are frequently used to guide adjuvant chemotherapy decisions in hormone receptor–positive, lymph node–negative breast cancer. We hypothesized that the clinical value of these new tools would be more fully realized when appropriately integrated with high-quality clinicopathologic data. Hence, we developed a model that uses routine pathologic parameters to estimate Oncotype DX recurrence score (ODX RS) and independently tested its ability to predict ODX RS in clinical samples. Patients and Methods We retrospectively reviewed ordered ODX RS and pathology reports from five institutions (n = 1,113) between 2006 and 2013. We used locally performed histopathologic markers (estrogen receptor, progesterone receptor, Ki-67, human epidermal growth factor receptor 2, and Elston grade) to develop models that predict RS-based risk categories. Ordering patterns at one site were evaluated under an integrated decision-making model incorporating clinical treatment guidelines, immunohistochemistry markers, and ODX. Final locked models were independently tested (n = 472). Results Distribution of RS was similar across sites and to reported clinical practice experience and stable over time. Histopathologic markers alone determined risk category with > 95% confidence in > 55% (616 of 1,113) of cases. Application of the integrated decision model to one site indicated that the frequency of testing would not have changed overall, although ordering patterns would have changed substantially with less testing of estimated clinical risk–high or clinical risk–low cases and more testing of clinical risk–intermediate cases. In the validation set, the model correctly predicted risk category in 52.5% (248 of 472). Conclusion The proposed model accurately predicts high- and low-risk RS categories (> 25 or ≤ 25) in a majority of cases. Integrating histopathologic and molecular information into the decision-making process allows refocusing the use of new molecular tools to cases with uncertain risk.

Prospective WSG phase III PlanB trial: Final analysis of adjuvant 4xEC→4x doc vs. 6x docetaxel/cyclophosphamide in patients with high clinical risk and intermediate-to-high genomic risk HER2-negative, early breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 504-504 ◽  
Author(s):  
Nadia Harbeck ◽  
Oleg Gluz ◽  
Michael R. Clemens ◽  
Wolfram Malter ◽  
Toralf Reimer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Breast Cancer ◽  
Triple Negative ◽  
Recurrence Score ◽  
Final Analysis ◽  
Clinical Risk ◽  
Central Pathology ◽  
High Clinical Risk

504 Background: Optimal chemotherapy in HER2-negative, particularly HR-positive, early breast cancer (EBC), especially the survival impact of anthracyclines, is still a matter of debate. Retrospective analyses saw most benefit of 6xCEF vs. 6xCMF in HER2+ EBC. Prospective trials have shown conflicting results; no predictive molecular factors have been validated so far, particularly for HR+ EBC. The WSG PlanB trial is the first trial that randomized only patients with high clinical risk or with Recurrence Score >11 in the HR+/HER2- subgroup (pN0-1). Patients with RS<11 (pN0-1) had an excellent prognosis (five-year DFS of 94%) with endocrine therapy alone (Gluz et al. ASCO 2016). Methods: The WSG PlanB trial was originally planned as a non-inferiority study for comparison of 6 cycles of anthracycline-free TC (Arm A) vs. standard anthracycline-taxane based chemotherapy (4xEC→4xDoc) (Arm B) in patients with high-risk pN0 (T2-4, G2-3, <35 years, or high uPA/PAI-1) or pN+ HER2- EBC. Following an early amendment, Oncotype DX was performed in all HR+ tumors, and omission of chemotherapy (CT) was recommended in RS≤11 HR+ pN0-1 disease. Primary endpoint was DFS, defined as time to any recurrence, secondary cancer or death. Final analysis for the CT randomization was planned after completed 5-year follow-up in all patients. Results: From 2009 to 2011, PlanB enrolled 3198 patients (n=3073 with central pathology review). In 348 patients (15.3%), CT was omitted based on RS≤11. 2449 patients were randomized to 6xTC (n=1222) and 4xEC→4xDoc (n=1227). Within this cohort, 41% were pN+, 42% had G3 tumors and 18% HR-negative tumors by central pathology. After median follow-up of 61 months, very similar five-year DFS of 89.9% [88.1%-91.7%] vs. 90.2% [88.4%-92.0%] and five-year OS of 94.7% [93.4%-96.1%] vs. 94.6% [93.2%-96.0%] were observed in Arms A vs. B. Five treatment-related deaths were observed in Arm A (TC) vs. one in Arm B (EC-Doc) (0.4% vs. 0.1%), despite a trend to more SAE’s in Arm B vs. Arm A (n=397 vs. 358). Although recurrence score is a strong prognostic factor, it was not predictive for anthracycline efficacy; no efficacy differences between the study arms were observed in (locally) triple-negative patients or in those with >4 involved lymph nodes, despite the prognostic impact of these factors. Conclusion: In the WSG PlanB trial, patients with early HER2-negative BC seem to be sufficiently treated by six cycles of docetaxel/cyclophosphamide compared to four cycles of EC followed by four cycles of docetaxel -- no efficacy differences are evident in high-risk subgroups defined by triple-negative status, nodal status, or high Recurrence Score. Further prospective studies are urgently needed before final conclusions for impact of anthracyclines in HER2-negative BC can be drawn. Clinical trial information: NCT01049425.

scholarly journals Application of the 21-Gene Recurrence Score in Patients with Early HR-Positive/HER2-Negative Breast Cancer: Chemotherapy and Survival Rate According to Clinical Risk

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4003
Author(s):  
Soong June Bae ◽  
Sung Gwe Ahn ◽  
Jung Hwan Ji ◽  
Chihhao Chu ◽  
Dooreh Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Group ◽  
Recurrence Score ◽  
Rank Test ◽  
Breast Cancer Chemotherapy ◽  
Clinical Risk ◽  
Her2 Breast Cancer ◽  
Significant Difference ◽  
High Clinical Risk ◽  
The Impact

We assessed the impact of 21-gene Recurrence Score (RS) assay on chemotherapy decision-making according to binary clinical risk stratification in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. We included patients with tumors measuring 1–5 cm, N0-1, and HR+/HER2- breast cancer who underwent surgery followed by adjuvant treatment. The clinical risk was determined by a modified version of Adjuvant! Online. We performed propensity score matching (PSM) according to the application of 21-gene RS separately in the low and high clinical risk groups. Before PSM, 342 (39.0%) of 878 patients were classified as having high clinical risk. In the high clinical risk group, 21-gene RS showed a significantly reduced chemotherapy rate of 39.3%, without increasing the recurrence. After PSM, the 21-gene RS application significantly reduced chemotherapy rate by 34.0% in 200 patients with high clinical risk (21-gene RS application, 32.0% vs. no 21-gene RS application, 66.0%, p < 0.001). There was also no significant difference in RFS according to 21-gene RS status in the high clinical risk group (log-rank test, p = 0.467). These results support the usefulness of the 21-gene RS to reduce the chemotherapy rate without adversely affecting prognosis in a high clinical risk group.

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.

Sign in / Sign up

Export Citation Format

Share Document