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]

Estrogen receptor alpha (ESR1) gene amplification status and clinical outcome in tamoxifen-treated postmenopausal patients with endocrine-responsive early breast cancer: An analysis of the prospective ABCSG-6 trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10501-10501 ◽  
Author(s):  
Christian F. Singer ◽  
Frederik Holst ◽  
Stefan Steurer ◽  
E C Burandt ◽  
Hellmut Samonigg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Clinical Outcome ◽  
Copy Number ◽  
Estrogen Receptor Alpha ◽  
Distant Recurrence ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival ◽  
Esr1 Gene

10501 Background: Estrogen receptor alpha (ERα) expression is a prognostic parameter in breast cancer and predicts response to endocrine therapy. One of the factors important for protein expression is amplification of its encoding gene ESR1. We have investigated the value of ESR1 amplification in predicting the long-term clinical outcome in tamoxifen-treated postmenopausal women with endocrine-responsive breast cancer. Methods: 394 patients who had been randomized into the tamoxifen-only arm of the prospectively designed endocrine ABCSG-06 trial and in whom FFPE tumor tissue was available were included in this analysis. Immunohistochemical ERα expression was evaluated both locally and centrally using the Allred score, while ESR1 gene amplification status was evaluated by FISH analysis using the ESR1/CEN6 ratio. Results: ESR1 copy number gains were detected in 187 of 394 (47%) tumor specimen and was associated with favorable clinical outcome. At a median follow-up of 10 years, women with intratumoral ESR1 copy number gains had a significantly longer distant recurrence-free survival (adjusted HR for relapse 0.48; 95% CI 0.28-0.83; p=0.009) and breast cancer-specific survival (adjusted HR for death 0.46; CI 0.46-0.71; p=0.006) when compared to women with normal ESR1 copy numbers. Immunohistochemical ERα protein expression, evaluated by Allred score, was significantly correlated with ESR1 copy number alterations (p<0.0001; Chi-Square test), but did itself not allow to discriminate between patients with poor and good prognosis. Conclusions: ESR1 amplification status is an independent and powerful predictor for long-term distant recurrence-free and breast cancer-specific survival in postmenopausal women with endocrine-responsive early-stage breast cancer who received 5 years of tamoxifen.

scholarly journals The Landscape of Glycosyltransferase Gene Signature for Overall Survival Prediction in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Qiang Cai ◽  
Shizhe Yu ◽  
Jian Zhao ◽  
Duo Ma ◽  
Long Jiang ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Risk Score ◽  
Prognostic Value ◽  
Cox Regression ◽  
Risk Groups ◽  
Gene Signature ◽  
Low Risk ◽  
Regression Analyses ◽  
Risk Patients

Abstract Background: Hepatocellular carcinoma (HCC) is heterogeneous disease occurring in the background of chronic liver diseases. The role of glycosyltransferase (GT) genes have recently been the focus of research associating with the development of tumors. However, the prognostic value of GT genes in HCC remains not elucidated. This study aimed to demonstrate the GT genes related to the prognosis of HCC through bioinformatics analysis.Methods: The GT genes signatures were identified from the training set of The Cancer Genome Atlas (TCGA) dataset using univariate and the least absolute shrinkage and selection operator (LASSO) Cox regression analyses. Then, we analyzed the prognostic value of GT genes signatures related to the overall survival (OS) of HCC patients. A prognostic model was constructed, and the risk score of each patient was calculated as formula, which divided HCC patients into high- and low-risk groups. Kaplan-Meier (K-M) and Receiver operating characteristic (ROC) curves were used to assess the OS of HCC patients. The prognostic value of GT genes signatures was further investigated in the validation set of TCGA database. Univariate and multivariate Cox regression analyses were performed to demonstrate the independent factors on OS. Finally, we utilized the gene set enrichment analysis (GSEA) to annotate the function of these genes between the two risk categories. Results: In this study, we identified and validated 4 GT genes as the prognostic signatures. The K-M analysis showed that the survival rate of the high-risk patients was significantly lower than that of the low-risk patients. The risk score calculated with 4 gene signatures could predict OS for 3-, 5-, and 7-year in patients with HCC, revealing the prognostic ability of these gene signature. In addition, Multivariate Cox regression analyses indicated that the risk score was an independent prognostic factor for HCC. Functional analysis further revealed that immune-related pathways were enriched, and immune status in HCC were different between the two risk groups.Conclusion: In conclusion, a novel GT genes signature can be used for prognostic prediction in HCC. Thus, targeting GT genes may be a therapeutic alternative for HCC.

scholarly journals Identification of a Novel Glycolysis-Related Signature to Predict the Prognosis of Patients with Breast Cancer

2021 ◽  
Author(s):  
Menglin He ◽  
Cheng Hu ◽  
Jian Deng ◽  
Hui Ji ◽  
Weiqian Tian
Keyword(s):  
Breast Cancer ◽  
Risk Score ◽  
Cox Regression ◽  
Risk Group ◽  
Gene Signature ◽  
High Risk Group ◽  
Low Risk ◽  
Cox Regression Analysis ◽  
Expression Levels ◽  
Incidence And Mortality

Abstract Background: Breast cancer (BC) is a kind of cancer with high incidence and mortality in female. Conventional clinical characteristics are far from accurate to predict individual outcomes. Therefore, we aimed to develop a novel signature to predict the survival of patients with BC. Methods: We analyzed the data of a training cohort from the TCGA database and a validation cohort from GEO database. After the applications of GSEA and Cox regression analyses, a glycolysis-related signature for predicting the survival of patients with BC was developed. The signature contains AK3, CACNA1H, IL13RA1, NUP43, PGK1, and SDC1. Then, we constructed a risk score formula to classify the patients into high and low-risk groups based on the expression levels of six-gene in patients. The receiver operating characteristic (ROC) curve and the Kaplan-Meier curve were used to assess the predicted capacity of the model. Next, a nomogram was developed to predict the outcomes of patients with risk score and clinical features in 1, 3, and 5 years. We further used Human Protein Atlas (HPA) database to validate the expressions of the six biomarkers in tumor and sample tissues.Results: We constructed a six-gene signature to predict the outcomes of patients with BC. The patients in high-risk group showed poor prognosis than that in low-risk group. The AUC values were 0.719 and 0.702, showing that the prediction performance of the signature is acceptable. Additionally, Cox regression analysis revealed that these biomarkers could independently predict the prognosis of BC patients without being affected by clinical factors. The expression levels of all six biomarkers in BC tissues were higher than that in normal tissues except AK3. Conclusion: We developed a six-gene signature to predict the prognosis of patients with BC. Our signature has been proved to have the ability to make an accurate and obvious prediction and might be used to expand the prediction methods in clinical.

scholarly journals Independent Validation of EarlyR Gene Signature in BIG 1-98: A Randomized, Double-Blind, Phase III Trial Comparing Letrozole and Tamoxifen as Adjuvant Endocrine Therapy for Postmenopausal Women With Hormone Receptor–Positive, Early Breast Cancer

2019 ◽  
Vol 3 (4) ◽  
Author(s):  
Steven A Buechler ◽  
Kathryn P Gray ◽  
Yesim Gökmen-Polar ◽  
Scooter Willis ◽  
Beat Thürlimann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Confidence Interval ◽  
Gene Signature ◽  
Distant Recurrence ◽  
Free Interval ◽  
Formalin Fixed Paraffin ◽  
Formalin Fixed Paraffin Embedded ◽  
Risk Patients ◽  
Formalin Fixed

Abstract Background EarlyR gene signature in estrogen receptor–positive (ER+) breast cancer is computed from the expression values of ESPL1, SPAG5, MKI67, PLK1, and PGR. EarlyR has been validated in multiple cohorts profiled using microarrays. This study sought to verify the prognostic features of EarlyR in a case-cohort sample from BIG 1–98, a randomized clinical trial of ER+ postmenopausal breast cancer patients treated with adjuvant endocrine therapy (letrozole or tamoxifen). Methods Expression of EarlyR gene signature was estimated by Illumina cDNA-mediated Annealing, Selection, and Ligation assay of RNA from formalin-fixed, paraffin-embedded primary breast cancer tissues in a case-cohort subset of ER+ women (N = 1174; 216 cases of recurrence within 8 years) from BIG 1–98. EarlyR score and prespecified risk strata (≤25 = low, 26–75 = intermediate, &gt;75 = high) were “blindly” computed. Analysis endpoints included distant recurrence–free interval and breast cancer–free interval at 8 years after randomization. Hazard ratios (HRs) and test statistics were estimated with weighted analysis methods. Results The distribution of the EarlyR risk groups was 67% low, 19% intermediate, and 14% high risk in this ER+ cohort. EarlyR was prognostic for distant recurrence–free interval; EarlyR high-risk patients had statistically increased risk of distant recurrence within 8 years (HR = 1.73, 95% confidence interval = 1.14 to 2.64) compared with EarlyR low-risk patients. EarlyR was also prognostic of breast cancer–free interval (HR = 1.74, 95% confidence interval = 1.21 to 2.62). Conclusions This study confirmed the prognostic significance of EarlyR using RNA from formalin-fixed, paraffin-embedded tissues from a case-cohort sample of BIG 1–98. EarlyR identifies a set of high-risk patients with relatively poor prognosis who may be considered for additional treatment. Further studies will focus on analyzing the predictive value of EarlyR signature.

Breast cancer-specific survival outcomes among patients based on 21-gene recurrence score.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 537-537
Author(s):  
Wade T. Swenson ◽  
Shantanu Mallick
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Lobular Carcinoma ◽  
Survival Rates ◽  
Recurrence Score ◽  
Population Based ◽  
Low Risk ◽  
Intermediate Risk ◽  
Breast Cancer Specific Survival ◽  
Cancer Specific Survival

537 Background: The 21-gene recurrence assay predicts cancer recurrence rates and benefit from adjuvant chemotherapy among patients with hormone-receptor-positive breast cancer. The National Cancer Institute and Genomic Health collaborated to provide Recurrence Score (RS) results to complement data from 17 population-based cancer registries in the Surveillance, Epidemiology, and End Results (SEER) Program. Methods: Using the SEER database with linked RS results, a cohort of female breast cancer patients, age greater than 20 years, was identified by RS (low: < 18, intermediate: 18-30, high: > 30) diagnosed between the years 2004 and 2007. A retrospective analysis was conducted to determine eight-year breast cancer-specific survival rates based on RS and other variables. Results: 10,318 patients were identified in the cohort. 5,194 had a low risk RS; 4,282 had an intermediate risk RS; 872 had a high risk RS. Histologic subtypes were: 7,459 infiltrating ductal carcinoma, 941 mixed infiltrating and lobular carcinoma, 933 lobular carcinoma, 327 mixed infiltrating ductal and other histology, 244 mucinous adenocarcinoma, 101 tubular adenocarcinoma, 45 mixed lobular and other histology, 268 other histologies. 644 low risk RS patients received chemotherapy (12.4%); 1,608 intermediate risk RS patients received chemotherapy (37.8%); 593 high risk patients received chemotherapy (68.0%). The eight-year breast cancer-specific survival rates (with 95% confidence intervals) among low risk RS patients without known chemotherapy administration was 98.9% (98.5, 99.2), and 98.4% (97.0, 99.1) with chemotherapy; intermediate risk RS patients without known chemotherapy was 97.0% (96.2, 97.6), and 96.9% (95.9, 97.7) with chemotherapy; high risk RS patients without known chemotherapy was 89.7% (85.4, 92.8), and 92.9% (90.4, 94.7) with chemotherapy. Conclusions: Among a large cohort of patients identified in a population-based cancer registry between 2004 and 2007, there was no statistically significant difference in eight-year breast cancer-specific survival rates among those who received chemotherapy and those who did not, regardless of RS risk group.

Prognostic value of PD-L1 gene expression with Recurrence Score and 70-gene signature in patients with ER+/HER2- early breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 550-550
Author(s):  
Ioannis Zerdes ◽  
Emmanouil G. Sifakis ◽  
Nicholas Tobin ◽  
Jonas C. S. Bergh ◽  
Alexios Matikas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Mrna Expression ◽  
Prognostic Value ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Recurrence Score ◽  
Gene Signature ◽  
Cancer Specific Survival ◽  
Region Gene

550 Background: We have previously demonstrated that PD-L1 mRNA expression can serve as prognostic biomarker in breast cancer (BC). In ER+/HER2- BC, RS and 70-gene signature are used to predict the risk of recurrence and benefit from chemotherapy. Methods: Discovery cohort (cohort 1) included 302 patients diagnosed with primary ER+/HER2- BC (1997-2005) in Stockholm health care region. Gene expression profiling has been performed using DNA microarrays (GSE48091) while information regarding tumor characteristics, treatment and follow-up have been obtained. TCGA’s dataset including 590 ER+/HER2- patients, was used as validation cohort (cohort 2). Kaplan–Meier estimates and Cox regression univariate/multivariable analyses were performed using breast cancer-specific survival(BCSS) and progression-free interval (PFI) as endpoints in cohorts 1 and 2, respectively. Gene signature scores were calculated using the R genefu package. Likelihood ratio (LR) tests and concordance indices (c-indices) were used to assess each score’s added prognostic value. Results: PD-L1 mRNA expression (treated as a continuous variable) was independently associated with better BCSS in cohort 1 (HR = 0.72; 95% CI = 0.58-0.90;p = 0.003) and with better PFI in cohort 2 (HR = 0.67; 95% CI = 0.50-0.90; p = 0.008) in the multivariable analysis. PD-L1 provided significant additional prognostic information beyond that of both RS alone (LR-Δχ2= 9.6; p = 0.002 and LR-Δχ2= 9.7; p = 0.002, in cohorts 1 and 2, respectively), and 70-gene signature score alone (LR-Δχ2= 10.4; p = 0.001 and LR-Δχ2= 9.2; p = 0.002 in cohort 1 and 2, respectively). C-indices for PD-L1 + RS vs RS were 0.65 vs 0.60 (cohort 1) and 0.66 vs 0.60 (cohort 2), and for PD-L1 + 70-gene vs 70-gene were 0.65 vs 0.59 (cohort 1) and 0.64 vs 0.54 (cohort 2), respectively. Conclusions: PD-L1 gene expression was correlated with better outcomes and can provide added prognostic value to RS and 70-gene signature scores in ER+/HER2- BC.

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.

scholarly journals The beneficial role of Asian-based RecurIndex test in the prognostic prediction in Chinese male breast cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shuo Zhang ◽  
Beichen Liu ◽  
Mengli Zhou ◽  
Jintian Wang ◽  
Jinzhao Liu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Local Recurrence ◽  
Male Breast Cancer ◽  
Distant Recurrence ◽  
Low Risk ◽  
Free Survival ◽  
High Risk Patients ◽  
Risk Patients ◽  
N Stage

AbstractRecurIndex, a multigene profiling assay, can predict the risk of local recurrence and distant metastasis in female breast cancer (FBC), but its role in male breast cancer (MBC) remains unclear. In this study, the clinicopathological data of 43 consecutive MBC patients undergoing surgeries between 2009 and 2018 were retrospectively analysed. Their paraffin-embedded tissue sections were examined by RecurIndex test which comprised 2 models: recurrence index for local recurrence (RI-LR) and recurrence index for distant recurrence (RI-DR). Of 43 patients, there were 26 low-risk and 17 high-risk patients assessed by RI-LR, while 17 low-risk and 26 high-risk patients by RI-DR. For RI-LR, tumor N stage showed statistically significant (P < 0.001) between low- and high-risk patients; for RI-DR, differences were pronounced in tumor grade (P = 0.033), T stage (P = 0.043) and N stage (P = 0.003). In terms of clinical outcomes, the overall survival (OS) of low- and high-risk patients stratified by RI-LR showed no statistically significant differences (P = 0.460), while high-risk patients identified by RI-DR had a significantly worse distant recurrence-free survival (DRFS) (P = 0.035), progression-free survival (PFS) (P = 0.019) and OS (P = 0.044) than low-risk patients. Overall, RI-DR can effectively predict the DRFS, PFS and OS of MBC patients and identify those at low risk of recurrence, which may serve as a potential prognostic tool for MBC.

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