scholarly journals Ki67 Assessment by qRT-PCR in OncotypeDx ® Breast Recurrent Score®: Low Correlation With IHC Assessment of ki67 and Prognostic Impact of ki67 RNA Level of Expression.

2021 ◽  
Author(s):  
Zohair Selmani ◽  
Chloé Molimard ◽  
Alexis Overs ◽  
Fernando Bazan ◽  
Loic Chaigneau ◽  
...  
Keyword(s):  
Early Stage ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Oncotype Dx ◽  
Expression Level ◽  
Prognostic Impact ◽  
Breast Cancers ◽  
Event Free Survival ◽  
Free Survival ◽  
Qrt Pcr

Abstract Background: Breast cancers expressing high levels of Ki67 are associated with poor outcomes. To provide individualized patient care, reliability of prognostic and predictive information deriving from Ki67 assessment is essential. Oncotype DX® test was designed for ER+/HER2- early-stage breast cancers to help adjuvant chemotherapy decision by providing a Recurrent Score® (RS®). RS® measures the expression of 21 specific genes from tumor tissue, including Ki67, and aim to predict the benefit of chemotherapy and the risk of distant recurrence. The primary aim of this study was to assess the agreement between Ki67RNA obtained with Oncotype DX® RS® and Ki67IHC. Other objectives were to analyze the association between the event free survival (EFS) and the expression level of Ki67RNA; and association between RS® and Ki67RNA.Methods: In a cohort of 98 patients with early ER+/HER2- breast cancers, we obtained: Recurrence score®, RNA level of Ki67 expression measured when assessing RS® and Ki67 tumor labelling by immunohistochemistry (Ki67IHC). The Ki67RNA was compared to the Ki67IHC by Kappa Cohen test. With a mean follow-up of 57 months, the association between the event free survival (EFS) and Ki67 status was measured using R package survival. Results: This population was essentially composed of no special type tumor (91%), N0 or Nmic (71%), grade 1 (62%), and tumor size pT1c (1-2 cm) (58%). The RS® values were <18 in 38% (n=37), 18-30 in 51% (n=50) and >30 in 11% (n=11) of the patients. A low agreement of 0.24 was found by Cohen’s kappa test between Ki67IHC and Ki67RNA. Moreover, Ki67RNAhigh tumors were significantly associated with the occurrence of events (p=0.02). On the other hand, we did not find any association between Ki67IHC and EFS (p=0.25).Conclusion: We observed of low agreement between expression level of Ki67RNA and Ki67 protein labelling by IHC. Unlike Ki67IHC and independently of the RS®, Ki67RNA could have a prognostic value. It would be interesting to better assess the prognosis and predictive value of Ki67RNA measured by qRT-PCR. The Ki67RNA in medical routine could be a good support in countries where Oncotype DX® is not accessible.

Ki67 Assessment By qRT-PCR In OncotypeDx® Breast Recurrent Score®: Low Correlation With Immunohistochemistry Assessment of Ki67 And Prognostic Impact of Ki67 RNA Level of Expression.

2021 ◽  
Author(s):  
Zohair Selmani ◽  
Chloé Molimard ◽  
Alexis Overs ◽  
Fernando Bazan ◽  
Loic Chaigneau ◽  
...  
Keyword(s):  
Early Stage ◽  
Oncotype Dx ◽  
Expression Level ◽  
Prognostic Impact ◽  
Breast Cancers ◽  
Free Survival ◽  
Qrt Pcr ◽  
Kappa Test ◽  
Poor Outcomes ◽  
Good Support

Abstract Breast cancers expressing high levels of Ki67 are associated with poor outcomes. Oncotype DX® test was designed for ER+/HER2- early-stage breast cancers to help adjuvant chemotherapy decision by providing a Recurrent Score® (RS®). RS® measures the expression of 21 specific genes from tumor tissue, including Ki67. The primary aim of this study was to assess the agreement between Ki67RNA obtained with Oncotype DX® RS® and Ki67IHC. Other objectives were to analyze the association between the event free survival (EFS) and the expression level of Ki67RNA; and association between RS® and Ki67RNA.Herein, we report a low agreement of 0.24 by Cohen’s kappa test between Ki67IHC and Ki67RNA in a cohort of 98 patients with early ER+/HER2- breast cancers. Moreover, Ki67RNAhigh tumors were significantly associated with the occurrence of events (p=0.02). On the other hand, we did not find any association between Ki67IHC and EFS (p=0.25).We observed of low agreement between expression level of Ki67RNA and Ki67 protein labelling by IHC. Unlike Ki67IHC and independently of the RS®, Ki67RNA could have a prognostic value. It would be interesting to better assess the prognosis and predictive value of Ki67RNA measured by qRT-PCR. The Ki67RNA in medical routine could be a good support in countries where Oncotype DX® is not accessible.

Simulation modeling of the effects of adjuvant chemotherapy in early-stage breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 526-526
Author(s):  
Jinani Jayasekera ◽  
Clyde B. Schechter ◽  
Joseph A. Sparano ◽  
Claudine Isaacs ◽  
Robert James Gray ◽  
...  
Keyword(s):  
Simulation Model ◽  
Simulation Modeling ◽  
Early Stage ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Recurrence Free Survival ◽  
Breast Cancers ◽  
Recent Trial ◽  
Free Survival ◽  
Cut Points

526 Background: The recent Trial Assigning Individualized Options for Treatment (TAILORx) was practice changing. However, several important questions remain unanswered about therapy for women with early stage, hormone receptor positive (HR+), HER2- breast cancers, including chemotherapy effects by age and different Oncotype recurrence score (RS) cut-points, and longer follow-up. We developed a simulation model to extend the trial results to begin to fill these gaps. Methods: We developed a simulation model using an empirical Bayesian approach to simulate women eligible for the TAILORx trial. The joint distributions of patient and tumor characteristics were derived from de-identified TAILORx data. The remaining inputs used data independent of the trial, including SEER, the Oxford Overview, and other trials. TAILORx was simulated to examine the effects of chemotherapy (+ hormonal Rx) vs. hormonal Rx alone on distant recurrence-free survival (DRFS) at 9- and 20-years by age (≤50 and >50 years) and RS (11-25 and 16-25). We also evaluated the effects of chemotherapy in women with RS 26-30. Hazard ratios (HR) were determined using Cox regressions and DRFS by treatment were derived from Kaplan-Meier curves. We report the mean results from 1000 trial simulations, where each simulation randomly sampled values for each parameter from their observed joint distribution. Finally, the original trial was replicated for model validation. Results: The model closely replicated actual trial results. Sample sizes ranged from 7000-10000. The model estimated that chemotherapy improved DFRS in women aged ≤50 with RS 16-25 (Table). The 20-year event rates remained low in the 11-25 category. Among women with RS 26-30, HR for no chemo vs. chemo was 1.38 (95% CI:1.18-1.58). Conclusions: Simulation suggests that chemotherapy may reduce distant recurrence in younger women at different cut points between 11-25. Simulation modeling may be useful to translate trial results to broader population subgroups than those possible to test in RCTs. Nine-year distant recurrence-free survival by chemotherapy. [Table: see text]

Abstract Submission

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 526-526 ◽  
Author(s):  
L. J. Goldstein ◽  
R. Gray ◽  
B. H. Childs ◽  
D. Watson ◽  
S. G. Rowley ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Recurrence Score ◽  
Recurrence Risk ◽  
Oncotype Dx ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Breast Cancers ◽  
Free Survival ◽  
Increased Risk

526 Background: Evidence suggests modern chemotherapy (CT) regimens are only marginally more effective in HR-pos breast cancer (Berry et al. JAMA 2006: 295: 1658). Genomic classifiers may be useful for selection of high-risk subjects for more aggressive CHT. Methods: A case-cohort sample of 776 patients enrolled on E2197 who did (N=179) or did not have a recurrence after CT (if HR-neg) or CHT (if HR-pos) and had available tissue were evaluated for Oncotype DX™ Recurrence Score (RS). E2197 included 2885 evaluable patients with 0–3 positive nodes treated with four 3-week cycles of doxorubicin (60 mg/m2) plus cyclophosphamide 600 mg/m2 (AC) or docetaxel 60 mg/m2 (AT) and hormonal therapy (if HR-pos). Median follow-up was 76 months. Results: There was no difference in DFS between treatment arms. In multivariate analysis, RS was a significant predictor of recurrence in HR-pos disease (p=0.0007, recurrence risk 21% lower for each 10 point drop in RS, 95% confidence intervals 9% to 31%). Recurrence risk was significantly elevated for an intermediate RS 18–30 (n=138, hazard ratio [HR] 2.96 [p=0.0002]) or a high RS ≥ 31 (n=108, HR 4.00, p=0.0001) compared with low RS < 18(n=196), but not for high compared with intermediate RS (HR 1.34, [p=0.32]); results were similar if only HER2-neg disease was included. The 5-year relapse free interval(RFI), breast cancer free survival (BCFS), disease-free survival (DFS), and overall survival (OS) for patients with HR-pos, HER2-neg disease are shown below (%); patients with both node-neg or node-pos breast cancers whose RS was < 18 had excellent outcomes. Conclusions: Oncotype DX™ RS identifies individuals with HR-pos, HER2-neg breast cancer with 0–3 positive axillary lymph nodes at 3–4-fold increased risk of relapse despite standard CHT, and may serve as a means to distinguish between those who do well with standard CHT (RS <18) from those who may be suitable candidates for clinical trials evaluating alternative CT regimens or other strategies (RS ≥ 18). [Table: see text] [Table: see text]

Is the Oncotype DX Assay Necessary in Strongly Estrogen Receptor-Positive Breast Cancers?

2011 ◽  
Vol 77 (10) ◽  
pp. 1364-1367 ◽  
Author(s):  
Jenny J. Lee ◽  
Jeannie Shen
Keyword(s):  
Estrogen Receptor ◽  
Clinical Utility ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
Good Prognosis ◽  
Oncotype Dx ◽  
Breast Cancers ◽  
Hospital Patients ◽  
Estrogen Receptor Positive ◽  
Er Positive

The 21-gene Oncotype DX recurrence score (RS) assay quantifies risk of distant recurrence and predicts benefit from chemotherapy in tamoxifen-treated estrogen receptor (ER)-positive, node-negative breast cancer. Although clinically useful, the assay costs roughly $4650. Because the assay is weighted heavily towards expression of ER, our objective was to determine its clinical utility in strongly ER-positive tumors. This was a retrospective study of Huntington Hospital patients undergoing an Oncotype DX assay between 2007 and 2010. Data collected included patient age, expression of ER, progesterone receptor (PR), HER2/neu, ki67, and p53, tumor size, node status, lymphovascular invasion, and nuclear grade. Of 133 total patients, 84 (63.2%) had strongly ER-positive tumors (≥90% expression). Only seven of 84 patients (8.3%) had a high risk RS (>30), indicating statistically significant predicted benefit from chemotherapy. All seven had intermediate to high ki67 expression (>20%) and lower PR expression (≤50%). Our study demonstrates that the clinical utility of the Oncotype DX assay in these patients is limited as most patients with strongly ER-positive tumors will have a low or intermediate RS. Future studies are needed to identify additional predictive factors in these patients with otherwise good prognosis.

Neuregulin Expression Modulates Clinical Response to Trastuzumab in Patients With Metastatic Breast Cancer

2007 ◽  
Vol 25 (19) ◽  
pp. 2656-2663 ◽  
Author(s):  
Enrique de Alava ◽  
Alberto Ocaña ◽  
Mar Abad ◽  
Juan Carlos Montero ◽  
Azucena Esparís-Ogando ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Early Stage ◽  
Metastatic Breast ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Event Free Survival ◽  
Mcf7 Cells ◽  
Free Survival ◽  
Her 2

Purpose Human epidermal growth factor receptor 2 (HER-2) overexpression has been associated with the genesis and progression of a subset of breast cancers. The function of HER-2 may be upregulated by overexpression or by the availability of neuregulins (NRGs), a group of transmembrane growth factors. Transmembrane NRGs strongly activated HER-2 and cell proliferation in breast cancer cells that did not overexpress HER-2, and treatment with trastuzumab prevented the proliferative action of transmembrane NRG. This raised the relevant clinical question of whether patients considered as HER-2 negative, but expressing transmembrane NRG, may benefit from treatment with trastuzumab. Patients and Methods MCF7 cells expressing transmembrane NRG (MCF7-NRGα2c) were injected into mice, and their sensitivity to trastuzumab was assessed. A retrospective study of 124 patients with early-stage or metastatic breast cancer was conducted. Expression of transmembrane NRG was evaluated by immunohistochemistry. In 11 patients, Western blot for NRGs was also carried out. Statistics were performed to analyze possible correlations between NRG expression and response to trastuzumab-based therapies, event-free survival, and overall survival (OS). Results Trastuzumab inhibited tumor growth in mice injected with MCF7-NRGα2c cells. Transmembrane NRG was frequently expressed in breast cancer patients. Overexpression of transmembrane NRG significantly correlated with a longer event-free survival and OS in patients with low or normal HER-2 expression who were treated with trastuzumab-based therapies but not in patients with HER-2 overexpression. Conclusion We suggest that the spectrum of patients who may benefit from trastuzumab-based therapies may be widened to include patients with metastatic breast cancer without HER-2 amplification but who express transmembrane NRGs.

Can high Ki67 predict distant recurrence in early-stage breast cancer with low Oncotype Dx score?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12561-e12561
Author(s):  
Parvaneh Fallah ◽  
Nasser Khleel Mulla ◽  
Raquel Aloyz ◽  
Olga Aleynikova ◽  
Anca Florea ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Risk Group ◽  
Early Stage ◽  
Recurrence Score ◽  
Distant Recurrence ◽  
High Risk Group ◽  
Low Risk ◽  
Oncotype Dx ◽  
Early Stage Breast Cancer

e12561 Background: Ki-67 is a marker of proliferating cells. The recurrence score based on the 21-gene breast cancer assay also called Oncotype Dx provides prognostic and predictive information for recurrence in early stage breast cancer patients. We previously showed that there is a moderate correlation between Ki67 and oncotype Dx recurrence score. In this retrospective study, we aimed to examine whether high Ki67 could predict the distant recurrence in early stage breast cancer with low oncotype Dx scores ( < 25). Methods: This retrospective study included 278 consecutive cases of hormone receptor-positive, HER2 negative (T1-2 N0 M0) breast cancer who were diagnosed between 2008 and 2015 with low oncotype Dx ( < 25). Patients’ clinical outcome in terms of distant recurrence after breast surgery was determined up to December 2020 (median follow-up of 7 years). Patients were divided in to low risk (Ki67 < 15%) and high risk (Ki67 > = 15%) groups. Results: Of 278 cases with average and median age of 59 and 60 respectively, 148 (53%) were in Ki67 low risk and 130 (47%) were in Ki67 high risk group. Average and median oncotype Dx were 13.86 and 15 respectively in Ki67 low risk versus 15.23 and 16 respectively in Ki67 high risk group. 13 patients (4%) experienced distant metastasis in lung, liver, bone and skin. Of these 13 cases with average and median oncotype Dx 15.84 and 19 respectively, 12 (92%) were in the Ki67 high risk group and only 1 (8%) belonged to the low risk category. High Ki67 patients were overrepresented in group with recurrent distant metastasis compare to group without recurrent disease (Pearson Chi-Square = 51.18 with 1 degree of freedom and P = < 0.001). Conclusions: Ki67 high patients in the low risk oncotype Dx group are relapsing at a significantly higher rate suggesting that Ki67 combined with low oncotype Dx further refines the risk of distant relapse.

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.

scholarly journals The ZNF217 Biomarker Predicts Low- and High-Risk Oncotype DX® Recurrence Score in ER-Positive Invasive Breast Cancers

2019 ◽  
Vol 10 ◽  
Author(s):  
Pascale A. Cohen ◽  
Olivier Loudig ◽  
Christina Liu ◽  
Joseph Albanese ◽  
Susan Fineberg
Keyword(s):  
High Risk ◽  
Recurrence Score ◽  
Oncotype Dx ◽  
Breast Cancers ◽  
Er Positive

scholarly journals Quantitative mRNA Expression Assays and Synchronous Breast Cancers: A Case Report

2019 ◽  
Vol 12 (2) ◽  
pp. 418-420
Author(s):  
Steven Sorscher
Keyword(s):  
Endocrine Therapy ◽  
Recurrence Risk ◽  
Distant Recurrence ◽  
Oncotype Dx ◽  
The Other ◽  
Precision Oncology ◽  
Breast Cancers ◽  
Rt Pcr ◽  
Mrna Analysis ◽  
Cancer Network

Quantitative mRNA analysis of breast tumors represents a routinely applied example of precision oncology. Currently the National Comprehensive Cancer Network (NCCN) recommends quantitative mRNA profiling (e.g., 21-gene RT PCR or Oncotype Dx assay) for nearly all surgically resected lymph node (LN) negative hormone receptor (HR) positive, HER2 negative breast cancers in order to predict recurrence risk with endocrine therapy compared to chemotherapy followed by endocrine therapy after surgery. The incidence of synchronous breast cancers is low and evidence concerning distant recurrence risk is limited, but the risk of distant recurrence from one or the other of two primary breast cancers appears to be higher than the recurrence risk of the single largest of the two cancers. In this report, a woman with synchronous primary breast cancers is described. Oncotype Dx testing was done on each of her two cancers. By assuming that the recurrence risk from each with adjuvant endocrine therapy is an independent event, the recurrence likelihood from one or the other or both is calculated. I propose that this calculated value more accurately should predict the recurrence from one or the other or both tumors with endocrine therapy or chemotherapy followed by endocrine therapy compared with using only the higher of the two Oncotype Dx estimated risks.

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