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 Immune microenvironment and intrinsic subtyping in hormone receptor-positive/HER2-negative breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Gaia Griguolo ◽  
Maria Vittoria Dieci ◽  
Laia Paré ◽  
Federica Miglietta ◽  
Daniele Giulio Generali ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Gene Expression Data ◽  
Hormone Receptor ◽  
Tumor Biology ◽  
Expression Data ◽  
Immune Microenvironment ◽  
Immune Infiltrate ◽  
Hormone Receptor Positive ◽  
Her2 Breast Cancer

AbstractLittle is known regarding the interaction between immune microenvironment and tumor biology in hormone receptor (HR)+/HER2− breast cancer (BC). We here assess pretreatment gene-expression data from 66 HR+/HER2− early BCs from the LETLOB trial and show that non-luminal tumors (HER2-enriched, Basal-like) present higher tumor-infiltrating lymphocyte levels than luminal tumors. Moreover, significant differences in immune infiltrate composition, assessed by CIBERSORT, were observed: non-luminal tumors showed a more proinflammatory antitumor immune infiltrate composition than luminal ones.

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]

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.

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