P01. Can one-step nucleic acid amplification assay predict 4 or more positive axillary lymph node involvement in breast cancer patients: A single centre retrospective study

Kenny, Ross; Sotheran, Wendy; Gould, Leila

doi:10.1016/j.ejso.2021.03.005

Cited by 3 publications

(6 citation statements)

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“…Lastly, for the subsequent multiple regression analysis (with each DEG as dependent variable and the respective signi cant clinicopathologic parameters as independent variables), as TTL and OSNA sample result were almost coincident (r s = 0.997; p < 0.001) (Additional le 2) and TTL have a greater and proven clinical relevance, only TTL was considered. (13,15,19) For KRT7, VTCN1, CD44, GATA3, ALOX15B and RORC, a multiple linear regression with normalized expression levels of each DEG as dependent variable and signi cant clinicopathologic parameters (Table 8) as independent variables was attempted, but none of the independent variables were statistically signi cant. However, multiple linear regression with normalized expression levels of NECTIN2, LRG1, CD276, FOXM1 and IGF1R as dependent variables and the corresponding signi cant clinicopathologic parameters (Table 8) as independent variables revealed: an independent linear relationship between TTL and normalized expression levels of NECTIN2 (b = 0.002; p < 0.001; R 2 = 0.791); an independent linear relationship between TTL and normalized expression levels of LRG1 (b = 0.002; p = 0.004; R 2 = 0.578); an independent linear relationship between TTL and normalized expression levels of CD276 (b = 0.001; p = 0.003; R 2 = 0.652); an independent linear relationship between TTL and normalized expression levels of FOXM1 (b = 0.001; p = 0.003; R 2 = 0.822); and an independent linear relationship between TTL and normalized expression levels of IGF1R (b = 0.012; p < 0.001; R 2 = 0.830).…”

Section: Statistical Analysis Between Degs and Relevant Clinicopathol...mentioning

confidence: 99%

“…(15,18) Previous studies revealed that TTL is an independent predictor of the status of the non-sentinel LNs in BC patients and to be independently correlated with disease free survival, local recurrence free survival and overall survival. (13,15,(18)(19)(20) Nevertheless, the exact TTL cut-off to determine ALND is still under debate. (13,18,19,21,22) Although LNs metastases is among the strongest predictors of prognosis, few studies have focused on the assessment of immunoin ammatory response in the LNs and the mechanisms that underlie the local failure of effective anti-tumor immune responses remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…(13,15,(18)(19)(20) Nevertheless, the exact TTL cut-off to determine ALND is still under debate. (13,18,19,21,22) Although LNs metastases is among the strongest predictors of prognosis, few studies have focused on the assessment of immunoin ammatory response in the LNs and the mechanisms that underlie the local failure of effective anti-tumor immune responses remain poorly understood. In LNs, exposure to tumor-derived factors induces stromal reprogramming, modi es immune cell population dynamics and affects chemokines and interleukins levels, which have the potential to contribute to impaired immune system response.…”

Section: Introductionmentioning

confidence: 99%

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Exploring the lymph node’s microenvironment for personalized management of luminal A breast cancer

Gante

Ribeiro²,

Gomes³

et al. 2022

European Journal of Cancer

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Section: Statistical Analysis Between Degs and Relevant Clinicopathol...mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exploring the lymph node’s microenvironment for personalized management of luminal A breast cancer

Gante

Ribeiro²,

Gomes³

et al. 2022

European Journal of Cancer

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“…Total tumor load (TTL) was defined as the sum of the total number of CK19 mRNA copies in all positive SLNs (in copies/μL) [ 15 , 18 ]. Previous studies revealed that TTL is an independent predictor of the status of the non-sentinel LNs in BC patients and to be independently correlated with disease free survival, local recurrence free survival and overall survival [ 13 , 15 , 18 , 19 , 20 ]. Nevertheless, the exact TTL cut-off to determine ALND is still under debate [ 13 , 18 , 19 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies revealed that TTL is an independent predictor of the status of the non-sentinel LNs in BC patients and to be independently correlated with disease free survival, local recurrence free survival and overall survival [ 13 , 15 , 18 , 19 , 20 ]. Nevertheless, the exact TTL cut-off to determine ALND is still under debate [ 13 , 18 , 19 , 21 , 22 ]. Moreover, despite all the benefits of the OSNA, one downside of the OSNA assay is the destruction of the SLNs, preventing further microstructural studies that could provide useful information on immune response and tumor aggressiveness.…”

Section: Introductionmentioning

confidence: 99%

One Step Nucleic Acid Amplification (OSNA) Lysate Samples Are Suitable to Establish a Transcriptional Metastatic Signature in Patients with Early Stage Hormone Receptors-Positive Breast Cancer

Gante

Ribeiro

Mendes

et al. 2022

Cancers

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The One Step Nucleic Acid Amplification (OSNA) is being adopted worldwide for sentinel lymph nodes (SLNs) staging in breast cancer (BC). As major disadvantage, OSNA precludes prognostic information based on structural evaluation of SLNs. Our aim is to identify biomarkers related to tumor-microenvironment interplay exploring gene expression data from the OSNA remaining lysate. This study included 32 patients with early stage hormone receptors-positive BC. Remaining OSNA lysates were prepared for targeted RNA-sequencing analysis. Identification of differentially expressed genes (DEGs) was performed by DESeq2 in R and data analysis in STATA. The results show that, in metastatic SLNs, several genes were upregulated: KRT7, VTCN1, CD44, GATA3, ALOX15B, RORC, NECTIN2, LRG1, CD276, FOXM1 and IGF1R. Hierarchical clustering analysis revealed three different clusters. The identified DEGs codify proteins mainly involved in cancer aggressiveness and with impact in immune response. The overexpression of the immune suppressive genes VTCN1 and CD276 may explain that no direct evidence of activation of immune response in metastatic SLNs was found. We show that OSNA results may be improved incorporating microenvironment-related biomarkers that may be useful in the future for prognosis stratification and immunotherapy selection. As OSNA assay is being implemented for SLNs staging in other cancers, this approach could also have a wider utility.

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Exploring the lymph node’s microenvironment for personalized management of Luminal A breast cancer

Gante

Ribeiro

Mendes

et al. 2022

Preprint

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Background Lymph nodes (LNs) are the main doorway for tumor cell metastases from the primary site and its evaluation is a major prognostic factor. The One Step Nucleic Acid Amplification (OSNA) is being adopted worldwide for sentinel-LNs (SLNs) staging in breast cancer (BC). SLNs´ OSNA lysate may be used for gene expression studies, being the potentially ideal samples to search for new markers related to immune response. Using a targeted gene expression approach, we aim to identify transcriptomic patterns of SLNs immune response and biomarkers that may improve risk stratification and personalized therapy for patients with Luminal A BC. Methods This was an observational, prospective, pilot study that included 32 patients with Luminal A early-stage BC: 16 patients with OSNA negative SLNs and 16 patients with OSNA positive SLNs. After the OSNA assay, rather than being discarded, the remaining OSNA lysates were prepared for target RNA sequencing (RNA-seq) analysis, using the Oncomine™ Immune Response Research Assay. Identification of differentially expressed genes (DEGs) for group comparisons was performed by DESeq2 R package (version 1.36.0) in R (version 4.2.0). Data analysis was performed using STATA software, version 13.1, and statistical significance was set at p < 0.05. Results In Luminal A BC patients, several genes were upregulated in metastatic SLNs, including KRT7, VTCN1, CD44, GATA3, ALOX15B, RORC and NECTIN2. In macrometastatic SLNs, LRG1, CD276, FOXM1 and IGF1R were also upregulated. In metastatic SLNs, higher values of total tumor load (TTL) correlated with a higher expression of most DEGs. Hierarchical clustering analysis revealed three different clusters, not coincident with pN0, pN1mi and pN1 classification. Conclusions A better understanding of the complex interplay between cancer cells and host immunity is essential for the choice of personalized treatments in Luminal A BC. The identified DEGs codify proteins mainly involved in cancer aggressiveness and with impact in immune response. These DEGs may improve prognosis accuracy and increase the efficacy and safety of targeted therapies in Luminal A BC patients. As OSNA assay is being implemented for SLNs staging in other cancers, RNA-seq in the OSNA lysate could also have a wider utility.

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P01. Can one-step nucleic acid amplification assay predict 4 or more positive axillary lymph node involvement in breast cancer patients: A single centre retrospective study

Cited by 3 publications

References 0 publications

Exploring the lymph node’s microenvironment for personalized management of luminal A breast cancer

Exploring the lymph node’s microenvironment for personalized management of luminal A breast cancer

One Step Nucleic Acid Amplification (OSNA) Lysate Samples Are Suitable to Establish a Transcriptional Metastatic Signature in Patients with Early Stage Hormone Receptors-Positive Breast Cancer

Exploring the lymph node’s microenvironment for personalized management of Luminal A breast cancer

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