High serum levels of leucine-rich α-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer.

Background: Leucine-rich α-2 glycoprotein 1 (LRG-1) is a secreted glycoprotein that is mainly produced in the liver. Elevated levels of LRG-1 are found in a multitude of pathological conditions including eye diseases, diabetes, infections, autoimmune diseases, and cancer. In patients with early breast cancer (BC), high intratumoral LRG-1 protein expression levels are associated with reduced survival.

Ratios of monocytes and neutrophils to lymphocytes in the blood predict benefit of CDK4/6 inhibitor treatment in metastatic breast cancer.

Biomarkers to identify metastatic breast cancer (mBC) patients resistant to CDK4/6 inhibition (CDK4/6i) are currently missing. We evaluated the usefulness of the monocyte-to-lymphocyte ratio (MLR), the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) as predictive markers for de novo resistance to CDK4/6i. Various blood cell counts and MLR, NLR, PLR were recorded before treatment initiation (baseline) and four weeks later from 97 mBC patients receiving endocrine therapy (ET) alone or in combination with CDK4/6i.

Correlation between Imaging Markers Derived from PET/MRI and Invasive Acquired Biomarkers in Newly Diagnosed Breast Cancer.

Purpose: Evaluate the diagnostic potential of [F]FDG-PET/MRI data compared with invasive acquired biomarkers in newly diagnosed early breast cancer (BC).

Methods: Altogether 169 women with newly diagnosed BC were included. All underwent a breast- and whole-body [F]FDG-PET/MRI for initial staging.

In Early Breast Cancer, the Ratios of Neutrophils, Platelets and Monocytes to Lymphocytes Significantly Correlate with the Presence of Subsets of Circulating Tumor Cells but Not with Disseminated Tumor Cells.

Circulating tumor cells (CTCs) crosstalk with different blood cells before a few of them settle down as disseminated tumor cells (DTCs). We evaluated the correlation between CTC subtypes, DTCs and the neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and monocyte to lymphocyte ratio (MLR) for better prognostication of 171 early staged diagnosed breast cancer (BC) patients. -Clinical data and blood values before treatment were retrospectively recorded, representing the 75% percentile, resulting in 3.

Combinatorial Power of cfDNA, CTCs and EVs in Oncology.

Liquid biopsy is a promising technique for clinical management of oncological patients. The diversity of analytes circulating in the blood useable for liquid biopsy testing is enormous. Circulating tumor cells (CTCs), cell-free DNA (cfDNA) and extracellular vesicles (EVs), as well as blood cells and other soluble components in the plasma, were shown as liquid biopsy analytes.

Programmed death receptor ligand-2 (PD-L2) bearing extracellular vesicles as a new biomarker to identify early triple-negative breast cancer patients at high risk for relapse.

Purpose: Based on the tumor-promoting features of extracellular vesicles (EV) and PD-L1/2-bearing EV subpopulations (PD-L1/2), we evaluated their potential as surrogate markers for disease progression or eligibility criteria for PD-1 immune checkpoint inhibition (ICI) approaches in early triple-negative breast cancer (TNBC).

Methods: After enrichment of EV from plasma samples of 56 patients before and 50 after chemotherapy (CT), we determined levels of EV particle number and PD-L1/2 by nanoparticle tracking analysis or ELISA and associated the results with clinical status/outcome and the presence of distinct circulating tumor cells (CTC) subpopulations.

Results: Compared to healthy controls, patients had a tenfold higher EV concentration and significantly elevated PD L2 but not PD L1 levels.

Systematic Evaluation of 3'Untranslated Region Variants in Locally Advanced, Non-Metastatic Breast Cancer Patients: UTR-1, 2 or UTR-4 are Predictors for Therapy and Disease Outcome.

Despite major improvements in diagnostics and therapy in early as well as in locally advanced breast cancer (LABC), metastatic relapse occurs in about 20% of patients, often explained by early micro-metastatic spread into bone marrow by disseminated tumor cells (DTC). Although neoadjuvant chemotherapy (NACT) has been a successful tool to improve overall survival (OS), there is growing evidence that various environmental factors like the non-classical human leukocyte antigen-G (HLA-G) promotes cancer invasiveness and metastatic progression. HLA-G expression is associated with regulatory elements targeting certain single-nucleotide polymorphisms (SNP) in the 3' untranslated region (UTR), which arrange as haplotypes.

Single HER2-positive tumor cells are detected in initially HER2-negative breast carcinomas using the DEPArray™-HER2-FISH workflow.

Background: In breast cancer (BC), overexpression of HER2 on the primary tumor (PT) is determined by immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) to stratify samples as negative, equivocal and positive to identify patients (pts) for anti-HER2 therapy. CAP/ASCO guidelines recommend FISH for analyzing HER2/neu (ERBB2) gene amplification and for resolving equivocal HER2 IHC results. However, pre-analytical and analytical aspects are often confounded by sample related limitations and tumor heterogeneity and HER2 expression may differ between the PT and circulating tumor cells (CTCs), the precursors of metastasis.

Prognostic Significance of Methylation in Plasma Cell-Free DNA in Advanced High-Grade Serous Ovarian Cancer.

Background: Epigenetic alterations in ctDNA are highly promising as a source of novel potential liquid biopsy biomarkers and comprise a very promising liquid biopsy approach in ovarian cancer, for early diagnosis, prognosis and response to treatment.

Methods: In the present study, we examined the methylation status of six gene promoters (, , , , and in high-grade serous ovarian cancer (HGSOC). We evaluated the prognostic significance of DNA methylation of these six gene promoters in primary tumors (FFPEs) and plasma cfDNA samples from patients with early, advanced and metastatic HGSOC.

Association of Soluble B7-H4 and Circulating Tumor Cells in Blood of Advanced Epithelial Ovarian Cancer Patients.

Introduction: Epithelial ovarian cancer (EOC) is the deadliest gynecologic malignancy worldwide. Reliable predictive biomarkers are urgently needed to estimate the risk of relapse and to improve treatment management. Soluble immune-checkpoints in EOC are promising molecules serving as prognostic biomarkers accessible liquid biopsy.

Image-Based Identification and Genomic Analysis of Single Circulating Tumor Cells in High Grade Serous Ovarian Cancer Patients.

In Ovarian Cancer (OC), the analysis of single circulating tumor cells (sCTCs) might help to investigate genetic tumor evolution during the course of treatment. Since common CTC identification features failed to reliably detect CTCs in OC, we here present a workflow for their detection and genomic analysis. Blood of 13 high-grade serous primary OC patients was analyzed, using negative immunomagnetic enrichment, followed by immunofluorescence staining and imaging for Hoechst, ERCC1, CD45, CD11b and cytokeratin (CK) and sCTC sorting with the DEPArray NxT.

Disseminated tumour cells from the bone marrow of early breast cancer patients: Results from an international pooled analysis.

Purpose: Presence of disseminated tumour cells (DTCs) in the bone marrow (BM) has been described as a surrogate of residual disease in patients with early breast cancer (EBC). PADDY (Pooled Analysis of DTC Detection in Early Breast Cancer) is a large international analysis of pooled data that aimed to assess the prognostic impact of DTCs in patients with EBC.

Experimental Design: Individual patient data were collected from 11 centres.

Integrative statistical analyses of multiple liquid biopsy analytes in metastatic breast cancer.

Background: Single liquid biopsy analytes (LBAs) have been utilized for therapy selection in metastatic breast cancer (MBC). We performed integrative statistical analyses to examine the clinical relevance of using multiple LBAs: matched circulating tumor cell (CTC) mRNA, CTC genomic DNA (gDNA), extracellular vesicle (EV) mRNA, and cell-free DNA (cfDNA).

Methods: Blood was drawn from 26 hormone receptor-positive, HER2-negative MBC patients.

Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer.

Background: Neuropilin-1 (NRP-1) is a transmembrane protein that acts as a multifunctional non-tyrosine kinase receptor with an established role in development and immunity. NRP-1 also regulates tumor biology, and high expression levels of tissue NRP-1 have been associated with a poor prognosis. Recently, ELISA-based quantification of soluble NRP-1 (sNRP-1) has become available, but little is known about the prognostic value of sNRP-1 in malignancies.

An Observational Study on Breast Cancer Survival and Lifestyle Related Risk Factors.

Background/aim: Breast cancer survivors are increasingly interested in lifestyle modifications in order to reduce the risk of recurrence and mortality. Therefore, we aimed to study the association between survival and lifestyle related risk factors such as obesity, alcohol intake, smoking, medication and atopic diseases.

Patients And Methods: In this observational single center study, clinicopathological parameters of 635 women with primary breast cancer were sampled.

Longitudinal Multi-Parametric Liquid Biopsy Approach Identifies Unique Features of Circulating Tumor Cell, Extracellular Vesicle, and Cell-Free DNA Characterization for Disease Monitoring in Metastatic Breast Cancer Patients.

Dynamics of mRNA from circulating tumor cells (CTCs), mRNA from extracellular vesicles (EVs), and cell-free DNA (cfDNA) were assessed to examine the relevance of a longitudinal multi-parametric liquid biopsy strategy. Eighteen milliliters of blood was drawn from 27 hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) patients at disease progression and at two subsequent radiologic staging time points. CTC mRNA and EV mRNA were analyzed using multi-marker qPCR, and cfDNA was analyzed using targeted next-generation sequencing (NGS).

Liquid Biopsies to Evaluate Immunogenicity of Gynecological/Breast Tumors: On the Way to Blood-Based Biomarkers for Immunotherapies.

Background: Despite the assumption of breast cancer (BC) as a cold, non-immunogenic tumor, immune checkpoint inhibitor (ICI) therapy is favorable for a subgroup of patients. Immunohistochemical assessment of the programmed cell death ligand 1 (PD-L1) is the only approved companion diagnostic for anti-PD-L1 therapy in metastatic triple-negative BC; however, challenges regarding the standardization of PD-L1 scoring in tumor tissue still remain. Consequently, to select patients most likely to respond to ICI, blood-based biomarkers are urgently needed.

Circulating Tumor Cells Expressing the Prostate Specific Membrane Antigen (PSMA) Indicate Worse Outcome in Primary, Non-Metastatic Triple-Negative Breast Cancer.

We analyzed mRNA profiles of prostate cancer related genes in circulating tumor cells (CTCs) of primary, non-metastatic triple-negative breast cancer (TNBC) patients (pts) before and after neoadjuvant chemotherapy to elucidate the potential of prostate cancer targets in this BC subgroup. Blood from 41 TNBC pts ( = 41 before / 26 after therapy) was analyzed for CTCs applying the AdnaTest EMT-2/Stem Cell Select. Multimarker RT-qPCR allowed the detection of the prostate specific antigen , the prostate specific membrane antigen , full-length androgen receptor (), and AR splice-variant seven ().

A proposal for score assignment to characterize biological processes from mass spectral analysis of serum.

Introduction: Most diseases involve a complex interplay between multiple biological processes at the cellular, tissue, organ, and systemic levels. Clinical tests and biomarkers based on the measurement of a single or few analytes may not be able to capture the complexity of a patient's disease. Novel approaches for comprehensively assessing biological processes from easily obtained samples could help in the monitoring, treatment, and understanding of many conditions.

6-Color/1-Target Immuno-SERS Microscopy on the Same Single Cancer Cell.

There is an urgent clinical need for multicolor imaging of single cancer cells (no ensemble averaging) for identifying heterogenous expression of predictive biomarkers. Specifically, the comprehensive characterization of single disseminated tumor cells (sDTCs) responsible for metastatic relapse is the key to personalized therapy for patients. Current bioimaging methods lack the necessary multicolor capacity and suffer from background/autofluorescence.

Molecular characterization of circulating tumour cells identifies predictive markers for outcome in primary, triple-negative breast cancer patients.

mRNA profiles of circulating tumour cells (CTCs) were analysed in patients with triple-negative breast cancer (TNBC) (pts) before (BT) and after therapy (AT) to identify additional treatment options. 2 × 5 mL blood of 51 TNBC pts and 24 non-TNBC pts (HR+/HER2-; HR-/HER2+) was analysed for CTCs using the AdnaTest EMT-2/Stem Cell Select™, followed by mRNA isolation and cDNA analysis for 17 genes by qPCR PIK3CA, AKT2, MTOR and the resistance marker AURKA and ERCC1 were predominantly expressed in all breast cancer subtypes, the latter ones especially AT. In TNBC pts, ERBB3, EGFR, SRC, NOTCH, ALK and AR were uniquely present and ERBB2+/ERBB3 + CTCs were found BT and AT in about 20% of cases.