Liquid Biopsy in Breast Cancer (2nd Edition)

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Biomarkers".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 3820

Special Issue Editors


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Guest Editor
Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece
Interests: circulating tumor cells (CTCs); biomarkers; tumor heterogeneity; anti-tumor immunity; peripheral immune response; tumor immune evasion; immune checkpoints; breast cancer; lung cancer
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Guest Editor
Head, Department of Medical Oncology, University of Crete Medical School, Heraklion, Greece
Interests: biology of early breast cancer; clinical trials; circulating tumor cells; adjuvant chemotherapy; chemotherapy for metastatic breast cancer; endocrine resistance; mTOR inhibitors; CDK4/6 inhibitors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

We are excited to invite you to contribute to this Special Issue—the second edition of “Liquid Biopsy in Breast Cancer” (https://www.mdpi.com/journal/cancers/special_issues/Liquid_Biopsy_Breast_Cancer).

Liquid biopsy is being increasingly recognized as a valuable non-invasive tool for the management of patients with solid tumors. It mainly includes the analysis of intact circulating tumor cells (CTCs), nucleic acids such as circulating tumor DNA (ctDNA) and circulating miRNAs, as well as exosomes/extracellular vesicles. CTC enumeration emerged as the first liquid biopsy analyte with clinical relevance in breast cancer (BC) in as early as 2004, and, since then, large clinical trials have verified the role of CTCs in the prediction of relapse or disease progression, as well as the survival of metastatic BC patients. Beyond enumeration, CTC characterization at the protein/RNA/DNA level has been widely used to provide information about tumor heterogeneity and to uncover novel mechanisms of metastasis and resistance to current therapies. Moreover, different liquid biopsy analytes provide independent yet complementary information; thus, their combined use can better reflect tumor heterogeneity and improve disease monitoring in real time. The analysis of ctDNA has gained significant attention mainly due to its high reproducibility, and it is increasingly utilized in BC clinical trials to monitor treatment outcomes. Recently, a PIK3CA companion diagnostic assay was approved by the FDA to detect PIK3CA mutations in the ctDNA of BC patients eligible for treatment with alpelisib. Other liquid biopsy analytes such as circulating miRNAs and exosomes/extracellular vesicles are also widely used in BC research, but their clinical validity and utility are still under investigation.

This Special Issue of Cancers welcomes contributions that present new data and address or discuss liquid biopsy biomarkers with prognostic and/or predictive relevance in BC. This Special Issue will also focus on translational research that will shed light on the role of CTCs and other liquid biopsy analytes in BC metastatic progression, as well as resistance to endocrine therapy, chemotherapy, or targeted therapies. Studies discussing the development of new liquid biopsy assays are also welcome. Of great interest are reports on the longitudinal assessment of liquid biopsy, as well as studies utilizing liquid biopsy to identify potential novel therapeutic targets.

Dr. Maria Papadaki
Prof. Dr. Dimitrios Mavroudis
Guest Editors

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Keywords

  • liquid biopsy
  • liquid biomarkers
  • precision oncology
  • disease monitoring
  • treatment monitoring
  • tumor heterogenei-ty
  • circulating tumor cells (CTCs)
  • circulating tumor DNA (ctDNA)
  • circulating miRNAs
  • exosomes
  • extracellular vesicles (EVs)

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Related Special Issue

Published Papers (2 papers)

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16 pages, 1640 KiB  
Article
Prognostic Value of Fas/Fas Ligand Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Patients with Metastatic Breast Cancer
by Maria A. Papadaki, Eleni Papadaki, Sofia Chatziavraam, Despoina Aggouraki, Kleita Michaelidou, Charalampos Fotsitzoudis, Maria Vassilakopoulou, Dimitrios Mavroudis and Sofia Agelaki
Cancers 2024, 16(17), 2927; https://doi.org/10.3390/cancers16172927 - 23 Aug 2024
Cited by 1 | Viewed by 1336
Abstract
The Fas/Fas ligand (FasL) system is a major apoptosis-regulating pathway with a key role in tumor immune surveillance and metastasis. The expression of Fas/FasL on mammary tumor tissues holds prognostic value for breast cancer (BC) patients. We herein assessed Fas/FasL expression on circulating [...] Read more.
The Fas/Fas ligand (FasL) system is a major apoptosis-regulating pathway with a key role in tumor immune surveillance and metastasis. The expression of Fas/FasL on mammary tumor tissues holds prognostic value for breast cancer (BC) patients. We herein assessed Fas/FasL expression on circulating tumor cells (CTCs) and matched peripheral blood mononuclear cells (PBMCs) from 98 patients with metastatic BC receiving first-line treatment. Fas+, FasL+, and Fas+/FasL+ CTCs were identified in 88.5%, 92.3%, and 84.6% of CTC-positive patients, respectively. In addition, Fas+/FasL+, Fas-/FasL+, and Fas-/FasL- PBMCs were identified in 70.3%, 24.2%, and 5.5% of patients, respectively. A reduced progression-free survival (PFS) was revealed among CTC-positive patients (median PFS: 9.5 versus 13.4 months; p = 0.004), and specifically among those harboring Fas+/FasL+ CTCs (median PFS: 9.5 vs. 13.4 months; p = 0.009). On the other hand, an increased overall survival (OS) was demonstrated among patients with Fas+/FasL+ PBMCs rather than those with Fas-/FasL+ and Fas-/FasL- PBMCs (median OS: 35.7 vs. 25.9 vs. 14.4 months, respectively; p = 0.008). These data provide for the first time evidence on Fas/FasL expression on CTCs and PBMCs with significant prognostic value for patients with metastatic BC, thus highlighting the role of the Fas/FasL system in the peripheral immune response and metastatic progression of BC. Full article
(This article belongs to the Special Issue Liquid Biopsy in Breast Cancer (2nd Edition))
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19 pages, 16187 KiB  
Article
Exploring Canine Mammary Cancer through Liquid Biopsy: Proteomic Profiling of Small Extracellular Vesicles
by Adriana Alonso Novais, Guilherme Henrique Tamarindo, Luryan Mikaelly Minotti Melo, Beatriz Castilho Balieiro, Daniela Nóbrega, Gislaine dos Santos, Schaienni Fontoura Saldanha, Fabiana Ferreira de Souza, Luiz Gustavo de Almeida Chuffa, Shay Bracha and Debora Aparecida Pires de Campos Zuccari
Cancers 2024, 16(14), 2562; https://doi.org/10.3390/cancers16142562 - 17 Jul 2024
Cited by 1 | Viewed by 2030
Abstract
(Background). Canine mammary tumors (CMTs) have emerged as an important model for understanding pathophysiological aspects of human disease. Liquid biopsy (LB), which relies on blood-borne biomarkers and offers minimal invasiveness, holds promise for reflecting the disease status of patients. Small extracellular vesicles (SEVs) [...] Read more.
(Background). Canine mammary tumors (CMTs) have emerged as an important model for understanding pathophysiological aspects of human disease. Liquid biopsy (LB), which relies on blood-borne biomarkers and offers minimal invasiveness, holds promise for reflecting the disease status of patients. Small extracellular vesicles (SEVs) and their protein cargo have recently gained attention as potential tools for disease screening and monitoring. (Objectives). This study aimed to isolate SEVs from canine patients and analyze their proteomic profile to assess their diagnostic and prognostic potential. (Methods). Plasma samples were collected from female dogs grouped into CMT (malignant and benign), healthy controls, relapse, and remission groups. SEVs were isolated and characterized using ultracentrifugation (UC), nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). Proteomic analysis of circulating SEVs was conducted using liquid chromatography–mass spectrometry (LC–MS). (Results). While no significant differences were observed in the concentration and size of exosomes among the studied groups, proteomic profiling revealed important variations. Mass spectrometry identified exclusive proteins that could serve as potential biomarkers for mammary cancer. These included Inter-alpha-trypsin inhibitor heavy chain (ITIH2 and ITI4), phosphopyruvate hydratase or alpha enolase (ENO1), eukaryotic translation elongation factor 2 (eEF2), actin (ACTB), transthyretin (TTR), beta-2-glycoprotein 1 (APOH) and gelsolin (GSN) found in female dogs with malignant tumors. Additionally, vitamin D-binding protein (VDBP), also known as group-specific component (GC), was identified as a protein present during remission. (Conclusions). The results underscore the potential of proteins found in SEVs as valuable biomarkers in CMTs. Despite the lack of differences in vesicle concentration and size between the groups, the analysis of protein content revealed promising markers with potential applications in CMT diagnosis and monitoring. These findings suggest a novel approach in the development of more precise and effective diagnostic tools for this challenging clinical condition. Full article
(This article belongs to the Special Issue Liquid Biopsy in Breast Cancer (2nd Edition))
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