Research History, Current Trends, and Future Prospects of Liquid Biopsy in Triple-Negative Breast Cancer: An Analysis from a Global Perspective

Research History, Current Trends, and Future Prospects of Liquid Biopsy in Triple-Negative Breast Cancer: An Analysis from a Global Perspective | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Research History, Current Trends, and Future Prospects of Liquid Biopsy in Triple-Negative Breast Cancer: An Analysis from a Global Perspective Yi Qu, Jixian Wan, Ruihan Li, Xinyuan Li, Han Li, Yang Li, Shengnan Huang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4203189/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Liquid biopsy has emerged as a significant technique in the field of triple-negative breast cancer, garnering widespread attention since 2012. Despite this, there remains a notable absence of bibliometric assessment in this area. This study screened 506 pieces of literature obtained from Web of Science (WoS) searches and selected 347 papers published between 2012 and 2024. Various software tools, including VOSviewer , CiteSpace , Bibliomatrix , and Scimago Graphica were used to visualize the results of the analyses. Through careful examination of visual graphs, this study conducted in-depth profiling mining, suggesting great potential and promise in this area. The linkage map of countries highlights the central roles played by the USA and China in this field over the past twelve years. Furthermore, the analysis of literature co-citations reveals a predominant focus on subtypes, cell models, and targeted therapies. Keyword analysis indicates previous emphasis on sensitive targets and advancements in the nano-field. Moreover, the evolution of keywords over time illustrates a transition from mechanistic inquiries to investigations spanning diagnosis, immunotherapy, and prognosis. These results offer valuable insights into the research process and potential future directions. Additionally, this paper integrates keywords, co-cited cores, coupling centrality, and visual analysis results of the most cited literature, using techniques such as timeline graph clustering and emergent words. Major hotspots are summarised, such as "biomarker", "target", "biological model", and "Immunotherapy inhibitors". Triple-negative breast cancer (TNBC) Liquid biopsy Bibliometrics Exosomes Circulating tumor cells (CTCs) Circulating tumor DNA (ctDNA) Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 1. Introduction Breast cancer, recognized as the most frequently diagnosed malignancy in women, displays significant diversity across histologic classification, etiology, pathogenesis, clinical manifestation, therapeutic modalities, and treatment outcomes [ 1 ]. Among its various subtypes, triple-negative breast cancer (TNBC) accounts for approximately 15–20 percent. Distinguished by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER-2), TNBC emerges as a remarkably heterogeneous disease. TNBC manifests aggressively, disproportionately affecting women in younger and premenopausal age groups [ 2 ]. Consequently, previous studies have indicated that TNBC has a worse prognosis compared to other breast cancer subtypes, leading to lower survival rates for patients [ 3 , 4 ]. Currently, the absence of early diagnostic markers for TNBC poses a significant challenge, with percutaneous transluminal biopsy serving as the gold standard but encountering key limitations. Therefore, there exists an urgent need for new methods facilitating early TNBC diagnosis [ 5 ]. In contrast to tissue biopsy, liquid biopsy presents numerous advantages, including non-invasiveness, ease of operation, reduced risk, detection of minute lesions, and comprehensive tumor profiling. As such, attention has shifted towards liquid biopsy as a promising alternative. Liquid biopsy, a non-invasive technique used for tumor detection, retrieves tumor-related information through the analysis of body fluids such as blood, urine, and ascites. Notably, it has demonstrated successful applications in detecting multiple cancer types, including TNBC [ 6 , 7 ]. This study aimed to use literature visualisation to elucidate research hotspots and provide novel insights into the application of liquid biopsy in TNBC. Bibliometrics is one of the most important methods for literature visualisation, having previously played an important role in hotspot mining across a wide range of solid tumors, including lung cancer and endometrial cancer [ 8 , 9 ]. As an interdisciplinary science of quantitative analysis of knowledge carriers, bibliometrics primarily measures the number of documents (particularly journal papers and citations), the number of authors (individual or groups), and the number of words (document identifiers, mostly descriptors). Using software tools to analyse relevant literature, this paper provides an intuitive and comprehensive overview for researchers, summarizing current hotspots and addressing existing challenges to provide directions for future research (Fig. 1 ). 2. Materials and methods 2.1 Sources of data and search strategies Bibliometric analysis was conducted using the Web of Science (Clarivate Analytics). To mitigate potential deviations due to rapid database updates, literature retrieval was completed within a single day on 3 January 2024. Search terms were refined using Medical Subject Headings as follows: ((TS=(liquid-biopsy) OR TS=(fluid-biopsy) OR TS=(circulating-tumo*-cell*) OR TS=(CTC*) OR TS= (cell-free-tumo*- DNA*) OR TS=(cfDNA*) OR TS=(ctDNA*) OR TS=(circulating-tumo*-DNA*) OR TS=(exosome*)) AND (TS= (triple-negative-breast-cancer*) OR TS=( triple-negative-breast- Neoplasm*))). Only original articles and reviews written in English were considered among various publication types. Two researchers (QY and LRH) independently searched raw data and subsequently discussed any discrepancies, resulting in a final concordance of 0.87, indicating substantive consistency. 2.2 Data Collection and Cleaning Initially, a search was performed in Web of Science (Clarivate Analytics) using search terms limited to original articles and reviews written in English. Subsequently, the "full record with cited references" of all retrieved publications was exported. Finally, the resulting data were imported into bibliometric analysis software for subsequent analysis and visualization. A detailed data cleansing strategy is illustrated in Fig. 2 . 3. Result Comprehensively understanding the field of liquid biopsy in TNBC and staying updated with the latest research poses increasing challenges due to rapidly evolving technology. To gain an overview of global trends regarding the use of liquid biopsy in TNBC, bibliometric analysis was used to visualise and analyse data about countries, journals, literature co-citations, couplings, timeline graphs, and emergent terms along a temporal axis, spanning historical trends, current hotspots, to future directions. 3.1 Overview A total of 347 papers were included in this study, including 286 original articles (82.4%) and 61 review papers (17.6%). The number of publications was fitted using the model: y = y 0 + A 1 *exp((x-x 0 )/t 1 ), with the fitting results displayed in Fig. 3 . The figure summarises the fluctuation in the number of publications between 2012 and 2023. Additionally, a curve was fitted using a model where the dark red band represents the 95% confidence band of the fitted curve, and the light red band depicts the 95% prediction zone of the fitted curve. The fitting results suggest a rapid development stage in the field, with a projected increase to 160 related papers by 2025. 3.2 Integration and comparison of global cooperation networks Table 1 Top 10 countries according to publications Country publications Citations Total link strength(TLS) Average Citation/Document USA 130 4863 81 37.4 China 104 3150 30 30.3 Germany 28 710 31 25.4 Italy 26 815 22 31.3 India 19 562 15 29.6 South Korea 16 342 7 21.4 United Kingdom 14 368 23 26.3 Japan 13 232 6 17.8 Australia 12 171 11 14.3 Canada 12 181 9 15.1 A total of 23 eligible countries with a minimum of 4 documents were screened.The TNBC multi-country collaborative network is illustrated in Fig. 4 , in which circle sizes represent the number of documents, while the thickness of the line indicates the degree of connectivity for each country. We can found that China and the USA forming the initial collaborative network. The USA leads in publications and has the most collaborating countries, particularly with China. China ranks second in publications but exhibits low total link strength (TLS). The top 10 countries, ranked by the number of published papers, are listed in Table 1 , with the USA (130, 28.0%) in the first place, followed by China (104, 22.6%), and Germany (28, 6.1%). Notably, both the USA and China have over 100 publications, indicating their leadership in triple-negative liquid biopsy research. Furthermore, total link strength with other countries is calculated, with the USA (TLS: 81) leading, followed closely by Germany (TLS: 31), and China (TLS: 30). 3.3 Mining and summarisation of hot publications Table 2 Top 10 publications by total citations Rank Title DOI Total Citations TC per Year Normalized TC 1 Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis https://doi.org/10.1016/j.gendis.2018.05.001 506 72.3 5.67 2 Hypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis https://doi.org/10.1073/pnas.1410041111 351 31.9 3.27 3 Metastatic and triple-negative breast cancer: challenges and treatment options https://doi.org/10.1007/s13346-018-0551-3 306 43.7 3.43 4 Tumor microenvironment: Challenges and opportunities in targeting metastasis of triple negative breast cancer https://doi.org/10.1016/j.phrs.2020.104683 220 44 4.94 5 Homophilic CD44 Interactions Mediate Tumor Cell Aggregation and Polyclonal Metastasis in Patient-Derived Breast Cancer Models https://doi.org/10.1158/2159-8290.CD-18-0065 219 36.5 4.24 6 Exosome-mediated siRNA delivery to suppress postoperative breast cancer metastasis https://doi.org/10.1016/j.jconrel.2019.12.005 204 40.8 4.58 7 miR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity https://doi.org/10.18632/oncotarget.5192 200 20 3.22 8 Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells https://doi.org/10.1111/cas.14181 183 30.5 3.54 9 Functional exosome-mediated co-delivery of doxorubicin and hydrophobically modified microRNA 159 for triple-negative breast cancer therapy https://doi.org/10.1186/s12951-019-0526-7 180 30 3.48 10 Exosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells https://doi.org/10.1016/j.ejca.2013.01.017 170 14.2 2.08 Table 2 presents the top 10 highly cited publications relevant to the analysis. The most cited document titled "Breast cancer development and progression: risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis" summarizes a total of 373 papers discussing risk factors, common mutation sites, classification and early symptoms, molecular subtypes, available targeted therapies, clinical staging, and survival in breast cancer fundamental issues [ 10 ]. A total of 21 co-citations were analysed with a minimum threshold of 20 citations for co-cited literature, resulting in the grouping of these citations into three clusters (Fig. 5 ).Circles represent the more cited literature, with the size of the circle indicating the number of citations. Different colors represent different clusters, and each cluster of cited literature has the same focus, which is marked on the side. The first cluster, marked in red, focuses on targeted therapies for different subtypes of TNBC. This indicates that targeted therapies and related targeted therapeutic agents are currently a prominent research topic. The second cluster, highlighted in green, emphasizes the potential of CTCs and liquid biopsy in the detection and prognosis of TNBC. Lastly, the third cluster, denoted in blue, indicates the application of exosomes as biomarkers and therapeutic targets in TNBC research. Table 3 Top 10 coupled literature by centrality Rank Centerity Year Cited References 1 0.22 2017 Siegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI 10.3322/caac.21387 2 0.22 2013 Dawson SJ, 2013, NEW ENGL J MED, V368, P1199, DOI 10.1056/NEJMoa1213261 3 0.22 2019 Yu MY, 2019, CANCER SCI, V110, P3173, DOI 10.1111/cas.14181 4 0.19 2011 Lehmann BD, 2011, J CLIN INVEST, V121, P2750, DOI 10.1172/JCI45014 5 0.18 2019 Garcia-Murillas I, 2019, JAMA ONCOL, V5, P1473, DOI 10.1001/jamaoncol.2019.1838 6 0.18 2015 Madic J, 2015, INT J CANCER, V136, P2158, DOI 10.1002/ijc.29265 7 0.16 2010 Carey L, 2010, NAT REV CLIN ONCOL, V7, P683, DOI 10.1038/nrclinonc.2010.154 8 0.15 2018 Stevic I, 2018, BMC MED, V16, P0, DOI 10.1186/s12916-018-1163-y 9 0.15 2014 Bidard FC, 2014, LANCET ONCOL, V15, P406, DOI 10.1016/S1470-2045(14)70069-5 10 0.14 2018 Li YM, 2018, CELL DEATH DIS, V9, P0, DOI 10.1038/s41419-017-0030-7 Figure 6 shows a trend of increasing concentration and heightened centrality of couplings increases over time. The top 10 coupled literatures, ranked by centrality, are listed in Table 3 . The most centrally coupled literature is “Cancer Statistics, 2017” demonstrating its comprehensive and fundamental nature [ 11 ]. This literature not only presents statistical evidence of a consistent decline in cancer mortality over the past 20 years but also predicts a reduction in racial disparities impacting cancer mortality. Thus, its comprehensiveness provides a basis for future research. Ranked third, “Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells”, exhibits significant coupling centrality despite its later publication, suggesting seminal findings and a strong impact. Notably, the literature, “The biology, function, and biomedical applications of exosomes” published in 2020, although ranked 16th, displayed the highest coupling centrality among recent publications [ 12 ]. 3.4 Tracking and analyses of high-level journals Journals with the highest number of publications are represented in different colour blocks, with shades of yellow indicating a greater number of publications for that year (Fig. 7 ). The heatmap reveals a significant increase in liquid biopsy literature starting from 2020. BMC Cancer stands out with a consistently high volume of publications, suggesting ongoing engagement with pertinent research in the field since 2020. Meanwhile, Clinical Cancer Research demonstrates the longest duration of publication activity, spanning multiple years. Table 4 Top 10 journals by publication frequency Rank Sources Publications Local Cited(LC) Average LC/Document IF 1 Cancers 16 234 14.6 5.6 2 International Journal of Molecular Sciences 12 173 14.4 6.2 3 Breast Cancer Research 8 354 44 7.4 4 Breast Cancer Research and Treatment 8 352 44 4.4 5 Clinical Cancer Research 8 628 78.5 12.5 6 Frontiers in Oncology 8 128 16 5.2 7 Scientific Reports 8 282 35.3 4.9 8 Cancer Letters 6 155 25.8 8.9 9 Frontiers in Immunology 5 98 19.6 8 10 BMC Cancer 4 173 43.3 4.3 In Table 4 , Cancers leads with 16 publications and an Impact Factor (IF) of 5.6, focusing on TNBC cancer and CTCs. Following closely is the International Journal of Molecular Sciences with 12 publications and an IF of 6.2, focusing on exosomes, ctDNA, etc. Approximately 24% of the literature reviewed originated from these top 10 academic journals (83/23.9%). Notably, all of these top ten journals have a high IF greater than 3.0, indicating their significant impact over the past twelve years. Clinical Cancer Research stands out with the highest IF of 12.5 and the highest citation rate. 3.5 Summary and organisation of keywords In Fig. 8 , the primary keywords in the field are presented in a timeline graph. The size of each circle represents the frequency of occurrence of the keyword, and its position in the center of the circle indicates the timing of its first appearance. Keywords are divided into clusters based on their co-occurrence strength, with separate clusters displayed on the right side. Keywords are categorized into 9 clusters according to their link strength. Notably, liquid biopsy-associated molecules associated with metastasis in TNBC are highlighted in cluster #0 labelled "metastasis". Exosomes are highlighted in the timeline plot, demonstrating that they are most strongly associated with TNBC metastasis. Additionally, "circulating tumor cells" in Cluster #1 and the "cell-free DNA" in Cluster #5 are both associated with "liquid biopsy" in Cluster #2. "Triple-negative breast cancer" in Cluster #3 is strongly associated with the "androgen receptor" in Cluster #4. Cluster #6, "nanoparticles", around 2019, introduces "nanoparticles," underscoring the deep intersection of nanotechnology with the medical field. Cluster #7 and Cluster #8 primarily focus on drug therapy for TNBC. In Fig. 9 , the top 25 words ranked by intensity over time are presented. The length of the red line segments indicates the duration of the burst word's sudden appearance. Among these "phage ii" (4.08: Strength), "TNBC" (3.00: Strength), and "substage" (2.51: Strength) are the most intense during 2019 and 2020. Particularly noteworthy is the emphasis on the phage ii stage, a key point of the study. Starting in 2022, buzzwords such as "promotes", "poor prognosis" and "biomarkers" have emerged and continued to gain significance. 4. Discussion 4.1 Review of research history This study used a bibliometric analysis approach to systematically review 347 papers published between 2012 and 2023, aiming to provide insights into important publication trends, explore collaborative efforts among researchers, and anticipate future perspectives in the field. The initial step involved analyzing the number of literature references, followed by the fitting of growth curves to record and predict the expansion of literature. The growth curve exhibits a seemingly exponential form, indicating a growing interest and appreciation for the field among researchers in recent years. At the country level, the USA ranks first, followed by China. Additionally, the USA demonstrates close collaborations with global countries, fostering a diverse cooperation network, a model worthy of emulation by other nations. Beyond political and geographical factors, the USA’s reputable academic environment, strong financial resources, and leading modern scientific foundation likely attract collaboration and foster multi-sourced research outcomes. However, despite Germany’s high publication count, its citation average falls short, signaling a need to prioritize quality over quantity in research endeavors. In terms of literature content, the most cited studies focus on breast stem cells, tumor heterogeneity, cell signaling, epigenetics, and non-coding RNAs, offering researchers a comprehensive understanding of TNBC [ 10 ]. Visual representation of literature co-citations in three clusters improves accuracy in understanding their interconnections. Subsequently, we analyzed the publication heat of journals hosting this literature. Post-2020, many listed journals experienced a significant increase in publication heat, with BMC Cancer consistently maintaining the highest level. Notably, Clinical Cancer Research not only has the highest IF but also the largest number of citations. The journal was the first to publish a study on the application of liquid biopsy in TNBC, specifically a phase I clinical trial evaluating the efficacy of veriparib in combination with beat cyclophosphamide for solid tumor treatment. At the keyword level, expressed through timeline graphs and emergent word analyze, studies applying liquid biopsy in TNBC have progressively deepened since 2012. Initially, the focus of liquid biopsy research in TNBC was mainly on early diagnosis. Currently research focus is shifting towards evaluating the therapeutic effectiveness and predicting the prognosis of TNBC,, particularly evident from 2021 onwards. 4.2 Summary and discussion of popular themes This study presents a comprehensive literature review of liquid biopsy application in TNBC on a temporal axis, integrating visual analysis results to outline major research. Systematically reviewing progress across CTCs, exosomes, and ctDNA branches, we summarize current findings, including the latest diagnostic approaches, and treatment strategyies. These findings aim to assist researchers in navigating current research hotspots and accessing the latest outcomes. 4.2.1 Discussion on circulating tumor cells (CTCs) The most cited publications "Breast cancer development and progression: risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis" highlighted the positive role of blood CTCs in tumourigenesis, with proteomic and genomic analyses informing the basis for further target studies. The potential of CTCs as a biomarker is highlighted in the green cluster in Fig. 5 . Consequently, key themes in the CTCs branch, such as "biomarkers", "targets", "biomodels" and "immunotherapeutic inhibitors" are identified. The migratory properties of CTC present opportunities for enhancing early diagnosis, refining therapeutic approaches through specific target or biomarker identification, and providing prognostic value, including predicting the likelihood of recurrence [ 13 ]. Studies based on liquid biopsy techniques have explored multiple factors contributing to the spread of TNBC tumors. Importantly, CTCs in TNBC patients exhibit plasticity. For example, research has observed an upregulation in the expression of CTC genes that promote TNBC proliferation. This finding suggests the potential use of CTCs as novel targets for early diagnosis and therapeutic interventions [ 14 ]. Clinically, evaluating the number and molecular characteristics of CTCs in early-stage breast cancer patients can provide important tumor information, which is more accurate, timely, and relevant than primary tumor tissue analysis obtained through surgery. This provides new ideas for individualised treatment and may significantly impact clinical decision-making [ 15 , 16 ]. Therapeutically, the single-stranded DNA aptamer (PDGC21-T) demonstrates remarkable selectivity towards TNBC cell lines [ 17 ]. This breakthrough opens avenues for innovation and enhancement of immunotherapy, promising improved efficacy. Recent literature analysis in the field of CTCs reveals that current research is focused on novel approaches to prevent or stop metastases in advanced breast cancer by influencing CTCs formation and survival through relevant signalling pathways. This suggests potential areas for future complementary therapies and improved prognosis [ 18 ]. Recent studies suggest that anti-ICAM1 neutralising antibodies may prevent TNBC cell aggregation and reduce metastasis occurrence [ 19 ]. Meanwhile, the discovery of the anti-metastatic effect of hetIL-15 provides a new complementary solution based on its combination with a post-surgical doxorubicin treatment regimen [ 20 ]. 4.2.2 Discussion on exosomes The blue cluster in Fig. 5 , emphasising exosomes, underscores their potential as biomarkers and alternative therapeutic approaches. The diagnostic role of exosomes in TNBC primarily relies on exosome-derived RNAs.Variations in the levels of various RNAs in exosomes have been found to be associated with the development of TNBC, including lncRNA XIST, circRNA circPSMA1, circEGFR, circHIF1A, BATF2 mRNA, miR-939, miR-194-5p, miR-205-5p, etc [ 21 – 25 ]. Additionally, with the development of proteomics, the diagnostic potential of proteins in exosomes has been extensively studied [ 26 , 27 ]. Previous studies have found a 36kDa calcium-dependent phospholipid-binding protein, annexin A2 (AnxA2), as highly expressed in the exosomes of TNBC patients. This highlights the potential diagnostic significance of exosome-associated proteins, such as AnxA2, in the context of TNBC [ 27 ]. Simultaneously, a notable disparity in the expression of exosomal annexin A2 (exo-AnxA2) was observed among breast cancer cells of different natures, underscoring the potential of exo-AnxA2 as a biomarker for breast cancer [ 26 ]. Moreover, Jung H H et al. found significant alterations in the concentration of MIP-3α and other proteins in exosomes from metastatic breast cancer patients. However, due to the small sample size, these findings do not conclusively reflect breast cancer disease progression and require validation in future studies [ 28 ]. Exosomes serve various biological functions, including mediating cell communication, immunomodulation, anti-inflammation, and promoting angiogenesis. Therapeutically, leveraging exosomes as a tool for TNBC treatment is a feasible approach. In Fig. 8 , Cluster #6 highlights the potential of exosomes as nanocarriers for drug delivery. Their optimal size can prevent removal by phagocytosis, and their excellent biocompatibility minimizes cytotoxic effects and immunogenicity. Exosomes can be used as delivery agents for molecular drugs and can be categorized into two drug-carrying pathways based on the difference in the way of loading drugs, 1) endogenous drug-carrying pathway 2) exogenous drug-carrying pathway. Endogenous drug loading pathway is based on the engineering loading method of parental cells, and the exosome-derived cells are modified; exogenous drug loading pathway is to load drugs directly into exosomes through membrane penetration and other strategies. In general, the exogenous loading route is more efficient. Dilara Uslu et al. demonstrated successful targeting of TNBC using doxorubicin (DOX)-loaded platelet exosomes [ 29 ]. Furthermore, a team of researchers has developed new exosome-delivered drugs, CBSA/siS100A4@Exosome nanoparticles, utilizing exosome-loaded cationic bovine serum albumin (CBSA) conjugated with siS100A4, effectively inhibiting distant metastasis in TNBC, particularly lung metastasis [ 30 ]. Figure 9 , several key words related to prognostic value, such as "survival" and "poor prognosis," highlight the current research focus in the liquid biopsy field. Previous studies have indicated that changes in exosomal contents can serve as indicators of tumor drug resistance. In 2023, Jiulong Ma et al. demonstrated that circRNA EGFR was highly expressed in TNBC cell lines, patient tissues, and plasma exosomes, correlating with piroxicam resistance in patients. This impact was mediated through the circEGFR/miR-1299/EGFR pathway. Silencing circEGFR rendered patients more sensitive to piroxicam, leading to an improved prognosis. This underscores the prognostic, predictive, and therapeutic value of exosomes [ 21 ]. 4.2.3 Discussion on circulating tumor DNA (ctDNA) Shown in Fig. 8 , ctDNA is the main cluster of TNBC liquid biopsy. The primary mutation site in TNBC is TP53 , which plays a pivotal role in driving tumor cell development; followed by PIK3CA [ 31 ]. Released into the circulatory system by tumor cells, ctDNA serves as a non-invasive liquid biopsy and an emerging biomarker for circulating tumors [ 32 ]. Riva. F et al. demonstrated a significant correlation between ctDNA levels and clinical tumor size (continuous variable, P < 0.004), tumor stage (P < 0.03), and high value-added rate, i.e., tumor load [ 33 ]. Next-Generation Sequencing (NGS) has shown high consistency in detecting ctDNA [ 34 – 36 ]. Clinically, Pellerino.A et al. found that ctDNA can identify targeted mutations in metastatic breast cancer and diagnose early metastatic leptomeningeal disease, although substantial data from cerebrospinal fluid liquid biopsy are needed [ 37 ]. Prospective trials suggest that patients remaining positive for ctDNA after surgery following neoadjuvant chemotherapy (NAC) have an increased risk of recurrence compared to those with undetectable ctDNA, inspiring prognostic predictions based on this characteristic [ 38 – 40 ]. Therapeutically, in the absence of distant metastasis, TNBC is typically treated with neoadjuvant chemotherapy (NCT) to reduce tumor size, followed by surgery [ 33 ]. Notably, TNBC patients often achieve a high rate of pathological complete response (pCR) after NCT compared to other types of breast cancer [ 41 ]. By reviewing recent literature, it is concluded that ctDNA can serve as an indicator for assessing tumor evolution, and early kinetic testing of ctDNA can replace other assessments [ 38 , 42 ]. Early screening for breast cancer is crucial for therapeutic outcomes. Therefore, more advanced technology is needed to screen for trace amounts of ctDNA in early body fluids, providing more patients with early-stage breast cancer a chance for a cure. Moreover, there is potential for more personalised therapies targeting the breast immune microenvironment [ 43 ]. 5. Conclusion This paper pioneers the use of bibliometrics to analyze the application of liquid biopsy in TNBC. Through bibliometric analysis, we conducted in-depth profiling mining. The fitted curve, based on the growth in the number of publications over time, suggests significant potential and promise in this area. Visual graphs illustrate that the USA and China have been leaders in TNBC-related liquid biopsy research, with the USA having the highest influence. Journals with the highest publication rates were identified; with Clinical Cancer Research having the longest span of publications. Literature co-citation analysis reveals a focus on subtypes, cell models, and targeted therapies. An analysis of keywords indicates a previous focus on sensitive targets and the nano-field. The evolution of keywords over time demonstrates a shift in focus from mechanism to diagnosis, immunotherapy, and prognosis. In summary, this study objectively and comprehensively demonstrates the research dynamics, hotspots, frontiers, problems, and deficiencies in the field of TNBC-related liquid biopsy through bibliometric analysis. It aims to assist scholars in identifying strengths and weaknesses in this field to enrich and improve its development. 6. Limitations To address potential subjective influences arising from merging databases, this study exclusively collected data from a single database, Web of Science. However, this approach may introduce errors in data collection. Despite using the MeSH word list to optimize the search formula for accuracy, there is inevitably some missing data in this study. While the data in this study were independently collected and cleaned by two researchers, the possibility of subjective bias still exists. In keyword analysis, attempts were made to merge synonyms; however, there may be instances where related words were not merged. Measures have been taken to minimize the impact of unmerged keywords on the final results. 7. Innovations Liquid biopsy-associated molecules in TNBC have undergone extensive studies. Bibliometrics offers objective classification indexes, thereby minimizing subjective factors. In this study, we analyzed all publications from WoS in related fields, revealing the countries of affiliation and journals of publication for each. Visualization tools were employed to intuitively display collaboration networks and research focus, guiding the direction of subsequent research. This study represents the first to utilize bibliometrics to analyze the application of liquid biopsy in TNBC. Additionally, the objective analysis of keywords is another notable aspect of this paper. By utilizing a timeline diagram to visualize the evolution of the field and burst words, the paper scrutinizes both past and current research hotspots while predicting possible future research directions. Declarations Funding This work was supported by the Natural Science Foundation of Shandong Province of China (ZR2021MH215), the Liaocheng Key R&D Plan (2022YDSF37 and 2023YD22), and the Science and Technology Development Project of the Affiliated Hospital of Weifang Medical College (2023FYQ034 and 2023FYM105). Conflicting of interest The authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article. Data Availability This study used data from the Web of Science Core Collection database. Author Contributions Yi Qu, Jixian Wan, Ruihan Li, Xinyuan Li, Han Li, Yang Li, Shengnan Huang, Tingting Zhang performed all data analyses and wrote the original manuscript. Yi Qu wrote and critically reviewed the manuscript. Dawei Yang and Dongliang Chen conceived, designed, and directed the study. All authors reviewed the manuscript. Human and Animal Rights This article does not involve any studies with human participants or animals conducted by any of the authors. Informed Consent For this type of study, informed consent is not required. References Qiu JD, Xue XY, Hu C, Xu H, Kou DQ, Li R, Li M (2016) Comparison of Clinicopathological Features and Prognosis in Triple-Negative and Non-Triple Negative Breast Cancer. J Cancer 7:167–173. https://doi.org/10.7150/jca.10944 Foulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med. https://doi.org/10.1056/NEJMra1001389 . 363:1938-48 Zou Y, Xie J, Zheng S, Liu W, Tang Y, Tian W, Deng X, Wu L, Zhang Y, Wong CW, Tan D, Liu Q, Xie X (2022) Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery. Int J Surg (London England) 107:106936. https://doi.org/10.1016/j.ijsu.2022.106936 Leon-Ferre RA, Goetz MP (2023) Advances in systemic therapies for triple negative breast cancer. BMJ (Clinical Res ed 381:e071674. https://doi.org/10.1136/bmj-2022-071674 Huang Y, Ge H, Zheng M, Cui Y, Fu Z, Wu X, Xia Y, Chen L, Wang Z, Wang S, Xie H (2019) Serum tRNA-derived fragments (tRFs) as potential candidates for diagnosis of nontriple negative breast cancer. J Cell Physiol 235:2809–2824. https://doi.org/10.1002/jcp.29185 Manoochehri M, Borhani N, Gerhäuser C, Assenov Y, Schönung M, Hielscher T, Christensen BC, Lee MK, Gröne HJ, Lipka DB, Brüning T, Brauch H, Ko YD, Hamann U (2023) DNA methylation biomarkers for noninvasive detection of triple-negative breast cancer using liquid biopsy. Int J Cancer 152:1025–1035. https://doi.org/10.1002/ijc.34337 Huang L, Rong Y, Tang X, Yi K, Qi P, Hou J, Liu W, He Y, Gao X, Yuan C, Wang F (2022) Engineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer. Mol Cancer 21:45. https://doi.org/10.1186/s12943-022-01515-x Xu D, Wang YL, Wang KT, Wang Y, Dong XR, Tang J, Cui YL (2021) A Scientometrics Analysis and Visualization of Depressive Disorder. Curr Neuropharmacol 19:766–786. https://doi.org/10.2174/1570159x18666200905151333 Ahmad P, Slots J (2021) A bibliometric analysis of periodontology. Periodontology 2000 85:237–240. https://doi.org/10.1111/prd.12376 Feng YX, Spezia M, Huang SF, Yuan CF, Zeng ZY, Zhang LH, Ji XJ, Liu W, Huang B, Luo WP, Liu B, Lei Y, Du S, Vuppalapati A, Luu HH, Haydon RC, He TC, Ren GS (2018) Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis 5:77–106. https://doi.org/10.1016/j.gendis.2018.05.001 Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA: A Cancer. J Clin 67:7–30. https://doi.org/10.3322/caac.21387 Kalluri R, LeBleu VS (2020) The biology, function, and biomedical applications of exosomes. Sci 367. https://doi.org/10.1126/science.aau6977 Kolovskaya OS, Zyuzyukina AV, Dassie JP, Zamay GS, Zamay TN, Boyakova NV, Khorzhevskii VA, Kirichenko DA, Lapin IN, Shchugoreva IA, Artyushenko PV, Tomilin FN, Veprintsev DV, Glazyrin YE, Minic Z, Bozhenko VK, Kudinova EA, Kiseleva YY, Krat AV, Slepov EV, Bukatin AS, Zukov RA, Shesternya PA, Berezovski MV, Giangrande PH, Kichkailo AS (2023) Monitoring of breast cancer progression via aptamer-based detection of circulating tumor cells in clinical blood samples. Front Mol Biosci 10. https://doi.org/10.3389/fmolb.2023.1184285 Abreu M, Cabezas-Sainz P, Pereira-Veiga T, Falo C, Abalo A, Morilla I, Curiel T, Cueva J, Rodríguez C, Varela-Pose V, Lago-Lestón R, Mondelo P, Palacios P, Moreno-Bueno G, Cano A, García-Caballero T, Pujana MÁ, Sánchez-Piñón L, Costa C, López R, Muinelo-Romay L (2020) Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells. Journal of Clinical Medicine 9. https://doi.org/10.3390/jcm9020353 Bidard FC, Peeters DJ, Fehm T, Nolé F, Gisbert-Criado R, Mavroudis D, Grisanti S, Generali D, Garcia-Saenz JA, Stebbing J, Caldas C, Gazzaniga P, Manso L, Zamarchi R, de Lascoiti AF, De Mattos-Arruda L, Ignatiadis M, Lebofsky R, van Laere SJ, Meier-Stiegen F, Sandri MT, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson SJ, Raimondi C, Rutten A, Janni W, Munzone E, Carañana V, Agelaki SA, Almici C, Dirix L, Solomayer EF, Zorzino L, Johannes H, Reis JS, Pantel K, Pierga JY, Michiels S (2014) Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 15:406–414. https://doi.org/10.1016/s1470-2045(14)70069-5 Fabisiewicz A, Szostakowska-Rodzos M, Zaczek AJ, Grzybowska EA (2020) Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value. Int J Mol Sci 21. https://doi.org/10.3390/ijms21051671 Chen ZH, Zeng ZH, Wan QY, Liu XH, Qi JJ, Zu YL (2022) Targeted immunotherapy of triple-negative breast cancer by aptamer-engineered NK cells. Biomaterials 280:12. https://doi.org/10.1016/j.biomaterials.2021.121259 Bryan S, Witzel I, Borgmann K, Oliveira-Ferrer L (2021) Molecular Mechanisms Associated with Brain Metastases in HER2-Positive and Triple Negative Breast Cancers. Cancers 13 https://doi.org/10.3390/cancers13164137 Taftaf R, Liu X, Singh S, Jia YZ, Dashzeveg NK, Hoffmann AD, El-Shennawy L, Ramos EK, Adorno-Cruz V, Schuster EJ, Scholten D, Patel D, Zhang YB, Davis AA, Reduzzi C, Cao Y, D'Amico P, Shen Y, Cristofanilli M, Muller WA, Varadan V, Liu HP (2021) ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer. Nat Commun 12:15. https://doi.org/10.1038/s41467-021-25189-z Stravokefalou V, Stellas D, Karaliota S, Nagy BA, Valentin A, Bergamaschi C, Dimas K, Pavlakis GN (2023) Heterodimeric IL-15 (hetIL-15) reduces circulating tumor cells and metastasis formation improving chemotherapy and surgery in 4T1 mouse model of TNBC. Front Immunol 13. https://doi.org/10.3389/fimmu.2022.1014802 Ma JL, Chen C, Fan ZM, Zhang Y, Ji JH, Wei DX, Zhang F, Sun B, Huang P, Ren LQ (2023) CircEGFR reduces the sensitivity of pirarubicin and regulates the malignant progression of triple-negative breast cancer via the miR-1299/EGFR axis. Int J Biol Macromol 244:16. https://doi.org/10.1016/j.ijbiomac.2023.125295 Lan FM, Zhang XD, Li HB, Yue X, Sun QH (2021) Serum exosomal lncRNA XIST is a potential non-invasive biomarker to diagnose recurrence of triple-negative breast cancer. J Cell Mol Med 25:7602–7607. https://doi.org/10.1111/jcmm.16009 Di Modica M, Regondi V, Sandri M, Iorio MV, Zanetti A, Tagliabue E, Casalini P, Triulzi T (2017) Breast cancer-secreted miR-939 downregulates VE-cadherin and destroys the barrier function of endothelial monolayers. Cancer Lett 384:94–100. https://doi.org/10.1016/j.canlet.2016.09.013 Yang SJ, Wang DD, Zhong SL, Chen WQ, Wang FL, Zhang J, Xu WX, Xu D, Zhang Q, Li J, Zhang HD, Hou JC, Mao L, Tang JH (2021) Tumor-derived exosomal circPSMA1 facilitates the tumorigenesis, metastasis, and migration in triple-negative breast cancer (TNBC) through miR-637/Akt1/β-catenin (cyclin D1) axis. Cell Death Dis 12:20. https://doi.org/10.1038/s41419-021-03680-1 Figueira I, Godinho-Pereira J, Galego S, Maia J, Haskó J, Molnár K, Malhó R, Costa-Silva B, Wilhelm I, Krizbai IA, Brito MA (2021) MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development. Int J Mol Sci 22:21. https://doi.org/10.3390/ijms22105214 Chaudhary P, Gibbs LD, Maji S, Lewis CM, Suzuki S, Vishwanatha JK (2020) Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis. Breast Cancer Res 22. https://doi.org/10.1186/s13058-020-1251-8 Maji S, Chaudhary P, Akopova I, Nguyen PM, Hare RJ, Gryczynski I, Vishwanatha JK (2017) Exosomal Annexin II Promotes Angiogenesis and Breast Cancer Metastasis. Mol Cancer Res 15:93–105. https://doi.org/10.1158/1541-7786.Mcr-16-0163 Jung HH, Kim JY, Lim JE, Im YH (2020) Cytokine profiling in serum-derived exosomes isolated by different methods. Sci Rep 10. https://doi.org/10.1038/s41598-020-70584-z Uslu D, Abas BI, Demirbolat GM, Cevik O (2022) Effect of platelet exosomes loaded with doxorubicin as a targeted therapy on triple-negative breast cancer cells. Mol Divers. https://doi.org/10.1007/s11030-022-10591-6 Zhao LW, Gu CY, Gan Y, Shao LL, Chen HW, Zhu HY (2020) Exosome-mediated siRNA delivery to suppress postoperative breast cancer metastasis. J Control Release 318:1–15. https://doi.org/10.1016/j.jconrel.2019.12.005 Holstege H, Joosse SA, van Oostrom CTM, Nederlof PM, de Vries A, Jonkers J (2009) High Incidence of Protein-Truncating TP53 Mutations in BRCA1-Related Breast Cancer. Cancer Res 69:3625–3633. https://doi.org/10.1158/0008-5472.Can-08-3426 Schwarzenbach H, Hoon DSB, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11:426–437. https://doi.org/10.1038/nrc3066 Riva F, Bidard FC, Houy A, Saliou A, Madic J, Rampanou A, Hego C, Milder M, Cottu P, Sablin MP, Vincent-Salomon A, Lantz O, Stern MH, Proudhon C, Pierga JY (2017) Patient -Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple -Negative Breast Cancer. Clin Chem 63:691–699. https://doi.org/10.1373/clinchem.2016.262337 Forshew T, Murtaza M, Parkinson C, Gale D, Tsui DWY, Kaper F, Dawson SJ, Piskorz AM, Jimenez-Linan M, Bentley D, Hadfield J, May AP, Caldas C, Brenton JD, Rosenfeld N (2012) Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA. Sci Transl Med 4:12. https://doi.org/10.1126/scitranslmed.3003726 Madic J, Kiialainen A, Bidard FC, Birzele F, Ramey G, Leroy Q, Frio TR, Vaucher I, Raynal V, Bernard V, Lermine A, Clausen I, Giroud N, Schmucki R, Milder M, Horn C, Spleiss O, Lantz O, Stern MH, Pierga JY, Weisser M, Lebofsky R (2015) Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients. Int J Cancer 136:2158–2165. https://doi.org/10.1002/ijc.29265 Chen YH, Hancock BA, Solzak JP, Brinza D, Scafe C, Miller KD, Radovich M (2017) Next-generation sequencing of circulating tumor DNA to predict recurrence in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy. npj Breast Cancer 3:6. https://doi.org/10.1038/s41523-017-0028-4 Pellerino A, Brastianos PK, Rudà R, Soffietti R (2021) Leptomeningeal Metastases from Solid Tumors: Recent Advances in Diagnosis and Molecular Approaches. Cancers 13:34. https://doi.org/10.3390/cancers13122888 Ortolan E, Appierto, Silvestri M, Miceli R, Veneroni S, Folli S, Pruneri G, Vingiani A, Belfiore A, Cappelletti, Vismara M, Dell'Angelo F, De Cecco L, Bianchi G, de Braud FG, Daidone MG, Di Cosimo S (2021) Blood-based genomics of triple-negative breast cancer progression in patients treated with neoadjuvant chemotherapy. ESMO Open 6:10. https://doi.org/10.1016/j.esmoop.2021.100086 Cavallone L, Aguilar-Mahecha A, Lafleur J, Brousse S, Aldamry M, Roseshter T, Lan C, Alirezaie N, Bareke E, Majewski J, Ferrario C, Hassan S, Discepola F, Seguin C, Mihalcioiu C, Marcus EA, Robidoux A, Roy JA, Pelmus M, Basik M (2020) Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer. Sci Rep 10:13. https://doi.org/10.1038/s41598-020-71236-y Kim H, Kim YJ, Park D, Park WY, Choi DH, Park W, Cho WK, Kim N (2021) Dynamics of circulating tumor DNA during postoperative radiotherapy in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: a prospective observational study. Breast Cancer Res Treat 189:167–175. https://doi.org/10.1007/s10549-021-06296-3 Foulkes WD, Smith IE, Reis JS (2010) Triple-Negative Breast Cancer. N. Engl. J Med 363:1938–1948. https://doi.org/10.1056/NEJMra1001389 Pascual J, Lim JSJ, Macpherson IR, Armstrong AC, Ring A, Okines AFC, Cutts RJ, Herrera-Abreu MT, Garcia-Murillas I, Pearson A, Hrebien S, Gevensleben H, Proszek PZ, Hubank M, Hills M, King J, Parmar M, Prout T, Finneran L, Malia J, Swales KE, Ruddle R, Raynaud FI, Turner A, Hall E, Yap TA, Lopez JS, Turner NC (2021) Triplet Therapy with Palbociclib, Taselisib, and fulvestrant in PIK3CA-Mutant Breast Cancer and Doublet Palbociclib and Taselisib in Pathway-Mutant Solid Cancers. Cancer Discov 11:92–107. https://doi.org/10.1158/2159-8290.Cd-20-0553 Sukumar J, Gast K, Quiroga D, Lustberg M, Williams N (2021) Triple-negative breast cancer: promising prognostic biomarkers currently in development. Expert Rev Anticancer Ther 21:135–148. https://doi.org/10.1080/14737140.2021.1840984 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4203189","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":286615028,"identity":"94e52980-41ed-4e08-bb16-bb7e9f1bf921","order_by":0,"name":"Yi Qu","email":"","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Qu","suffix":""},{"id":286615029,"identity":"5f598224-5a23-48b7-af15-8a57f57ea399","order_by":1,"name":"Jixian Wan","email":"","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Jixian","middleName":"","lastName":"Wan","suffix":""},{"id":286615030,"identity":"fb645e9c-1360-47e2-b531-ff137e57f102","order_by":2,"name":"Ruihan Li","email":"","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Ruihan","middleName":"","lastName":"Li","suffix":""},{"id":286615031,"identity":"e5da1259-3c2b-4da5-b3a9-fd151347ffe0","order_by":3,"name":"Xinyuan Li","email":"","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Xinyuan","middleName":"","lastName":"Li","suffix":""},{"id":286615032,"identity":"cc88fc14-14d8-45f2-aacb-2fc0b84ca931","order_by":4,"name":"Han Li","email":"","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Han","middleName":"","lastName":"Li","suffix":""},{"id":286615033,"identity":"e8adbee8-2d38-4022-831e-45fc2b6af5d0","order_by":5,"name":"Yang Li","email":"","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Yang","middleName":"","lastName":"Li","suffix":""},{"id":286615034,"identity":"6459be90-6fa0-4331-aa59-676bd04eac29","order_by":6,"name":"Shengnan Huang","email":"","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Shengnan","middleName":"","lastName":"Huang","suffix":""},{"id":286615035,"identity":"57548e7a-52d4-45c8-bb66-85fa0c9795b5","order_by":7,"name":"Tingting Zhang","email":"","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Tingting","middleName":"","lastName":"Zhang","suffix":""},{"id":286615036,"identity":"9b5091ae-7a56-4183-a442-8433bf006a39","order_by":8,"name":"Dawei Yang","email":"","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":false,"prefix":"","firstName":"Dawei","middleName":"","lastName":"Yang","suffix":""},{"id":286615037,"identity":"32468155-3a43-4890-9ce1-03c49d1e4bf2","order_by":9,"name":"Dongliang Chen","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1UlEQVRIie3PoQ7CMBCA4SNLOlM25BoIz1AMGBJeZVUoEuTEBGSkE8AD8BbISUiTDVH85Gbm50AQKIEgt0pEf3Mn7hMHYDL9Yxmg98CuvV4XfhBqEPEhA7ITES1kqk+mNJ9zUm6sduEIqyrqBDDNGQ/YCoEbb/1GQgSajA4SMJElz1kyAE9ej42ECoz6XQ7YyZgiEgH1FhrkoQicGF8ybmmSjiK9C+OgRdQvY7JXhOzOkefLFLf+4mRR5d05zFw7LutbEA7deN9Mvj1/G9Y5N5lMJlNLLyO2SILKWu5ZAAAAAElFTkSuQmCC","orcid":"","institution":"Zhong Yuan Academy of Biological Medicine, Liaocheng People’s Hospital","correspondingAuthor":true,"prefix":"","firstName":"Dongliang","middleName":"","lastName":"Chen","suffix":""}],"badges":[],"createdAt":"2024-04-02 01:44:37","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4203189/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4203189/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":54160290,"identity":"ac50c3d1-2ddb-4a49-9fdf-b99c885ae880","added_by":"auto","created_at":"2024-04-05 12:57:30","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":209351,"visible":true,"origin":"","legend":"\u003cp\u003eOverview of the paper's logical framework\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/dc9f3728e4238b918bf312dc.png"},{"id":54160334,"identity":"c482b275-e4b4-4ab3-9c89-b396da2d1fc6","added_by":"auto","created_at":"2024-04-05 12:57:35","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":195335,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart illustrating the data cleansing strategy. Arrows denote the sequential order of cleansing, while the headings in the right column represent the filtering criteria\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/90dba1b7b8eeca03ae0e4c1a.png"},{"id":54160317,"identity":"101c6b13-f0b9-4321-9e07-55088f86f365","added_by":"auto","created_at":"2024-04-05 12:57:34","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":162246,"visible":true,"origin":"","legend":"\u003cp\u003eAnnual variation in the number of published literature\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/519c17fe48b434b8740b8f96.png"},{"id":54160293,"identity":"e680ea08-b8b0-4647-8329-48383ab9ebd0","added_by":"auto","created_at":"2024-04-05 12:57:32","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":274844,"visible":true,"origin":"","legend":"\u003cp\u003eWorldwide distribution of documents on TNBC\u003c/p\u003e","description":"","filename":"Fig.4.png","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/e264cbf516ca67d9c2b0394d.png"},{"id":54160289,"identity":"75598bea-87d0-46ea-8dfb-e9833fef1e1a","added_by":"auto","created_at":"2024-04-05 12:57:30","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":485863,"visible":true,"origin":"","legend":"\u003cp\u003eCo-citation analysis of literature\u003c/p\u003e","description":"","filename":"Fig.5.png","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/7899dfeaac0a02d3fdea090b.png"},{"id":54160297,"identity":"e8332230-f0af-41c8-9823-7491a7d33371","added_by":"auto","created_at":"2024-04-05 12:57:33","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":510580,"visible":true,"origin":"","legend":"\u003cp\u003eCoupling of relevant literature on liquid biopsy applications in TNBC\u003c/p\u003e","description":"","filename":"Fig.6.png","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/31b8541c9689e7d000a71215.png"},{"id":54160295,"identity":"e6453b43-e3ed-476d-b512-1ea2b59f1933","added_by":"auto","created_at":"2024-04-05 12:57:33","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":139784,"visible":true,"origin":"","legend":"\u003cp\u003eHeat map of journal publications\u003c/p\u003e","description":"","filename":"Fig.7.png","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/f46b5c3d8bbfe4741b3cf6ff.png"},{"id":54160315,"identity":"a58e83cf-4404-4e6a-bd8d-66fbb1efad2c","added_by":"auto","created_at":"2024-04-05 12:57:34","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":693224,"visible":true,"origin":"","legend":"\u003cp\u003eKeyword timeline graph\u003c/p\u003e","description":"","filename":"Fig.8.png","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/1ffb18ba962cb0acb4ebf886.png"},{"id":54160296,"identity":"8a2ec2b8-8141-495d-b9fc-d20aeb56f597","added_by":"auto","created_at":"2024-04-05 12:57:33","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":300447,"visible":true,"origin":"","legend":"\u003cp\u003eTop 25 keywords with the Strongest Citation Brusts\u003c/p\u003e","description":"","filename":"Fig.9.png","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/0119564aeffdc3867936c1e1.png"},{"id":54435719,"identity":"e2343a84-a3fb-404c-9e94-37234789bb1b","added_by":"auto","created_at":"2024-04-10 13:14:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3488935,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4203189/v1/84cff036-9013-47da-ab99-dd698449cdf3.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Research History, Current Trends, and Future Prospects of Liquid Biopsy in Triple-Negative Breast Cancer: An Analysis from a Global Perspective","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eBreast cancer, recognized as the most frequently diagnosed malignancy in women, displays significant diversity across histologic classification, etiology, pathogenesis, clinical manifestation, therapeutic modalities, and treatment outcomes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Among its various subtypes, triple-negative breast cancer (TNBC) accounts for approximately 15\u0026ndash;20 percent. Distinguished by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER-2), TNBC emerges as a remarkably heterogeneous disease. TNBC manifests aggressively, disproportionately affecting women in younger and premenopausal age groups [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Consequently, previous studies have indicated that TNBC has a worse prognosis compared to other breast cancer subtypes, leading to lower survival rates for patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCurrently, the absence of early diagnostic markers for TNBC poses a significant challenge, with percutaneous transluminal biopsy serving as the gold standard but encountering key limitations. Therefore, there exists an urgent need for new methods facilitating early TNBC diagnosis [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. In contrast to tissue biopsy, liquid biopsy presents numerous advantages, including non-invasiveness, ease of operation, reduced risk, detection of minute lesions, and comprehensive tumor profiling. As such, attention has shifted towards liquid biopsy as a promising alternative. Liquid biopsy, a non-invasive technique used for tumor detection, retrieves tumor-related information through the analysis of body fluids such as blood, urine, and ascites. Notably, it has demonstrated successful applications in detecting multiple cancer types, including TNBC [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. This study aimed to use literature visualisation to elucidate research hotspots and provide novel insights into the application of liquid biopsy in TNBC.\u003c/p\u003e \u003cp\u003eBibliometrics is one of the most important methods for literature visualisation, having previously played an important role in hotspot mining across a wide range of solid tumors, including lung cancer and endometrial cancer [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. As an interdisciplinary science of quantitative analysis of knowledge carriers, bibliometrics primarily measures the number of documents (particularly journal papers and citations), the number of authors (individual or groups), and the number of words (document identifiers, mostly descriptors). Using software tools to analyse relevant literature, this paper provides an intuitive and comprehensive overview for researchers, summarizing current hotspots and addressing existing challenges to provide directions for future research (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"2. Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Sources of data and search strategies\u003c/h2\u003e \u003cp\u003eBibliometric analysis was conducted using the Web of Science (Clarivate Analytics). To mitigate potential deviations due to rapid database updates, literature retrieval was completed within a single day on 3 January 2024. Search terms were refined using Medical Subject Headings as follows: ((TS=(liquid-biopsy) OR TS=(fluid-biopsy) OR TS=(circulating-tumo*-cell*) OR TS=(CTC*) OR TS= (cell-free-tumo*- DNA*) OR TS=(cfDNA*) OR TS=(ctDNA*) OR TS=(circulating-tumo*-DNA*) OR TS=(exosome*)) AND (TS= (triple-negative-breast-cancer*) OR TS=( triple-negative-breast- Neoplasm*))). Only original articles and reviews written in English were considered among various publication types. Two researchers (QY and LRH) independently searched raw data and subsequently discussed any discrepancies, resulting in a final concordance of 0.87, indicating substantive consistency.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data Collection and Cleaning\u003c/h2\u003e \u003cp\u003eInitially, a search was performed in Web of Science (Clarivate Analytics) using search terms limited to original articles and reviews written in English. Subsequently, the \"full record with cited references\" of all retrieved publications was exported. Finally, the resulting data were imported into bibliometric analysis software for subsequent analysis and visualization. A detailed data cleansing strategy is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"3. Result","content":"\u003cp\u003eComprehensively understanding the field of liquid biopsy in TNBC and staying updated with the latest research poses increasing challenges due to rapidly evolving technology. To gain an overview of global trends regarding the use of liquid biopsy in TNBC, bibliometric analysis was used to visualise and analyse data about countries, journals, literature co-citations, couplings, timeline graphs, and emergent terms along a temporal axis, spanning historical trends, current hotspots, to future directions.\u003c/p\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e3.1 Overview\u003c/h2\u003e \u003cp\u003eA total of 347 papers were included in this study, including 286 original articles (82.4%) and 61 review papers (17.6%). The number of publications was fitted using the model: y\u0026thinsp;=\u0026thinsp;y\u003csub\u003e0\u003c/sub\u003e\u0026thinsp;+\u0026thinsp;A\u003csub\u003e1\u003c/sub\u003e*exp((x-x\u003csub\u003e0\u003c/sub\u003e)/t\u003csub\u003e1\u003c/sub\u003e), with the fitting results displayed in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The figure summarises the fluctuation in the number of publications between 2012 and 2023. Additionally, a curve was fitted using a model where the dark red band represents the 95% confidence band of the fitted curve, and the light red band depicts the 95% prediction zone of the fitted curve.\u003c/p\u003e \u003cp\u003eThe fitting results suggest a rapid development stage in the field, with a projected increase to 160 related papers by 2025.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e3.2 Integration and comparison of global cooperation networks\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTop 10 countries according to publications\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCountry\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003epublications\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCitations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal link strength(TLS)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAverage Citation/Document\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUSA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e130\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4863\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e81\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e37.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChina\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e104\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3150\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e30.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGermany\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e710\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e25.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eItaly\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e815\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e31.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIndia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e562\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e29.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSouth Korea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e342\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e21.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited Kingdom\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e368\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e26.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJapan\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e232\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAustralia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e171\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e14.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCanada\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e181\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e15.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eA total of 23 eligible countries with a minimum of 4 documents were screened.The TNBC multi-country collaborative network is illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, in which circle sizes represent the number of documents, while the thickness of the line indicates the degree of connectivity for each country. We can found that China and the USA forming the initial collaborative network. The USA leads in publications and has the most collaborating countries, particularly with China. China ranks second in publications but exhibits low total link strength (TLS). The top 10 countries, ranked by the number of published papers, are listed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, with the USA (130, 28.0%) in the first place, followed by China (104, 22.6%), and Germany (28, 6.1%). Notably, both the USA and China have over 100 publications, indicating their leadership in triple-negative liquid biopsy research. Furthermore, total link strength with other countries is calculated, with the USA (TLS: 81) leading, followed closely by Germany (TLS: 31), and China (TLS: 30).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e3.3 Mining and summarisation of hot publications\u003c/h2\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTop 10 publications by total citations\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTitle\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eDOI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal Citations\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eTC per Year\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNormalized TC\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eBreast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.gendis.2018.05.001\u003c/span\u003e\u003cspan address=\"10.1016/j.gendis.2018.05.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e506\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e72.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e5.67\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHypoxia-inducible factors and RAB22A mediate formation of microvesicles that stimulate breast cancer invasion and metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1073/pnas.1410041111\u003c/span\u003e\u003cspan address=\"10.1073/pnas.1410041111\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e351\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.27\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMetastatic and triple-negative breast cancer: challenges and treatment options\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s13346-018-0551-3\u003c/span\u003e\u003cspan address=\"10.1007/s13346-018-0551-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e306\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.43\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTumor microenvironment: Challenges and opportunities in targeting metastasis of triple negative breast cancer\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.phrs.2020.104683\u003c/span\u003e\u003cspan address=\"10.1016/j.phrs.2020.104683\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e220\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.94\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHomophilic CD44 Interactions Mediate Tumor Cell Aggregation and Polyclonal Metastasis in Patient-Derived Breast Cancer Models\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1158/2159-8290.CD-18-0065\u003c/span\u003e\u003cspan address=\"10.1158/2159-8290.CD-18-0065\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.24\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExosome-mediated siRNA delivery to suppress postoperative breast cancer metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jconrel.2019.12.005\u003c/span\u003e\u003cspan address=\"10.1016/j.jconrel.2019.12.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e204\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e40.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e4.58\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003emiR-134 in extracellular vesicles reduces triple-negative breast cancer aggression and increases drug sensitivity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.18632/oncotarget.5192\u003c/span\u003e\u003cspan address=\"10.18632/oncotarget.5192\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTargeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/cas.14181\u003c/span\u003e\u003cspan address=\"10.1111/cas.14181\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e183\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFunctional exosome-mediated co-delivery of doxorubicin and hydrophobically modified microRNA 159 for triple-negative breast cancer therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12951-019-0526-7\u003c/span\u003e\u003cspan address=\"10.1186/s12951-019-0526-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e180\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e3.48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eExosomes from triple-negative breast cancer cells can transfer phenotypic traits representing their cells of origin to secondary cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ejca.2013.01.017\u003c/span\u003e\u003cspan address=\"10.1016/j.ejca.2013.01.017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e2.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e presents the top 10 highly cited publications relevant to the analysis. The most cited document titled \"Breast cancer development and progression: risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis\" summarizes a total of 373 papers discussing risk factors, common mutation sites, classification and early symptoms, molecular subtypes, available targeted therapies, clinical staging, and survival in breast cancer fundamental issues [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eA total of 21 co-citations were analysed with a minimum threshold of 20 citations for co-cited literature, resulting in the grouping of these citations into three clusters (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e).Circles represent the more cited literature, with the size of the circle indicating the number of citations. Different colors represent different clusters, and each cluster of cited literature has the same focus, which is marked on the side.\u003c/p\u003e \u003cp\u003eThe first cluster, marked in red, focuses on targeted therapies for different subtypes of TNBC. This indicates that targeted therapies and related targeted therapeutic agents are currently a prominent research topic. The second cluster, highlighted in green, emphasizes the potential of CTCs and liquid biopsy in the detection and prognosis of TNBC. Lastly, the third cluster, denoted in blue, indicates the application of exosomes as biomarkers and therapeutic targets in TNBC research.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTop 10 coupled literature by centrality\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCenterity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eYear\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCited References\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2017\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSiegel RL, 2017, CA-CANCER J CLIN, V67, P7, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3322/caac.21387\u003c/span\u003e\u003cspan address=\"10.3322/caac.21387\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDawson SJ, 2013, NEW ENGL J MED, V368, P1199, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1056/NEJMoa1213261\u003c/span\u003e\u003cspan address=\"10.1056/NEJMoa1213261\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eYu MY, 2019, CANCER SCI, V110, P3173, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1111/cas.14181\u003c/span\u003e\u003cspan address=\"10.1111/cas.14181\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLehmann BD, 2011, J CLIN INVEST, V121, P2750, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1172/JCI45014\u003c/span\u003e\u003cspan address=\"10.1172/JCI45014\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eGarcia-Murillas I, 2019, JAMA ONCOL, V5, P1473, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1001/jamaoncol.2019.1838\u003c/span\u003e\u003cspan address=\"10.1001/jamaoncol.2019.1838\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMadic J, 2015, INT J CANCER, V136, P2158, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/ijc.29265\u003c/span\u003e\u003cspan address=\"10.1002/ijc.29265\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCarey L, 2010, NAT REV CLIN ONCOL, V7, P683, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/nrclinonc.2010.154\u003c/span\u003e\u003cspan address=\"10.1038/nrclinonc.2010.154\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eStevic I, 2018, BMC MED, V16, P0, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12916-018-1163-y\u003c/span\u003e\u003cspan address=\"10.1186/s12916-018-1163-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2014\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBidard FC, 2014, LANCET ONCOL, V15, P406, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/S1470-2045(14)70069-5\u003c/span\u003e\u003cspan address=\"10.1016/S1470-2045(14)70069-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2018\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLi YM, 2018, CELL DEATH DIS, V9, P0, DOI \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1038/s41419-017-0030-7\u003c/span\u003e\u003cspan address=\"10.1038/s41419-017-0030-7\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e shows a trend of increasing concentration and heightened centrality of couplings increases over time. The top 10 coupled literatures, ranked by centrality, are listed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. The most centrally coupled literature is \u0026ldquo;Cancer Statistics, 2017\u0026rdquo; demonstrating its comprehensive and fundamental nature [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This literature not only presents statistical evidence of a consistent decline in cancer mortality over the past 20 years but also predicts a reduction in racial disparities impacting cancer mortality. Thus, its comprehensiveness provides a basis for future research.\u003c/p\u003e \u003cp\u003eRanked third, \u0026ldquo;Targeted exosome-encapsulated erastin induced ferroptosis in triple negative breast cancer cells\u0026rdquo;, exhibits significant coupling centrality despite its later publication, suggesting seminal findings and a strong impact. Notably, the literature, \u0026ldquo;The biology, function, and biomedical applications of exosomes\u0026rdquo; published in 2020, although ranked 16th, displayed the highest coupling centrality among recent publications [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Tracking and analyses of high-level journals\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eJournals with the highest number of publications are represented in different colour blocks, with shades of yellow indicating a greater number of publications for that year (Fig.\u0026nbsp;\u003cspan refid=\"Fig7\" class=\"InternalRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe heatmap reveals a significant increase in liquid biopsy literature starting from 2020. \u003cem\u003eBMC Cancer\u003c/em\u003e stands out with a consistently high volume of publications, suggesting ongoing engagement with pertinent research in the field since 2020. Meanwhile, \u003cem\u003eClinical Cancer Research\u003c/em\u003e demonstrates the longest duration of publication activity, spanning multiple years.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTop 10 journals by publication frequency\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRank\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSources\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePublications\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLocal Cited(LC)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eAverage LC/Document\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIF\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eCancers\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e234\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eInternational Journal of Molecular Sciences\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eBreast Cancer Research\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e354\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eBreast Cancer Research and Treatment\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e352\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eClinical Cancer Research\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e628\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e78.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.5\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eFrontiers in Oncology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.2\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eScientific Reports\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e282\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eCancer Letters\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e155\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e25.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eFrontiers in Immunology\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003eBMC Cancer\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIn Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e, \u003cem\u003eCancers\u003c/em\u003e leads with 16 publications and an Impact Factor (IF) of 5.6, focusing on TNBC cancer and CTCs. Following closely is the \u003cem\u003eInternational Journal of Molecular Sciences\u003c/em\u003e with 12 publications and an IF of 6.2, focusing on exosomes, ctDNA, etc. Approximately 24% of the literature reviewed originated from these top 10 academic journals (83/23.9%). Notably, all of these top ten journals have a high IF greater than 3.0, indicating their significant impact over the past twelve years. \u003cem\u003eClinical Cancer Research\u003c/em\u003e stands out with the highest IF of 12.5 and the highest citation rate.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e3.5 Summary and organisation of keywords\u003c/h2\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e, the primary keywords in the field are presented in a timeline graph. The size of each circle represents the frequency of occurrence of the keyword, and its position in the center of the circle indicates the timing of its first appearance. Keywords are divided into clusters based on their co-occurrence strength, with separate clusters displayed on the right side. Keywords are categorized into 9 clusters according to their link strength. Notably, liquid biopsy-associated molecules associated with metastasis in TNBC are highlighted in cluster #0 labelled \"metastasis\". Exosomes are highlighted in the timeline plot, demonstrating that they are most strongly associated with TNBC metastasis. Additionally, \"circulating tumor cells\" in Cluster #1 and the \"cell-free DNA\" in Cluster #5 are both associated with \"liquid biopsy\" in Cluster #2. \"Triple-negative breast cancer\" in Cluster #3 is strongly associated with the \"androgen receptor\" in Cluster #4. Cluster #6, \"nanoparticles\", around 2019, introduces \"nanoparticles,\" underscoring the deep intersection of nanotechnology with the medical field. Cluster #7 and Cluster #8 primarily focus on drug therapy for TNBC.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eIn Fig.\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e, the top 25 words ranked by intensity over time are presented. The length of the red line segments indicates the duration of the burst word's sudden appearance. Among these \"phage ii\" (4.08: Strength), \"TNBC\" (3.00: Strength), and \"substage\" (2.51: Strength) are the most intense during 2019 and 2020. Particularly noteworthy is the emphasis on the phage ii stage, a key point of the study. Starting in 2022, buzzwords such as \"promotes\", \"poor prognosis\" and \"biomarkers\" have emerged and continued to gain significance.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Review of research history\u003c/h2\u003e \u003cp\u003eThis study used a bibliometric analysis approach to systematically review 347 papers published between 2012 and 2023, aiming to provide insights into important publication trends, explore collaborative efforts among researchers, and anticipate future perspectives in the field.\u003c/p\u003e \u003cp\u003eThe initial step involved analyzing the number of literature references, followed by the fitting of growth curves to record and predict the expansion of literature. The growth curve exhibits a seemingly exponential form, indicating a growing interest and appreciation for the field among researchers in recent years. At the country level, the USA ranks first, followed by China. Additionally, the USA demonstrates close collaborations with global countries, fostering a diverse cooperation network, a model worthy of emulation by other nations. Beyond political and geographical factors, the USA\u0026rsquo;s reputable academic environment, strong financial resources, and leading modern scientific foundation likely attract collaboration and foster multi-sourced research outcomes. However, despite Germany\u0026rsquo;s high publication count, its citation average falls short, signaling a need to prioritize quality over quantity in research endeavors.\u003c/p\u003e \u003cp\u003eIn terms of literature content, the most cited studies focus on breast stem cells, tumor heterogeneity, cell signaling, epigenetics, and non-coding RNAs, offering researchers a comprehensive understanding of TNBC [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Visual representation of literature co-citations in three clusters improves accuracy in understanding their interconnections. Subsequently, we analyzed the publication heat of journals hosting this literature. Post-2020, many listed journals experienced a significant increase in publication heat, with \u003cem\u003eBMC Cancer\u003c/em\u003e consistently maintaining the highest level. Notably, \u003cem\u003eClinical Cancer Research\u003c/em\u003e not only has the highest IF but also the largest number of citations. The journal was the first to publish a study on the application of liquid biopsy in TNBC, specifically a phase I clinical trial evaluating the efficacy of veriparib in combination with beat cyclophosphamide for solid tumor treatment.\u003c/p\u003e \u003cp\u003eAt the keyword level, expressed through timeline graphs and emergent word analyze, studies applying liquid biopsy in TNBC have progressively deepened since 2012. Initially, the focus of liquid biopsy research in TNBC was mainly on early diagnosis. Currently research focus is shifting towards evaluating the therapeutic effectiveness and predicting the prognosis of TNBC,, particularly evident from 2021 onwards.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Summary and discussion of popular themes\u003c/h2\u003e \u003cp\u003eThis study presents a comprehensive literature review of liquid biopsy application in TNBC on a temporal axis, integrating visual analysis results to outline major research. Systematically reviewing progress across CTCs, exosomes, and ctDNA branches, we summarize current findings, including the latest diagnostic approaches, and treatment strategyies. These findings aim to assist researchers in navigating current research hotspots and accessing the latest outcomes.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section3\"\u003e \u003ch2\u003e4.2.1 Discussion on circulating tumor cells (CTCs)\u003c/h2\u003e \u003cp\u003eThe most cited publications \"Breast cancer development and progression: risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis\" highlighted the positive role of blood CTCs in tumourigenesis, with proteomic and genomic analyses informing the basis for further target studies. The potential of CTCs as a biomarker is highlighted in the green cluster in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e. Consequently, key themes in the CTCs branch, such as \"biomarkers\", \"targets\", \"biomodels\" and \"immunotherapeutic inhibitors\" are identified.\u003c/p\u003e \u003cp\u003eThe migratory properties of CTC present opportunities for enhancing early diagnosis, refining therapeutic approaches through specific target or biomarker identification, and providing prognostic value, including predicting the likelihood of recurrence [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Studies based on liquid biopsy techniques have explored multiple factors contributing to the spread of TNBC tumors. Importantly, CTCs in TNBC patients exhibit plasticity. For example, research has observed an upregulation in the expression of CTC genes that promote TNBC proliferation. This finding suggests the potential use of CTCs as novel targets for early diagnosis and therapeutic interventions [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eClinically, evaluating the number and molecular characteristics of CTCs in early-stage breast cancer patients can provide important tumor information, which is more accurate, timely, and relevant than primary tumor tissue analysis obtained through surgery. This provides new ideas for individualised treatment and may significantly impact clinical decision-making [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTherapeutically, the single-stranded DNA aptamer (PDGC21-T) demonstrates remarkable selectivity towards TNBC cell lines [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. This breakthrough opens avenues for innovation and enhancement of immunotherapy, promising improved efficacy.\u003c/p\u003e \u003cp\u003eRecent literature analysis in the field of CTCs reveals that current research is focused on novel approaches to prevent or stop metastases in advanced breast cancer by influencing CTCs formation and survival through relevant signalling pathways. This suggests potential areas for future complementary therapies and improved prognosis [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. Recent studies suggest that anti-ICAM1 neutralising antibodies may prevent TNBC cell aggregation and reduce metastasis occurrence [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Meanwhile, the discovery of the anti-metastatic effect of hetIL-15 provides a new complementary solution based on its combination with a post-surgical doxorubicin treatment regimen [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section3\"\u003e \u003ch2\u003e4.2.2 Discussion on exosomes\u003c/h2\u003e \u003cp\u003eThe blue cluster in Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e, emphasising exosomes, underscores their potential as biomarkers and alternative therapeutic approaches. The diagnostic role of exosomes in TNBC primarily relies on exosome-derived RNAs.Variations in the levels of various RNAs in exosomes have been found to be associated with the development of TNBC, including lncRNA XIST, circRNA circPSMA1, circEGFR, circHIF1A, BATF2 mRNA, miR-939, miR-194-5p, miR-205-5p, etc [\u003cspan additionalcitationids=\"CR22 CR23 CR24\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAdditionally, with the development of proteomics, the diagnostic potential of proteins in exosomes has been extensively studied [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Previous studies have found a 36kDa calcium-dependent phospholipid-binding protein, annexin A2 (AnxA2), as highly expressed in the exosomes of TNBC patients. This highlights the potential diagnostic significance of exosome-associated proteins, such as AnxA2, in the context of TNBC [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. Simultaneously, a notable disparity in the expression of exosomal annexin A2 (exo-AnxA2) was observed among breast cancer cells of different natures, underscoring the potential of exo-AnxA2 as a biomarker for breast cancer [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Moreover, Jung H H et al. found significant alterations in the concentration of MIP-3α and other proteins in exosomes from metastatic breast cancer patients. However, due to the small sample size, these findings do not conclusively reflect breast cancer disease progression and require validation in future studies [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExosomes serve various biological functions, including mediating cell communication, immunomodulation, anti-inflammation, and promoting angiogenesis.\u003c/p\u003e \u003cp\u003eTherapeutically, leveraging exosomes as a tool for TNBC treatment is a feasible approach. In Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e, Cluster #6 highlights the potential of exosomes as nanocarriers for drug delivery. Their optimal size can prevent removal by phagocytosis, and their excellent biocompatibility minimizes cytotoxic effects and immunogenicity. Exosomes can be used as delivery agents for molecular drugs and can be categorized into two drug-carrying pathways based on the difference in the way of loading drugs, 1) endogenous drug-carrying pathway 2) exogenous drug-carrying pathway. Endogenous drug loading pathway is based on the engineering loading method of parental cells, and the exosome-derived cells are modified; exogenous drug loading pathway is to load drugs directly into exosomes through membrane penetration and other strategies. In general, the exogenous loading route is more efficient. Dilara Uslu et al. demonstrated successful targeting of TNBC using doxorubicin (DOX)-loaded platelet exosomes [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Furthermore, a team of researchers has developed new exosome-delivered drugs, CBSA/siS100A4@Exosome nanoparticles, utilizing exosome-loaded cationic bovine serum albumin (CBSA) conjugated with siS100A4, effectively inhibiting distant metastasis in TNBC, particularly lung metastasis [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eFigure\u0026nbsp;\u003cspan refid=\"Fig9\" class=\"InternalRef\"\u003e9\u003c/span\u003e, several key words related to prognostic value, such as \"survival\" and \"poor prognosis,\" highlight the current research focus in the liquid biopsy field. Previous studies have indicated that changes in exosomal contents can serve as indicators of tumor drug resistance. In 2023, Jiulong Ma et al. demonstrated that circRNA EGFR was highly expressed in TNBC cell lines, patient tissues, and plasma exosomes, correlating with piroxicam resistance in patients. This impact was mediated through the circEGFR/miR-1299/EGFR pathway. Silencing circEGFR rendered patients more sensitive to piroxicam, leading to an improved prognosis. This underscores the prognostic, predictive, and therapeutic value of exosomes [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e4.2.3 Discussion on circulating tumor DNA (ctDNA)\u003c/h2\u003e \u003cp\u003eShown in Fig.\u0026nbsp;\u003cspan refid=\"Fig8\" class=\"InternalRef\"\u003e8\u003c/span\u003e, ctDNA is the main cluster of TNBC liquid biopsy. The primary mutation site in TNBC is \u003cem\u003eTP53\u003c/em\u003e, which plays a pivotal role in driving tumor cell development; followed by \u003cem\u003ePIK3CA\u003c/em\u003e [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. Released into the circulatory system by tumor cells, ctDNA serves as a non-invasive liquid biopsy and an emerging biomarker for circulating tumors [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. Riva. F et al. demonstrated a significant correlation between ctDNA levels and clinical tumor size (continuous variable, P\u0026thinsp;\u0026lt;\u0026thinsp;0.004), tumor stage (P\u0026thinsp;\u0026lt;\u0026thinsp;0.03), and high value-added rate, i.e., tumor load [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Next-Generation Sequencing (NGS) has shown high consistency in detecting ctDNA [\u003cspan additionalcitationids=\"CR35\" citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eClinically, Pellerino.A et al. found that ctDNA can identify targeted mutations in metastatic breast cancer and diagnose early metastatic leptomeningeal disease, although substantial data from cerebrospinal fluid liquid biopsy are needed [\u003cspan citationid=\"CR37\" class=\"CitationRef\"\u003e37\u003c/span\u003e]. Prospective trials suggest that patients remaining positive for ctDNA after surgery following neoadjuvant chemotherapy (NAC) have an increased risk of recurrence compared to those with undetectable ctDNA, inspiring prognostic predictions based on this characteristic [\u003cspan additionalcitationids=\"CR39\" citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eTherapeutically, in the absence of distant metastasis, TNBC is typically treated with neoadjuvant chemotherapy (NCT) to reduce tumor size, followed by surgery [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Notably, TNBC patients often achieve a high rate of pathological complete response (pCR) after NCT compared to other types of breast cancer [\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBy reviewing recent literature, it is concluded that ctDNA can serve as an indicator for assessing tumor evolution, and early kinetic testing of ctDNA can replace other assessments [\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e, \u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]. Early screening for breast cancer is crucial for therapeutic outcomes. Therefore, more advanced technology is needed to screen for trace amounts of ctDNA in early body fluids, providing more patients with early-stage breast cancer a chance for a cure. Moreover, there is potential for more personalised therapies targeting the breast immune microenvironment [\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThis paper pioneers the use of bibliometrics to analyze the application of liquid biopsy in TNBC. Through bibliometric analysis, we conducted in-depth profiling mining. The fitted curve, based on the growth in the number of publications over time, suggests significant potential and promise in this area. Visual graphs illustrate that the USA and China have been leaders in TNBC-related liquid biopsy research, with the USA having the highest influence. Journals with the highest publication rates were identified; with \u003cem\u003eClinical Cancer Research\u003c/em\u003e having the longest span of publications. Literature co-citation analysis reveals a focus on subtypes, cell models, and targeted therapies. An analysis of keywords indicates a previous focus on sensitive targets and the nano-field. The evolution of keywords over time demonstrates a shift in focus from mechanism to diagnosis, immunotherapy, and prognosis. In summary, this study objectively and comprehensively demonstrates the research dynamics, hotspots, frontiers, problems, and deficiencies in the field of TNBC-related liquid biopsy through bibliometric analysis. It aims to assist scholars in identifying strengths and weaknesses in this field to enrich and improve its development.\u003c/p\u003e"},{"header":"6. Limitations","content":"\u003cp\u003eTo address potential subjective influences arising from merging databases, this study exclusively collected data from a single database, Web of Science. However, this approach may introduce errors in data collection. Despite using the MeSH word list to optimize the search formula for accuracy, there is inevitably some missing data in this study. While the data in this study were independently collected and cleaned by two researchers, the possibility of subjective bias still exists.\u003c/p\u003e \u003cp\u003eIn keyword analysis, attempts were made to merge synonyms; however, there may be instances where related words were not merged. Measures have been taken to minimize the impact of unmerged keywords on the final results.\u003c/p\u003e"},{"header":"7. Innovations","content":"\u003cp\u003eLiquid biopsy-associated molecules in TNBC have undergone extensive studies. Bibliometrics offers objective classification indexes, thereby minimizing subjective factors. In this study, we analyzed all publications from WoS in related fields, revealing the countries of affiliation and journals of publication for each. Visualization tools were employed to intuitively display collaboration networks and research focus, guiding the direction of subsequent research. This study represents the first to utilize bibliometrics to analyze the application of liquid biopsy in TNBC.\u003c/p\u003e \u003cp\u003eAdditionally, the objective analysis of keywords is another notable aspect of this paper. By utilizing a timeline diagram to visualize the evolution of the field and burst words, the paper scrutinizes both past and current research hotspots while predicting possible future research directions.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was supported by the Natural Science Foundation of Shandong Province of China (ZR2021MH215), the Liaocheng Key R\u0026amp;D Plan (2022YDSF37 and 2023YD22), and the Science and Technology Development Project of the Affiliated Hospital of Weifang Medical College (2023FYQ034 and 2023FYM105).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicting of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no potential conflicts of interest with respect to the research, authorship, and publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData Availability\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study used data from the Web of Science Core Collection database.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYi Qu, Jixian Wan, Ruihan Li, Xinyuan Li, Han Li, Yang Li, Shengnan Huang, Tingting Zhang\u003csup\u003e\u0026nbsp;\u003c/sup\u003eperformed all data analyses and wrote the original manuscript. Yi Qu wrote and critically reviewed the manuscript. Dawei Yang and Dongliang Chen conceived, designed, and directed the study. All authors reviewed the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eHuman and Animal Rights\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis article does not involve any studies with human participants or animals conducted by any of the authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eFor this type of study, informed consent is not required.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eQiu JD, Xue XY, Hu C, Xu H, Kou DQ, Li R, Li M (2016) Comparison of Clinicopathological Features and Prognosis in Triple-Negative and Non-Triple Negative Breast Cancer. J Cancer 7:167\u0026ndash;173. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.7150/jca.10944\u003c/span\u003e\u003cspan address=\"10.7150/jca.10944\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFoulkes WD, Smith IE, Reis-Filho JS (2010) Triple-negative breast cancer. N Engl J Med. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMra1001389\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra1001389\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. 363:1938-48\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZou Y, Xie J, Zheng S, Liu W, Tang Y, Tian W, Deng X, Wu L, Zhang Y, Wong CW, Tan D, Liu Q, Xie X (2022) Leveraging diverse cell-death patterns to predict the prognosis and drug sensitivity of triple-negative breast cancer patients after surgery. Int J Surg (London England) 107:106936. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ijsu.2022.106936\u003c/span\u003e\u003cspan address=\"10.1016/j.ijsu.2022.106936\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeon-Ferre RA, Goetz MP (2023) Advances in systemic therapies for triple negative breast cancer. BMJ (Clinical Res ed 381:e071674. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1136/bmj-2022-071674\u003c/span\u003e\u003cspan address=\"10.1136/bmj-2022-071674\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang Y, Ge H, Zheng M, Cui Y, Fu Z, Wu X, Xia Y, Chen L, Wang Z, Wang S, Xie H (2019) Serum tRNA-derived fragments (tRFs) as potential candidates for diagnosis of nontriple negative breast cancer. J Cell Physiol 235:2809\u0026ndash;2824. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/jcp.29185\u003c/span\u003e\u003cspan address=\"10.1002/jcp.29185\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eManoochehri M, Borhani N, Gerh\u0026auml;user C, Assenov Y, Sch\u0026ouml;nung M, Hielscher T, Christensen BC, Lee MK, Gr\u0026ouml;ne HJ, Lipka DB, Br\u0026uuml;ning T, Brauch H, Ko YD, Hamann U (2023) DNA methylation biomarkers for noninvasive detection of triple-negative breast cancer using liquid biopsy. Int J Cancer 152:1025\u0026ndash;1035. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/ijc.34337\u003c/span\u003e\u003cspan address=\"10.1002/ijc.34337\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang L, Rong Y, Tang X, Yi K, Qi P, Hou J, Liu W, He Y, Gao X, Yuan C, Wang F (2022) Engineered exosomes as an in situ DC-primed vaccine to boost antitumor immunity in breast cancer. Mol Cancer 21:45. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s12943-022-01515-x\u003c/span\u003e\u003cspan address=\"10.1186/s12943-022-01515-x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu D, Wang YL, Wang KT, Wang Y, Dong XR, Tang J, Cui YL (2021) A Scientometrics Analysis and Visualization of Depressive Disorder. Curr Neuropharmacol 19:766\u0026ndash;786. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.2174/1570159x18666200905151333\u003c/span\u003e\u003cspan address=\"10.2174/1570159x18666200905151333\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAhmad P, Slots J (2021) A bibliometric analysis of periodontology. Periodontology 2000 85:237\u0026ndash;240. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/prd.12376\u003c/span\u003e\u003cspan address=\"10.1111/prd.12376\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFeng YX, Spezia M, Huang SF, Yuan CF, Zeng ZY, Zhang LH, Ji XJ, Liu W, Huang B, Luo WP, Liu B, Lei Y, Du S, Vuppalapati A, Luu HH, Haydon RC, He TC, Ren GS (2018) Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis. Genes Dis 5:77\u0026ndash;106. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.gendis.2018.05.001\u003c/span\u003e\u003cspan address=\"10.1016/j.gendis.2018.05.001\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA: A Cancer. J Clin 67:7\u0026ndash;30. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3322/caac.21387\u003c/span\u003e\u003cspan address=\"10.3322/caac.21387\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKalluri R, LeBleu VS (2020) The biology, function, and biomedical applications of exosomes. Sci 367. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1126/science.aau6977\u003c/span\u003e\u003cspan address=\"10.1126/science.aau6977\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKolovskaya OS, Zyuzyukina AV, Dassie JP, Zamay GS, Zamay TN, Boyakova NV, Khorzhevskii VA, Kirichenko DA, Lapin IN, Shchugoreva IA, Artyushenko PV, Tomilin FN, Veprintsev DV, Glazyrin YE, Minic Z, Bozhenko VK, Kudinova EA, Kiseleva YY, Krat AV, Slepov EV, Bukatin AS, Zukov RA, Shesternya PA, Berezovski MV, Giangrande PH, Kichkailo AS (2023) Monitoring of breast cancer progression via aptamer-based detection of circulating tumor cells in clinical blood samples. Front Mol Biosci 10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fmolb.2023.1184285\u003c/span\u003e\u003cspan address=\"10.3389/fmolb.2023.1184285\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbreu M, Cabezas-Sainz P, Pereira-Veiga T, Falo C, Abalo A, Morilla I, Curiel T, Cueva J, Rodr\u0026iacute;guez C, Varela-Pose V, Lago-Lest\u0026oacute;n R, Mondelo P, Palacios P, Moreno-Bueno G, Cano A, Garc\u0026iacute;a-Caballero T, Pujana M\u0026Aacute;, S\u0026aacute;nchez-Pi\u0026ntilde;\u0026oacute;n L, Costa C, L\u0026oacute;pez R, Muinelo-Romay L (2020) Looking for a Better Characterization of Triple-Negative Breast Cancer by Means of Circulating Tumor Cells. Journal of Clinical Medicine 9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/jcm9020353\u003c/span\u003e\u003cspan address=\"10.3390/jcm9020353\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBidard FC, Peeters DJ, Fehm T, Nol\u0026eacute; F, Gisbert-Criado R, Mavroudis D, Grisanti S, Generali D, Garcia-Saenz JA, Stebbing J, Caldas C, Gazzaniga P, Manso L, Zamarchi R, de Lascoiti AF, De Mattos-Arruda L, Ignatiadis M, Lebofsky R, van Laere SJ, Meier-Stiegen F, Sandri MT, Vidal-Martinez J, Politaki E, Consoli F, Bottini A, Diaz-Rubio E, Krell J, Dawson SJ, Raimondi C, Rutten A, Janni W, Munzone E, Cara\u0026ntilde;ana V, Agelaki SA, Almici C, Dirix L, Solomayer EF, Zorzino L, Johannes H, Reis JS, Pantel K, Pierga JY, Michiels S (2014) Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data. Lancet Oncol 15:406\u0026ndash;414. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/s1470-2045(14)70069-5\u003c/span\u003e\u003cspan address=\"10.1016/s1470-2045(14)70069-5\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFabisiewicz A, Szostakowska-Rodzos M, Zaczek AJ, Grzybowska EA (2020) Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value. Int J Mol Sci 21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijms21051671\u003c/span\u003e\u003cspan address=\"10.3390/ijms21051671\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen ZH, Zeng ZH, Wan QY, Liu XH, Qi JJ, Zu YL (2022) Targeted immunotherapy of triple-negative breast cancer by aptamer-engineered NK cells. Biomaterials 280:12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.biomaterials.2021.121259\u003c/span\u003e\u003cspan address=\"10.1016/j.biomaterials.2021.121259\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBryan S, Witzel I, Borgmann K, Oliveira-Ferrer L (2021) Molecular Mechanisms Associated with Brain Metastases in HER2-Positive and Triple Negative Breast Cancers. Cancers 13 \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/cancers13164137\u003c/span\u003e\u003cspan address=\"10.3390/cancers13164137\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaftaf R, Liu X, Singh S, Jia YZ, Dashzeveg NK, Hoffmann AD, El-Shennawy L, Ramos EK, Adorno-Cruz V, Schuster EJ, Scholten D, Patel D, Zhang YB, Davis AA, Reduzzi C, Cao Y, D'Amico P, Shen Y, Cristofanilli M, Muller WA, Varadan V, Liu HP (2021) ICAM1 initiates CTC cluster formation and trans-endothelial migration in lung metastasis of breast cancer. Nat Commun 12:15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41467-021-25189-z\u003c/span\u003e\u003cspan address=\"10.1038/s41467-021-25189-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eStravokefalou V, Stellas D, Karaliota S, Nagy BA, Valentin A, Bergamaschi C, Dimas K, Pavlakis GN (2023) Heterodimeric IL-15 (hetIL-15) reduces circulating tumor cells and metastasis formation improving chemotherapy and surgery in 4T1 mouse model of TNBC. Front Immunol 13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3389/fimmu.2022.1014802\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2022.1014802\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMa JL, Chen C, Fan ZM, Zhang Y, Ji JH, Wei DX, Zhang F, Sun B, Huang P, Ren LQ (2023) CircEGFR reduces the sensitivity of pirarubicin and regulates the malignant progression of triple-negative breast cancer via the miR-1299/EGFR axis. Int J Biol Macromol 244:16. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ijbiomac.2023.125295\u003c/span\u003e\u003cspan address=\"10.1016/j.ijbiomac.2023.125295\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLan FM, Zhang XD, Li HB, Yue X, Sun QH (2021) Serum exosomal lncRNA XIST is a potential non-invasive biomarker to diagnose recurrence of triple-negative breast cancer. J Cell Mol Med 25:7602\u0026ndash;7607. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/jcmm.16009\u003c/span\u003e\u003cspan address=\"10.1111/jcmm.16009\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDi Modica M, Regondi V, Sandri M, Iorio MV, Zanetti A, Tagliabue E, Casalini P, Triulzi T (2017) Breast cancer-secreted miR-939 downregulates VE-cadherin and destroys the barrier function of endothelial monolayers. Cancer Lett 384:94\u0026ndash;100. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.canlet.2016.09.013\u003c/span\u003e\u003cspan address=\"10.1016/j.canlet.2016.09.013\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang SJ, Wang DD, Zhong SL, Chen WQ, Wang FL, Zhang J, Xu WX, Xu D, Zhang Q, Li J, Zhang HD, Hou JC, Mao L, Tang JH (2021) Tumor-derived exosomal circPSMA1 facilitates the tumorigenesis, metastasis, and migration in triple-negative breast cancer (TNBC) through miR-637/Akt1/β-catenin (cyclin D1) axis. Cell Death Dis 12:20. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41419-021-03680-1\u003c/span\u003e\u003cspan address=\"10.1038/s41419-021-03680-1\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFigueira I, Godinho-Pereira J, Galego S, Maia J, Hask\u0026oacute; J, Moln\u0026aacute;r K, Malh\u0026oacute; R, Costa-Silva B, Wilhelm I, Krizbai IA, Brito MA (2021) MicroRNAs and Extracellular Vesicles as Distinctive Biomarkers of Precocious and Advanced Stages of Breast Cancer Brain Metastases Development. Int J Mol Sci 22:21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/ijms22105214\u003c/span\u003e\u003cspan address=\"10.3390/ijms22105214\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChaudhary P, Gibbs LD, Maji S, Lewis CM, Suzuki S, Vishwanatha JK (2020) Serum exosomal-annexin A2 is associated with African-American triple-negative breast cancer and promotes angiogenesis. Breast Cancer Res 22. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1186/s13058-020-1251-8\u003c/span\u003e\u003cspan address=\"10.1186/s13058-020-1251-8\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaji S, Chaudhary P, Akopova I, Nguyen PM, Hare RJ, Gryczynski I, Vishwanatha JK (2017) Exosomal Annexin II Promotes Angiogenesis and Breast Cancer Metastasis. Mol Cancer Res 15:93\u0026ndash;105. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1158/1541-7786.Mcr-16-0163\u003c/span\u003e\u003cspan address=\"10.1158/1541-7786.Mcr-16-0163\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJung HH, Kim JY, Lim JE, Im YH (2020) Cytokine profiling in serum-derived exosomes isolated by different methods. Sci Rep 10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41598-020-70584-z\u003c/span\u003e\u003cspan address=\"10.1038/s41598-020-70584-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUslu D, Abas BI, Demirbolat GM, Cevik O (2022) Effect of platelet exosomes loaded with doxorubicin as a targeted therapy on triple-negative breast cancer cells. Mol Divers. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s11030-022-10591-6\u003c/span\u003e\u003cspan address=\"10.1007/s11030-022-10591-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao LW, Gu CY, Gan Y, Shao LL, Chen HW, Zhu HY (2020) Exosome-mediated siRNA delivery to suppress postoperative breast cancer metastasis. J Control Release 318:1\u0026ndash;15. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.jconrel.2019.12.005\u003c/span\u003e\u003cspan address=\"10.1016/j.jconrel.2019.12.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHolstege H, Joosse SA, van Oostrom CTM, Nederlof PM, de Vries A, Jonkers J (2009) High Incidence of Protein-Truncating\u0026thinsp;\u0026lt;\u0026thinsp;i\u0026thinsp;\u0026gt;\u0026thinsp;TP53\u0026thinsp;Mutations in BRCA1-Related Breast Cancer. Cancer Res 69:3625\u0026ndash;3633. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1158/0008-5472.Can-08-3426\u003c/span\u003e\u003cspan address=\"10.1158/0008-5472.Can-08-3426\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSchwarzenbach H, Hoon DSB, Pantel K (2011) Cell-free nucleic acids as biomarkers in cancer patients. Nat Rev Cancer 11:426\u0026ndash;437. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/nrc3066\u003c/span\u003e\u003cspan address=\"10.1038/nrc3066\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRiva F, Bidard FC, Houy A, Saliou A, Madic J, Rampanou A, Hego C, Milder M, Cottu P, Sablin MP, Vincent-Salomon A, Lantz O, Stern MH, Proudhon C, Pierga JY (2017) Patient -Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple -Negative Breast Cancer. Clin Chem 63:691\u0026ndash;699. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1373/clinchem.2016.262337\u003c/span\u003e\u003cspan address=\"10.1373/clinchem.2016.262337\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eForshew T, Murtaza M, Parkinson C, Gale D, Tsui DWY, Kaper F, Dawson SJ, Piskorz AM, Jimenez-Linan M, Bentley D, Hadfield J, May AP, Caldas C, Brenton JD, Rosenfeld N (2012) Noninvasive Identification and Monitoring of Cancer Mutations by Targeted Deep Sequencing of Plasma DNA. Sci Transl Med 4:12. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1126/scitranslmed.3003726\u003c/span\u003e\u003cspan address=\"10.1126/scitranslmed.3003726\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMadic J, Kiialainen A, Bidard FC, Birzele F, Ramey G, Leroy Q, Frio TR, Vaucher I, Raynal V, Bernard V, Lermine A, Clausen I, Giroud N, Schmucki R, Milder M, Horn C, Spleiss O, Lantz O, Stern MH, Pierga JY, Weisser M, Lebofsky R (2015) Circulating tumor DNA and circulating tumor cells in metastatic triple negative breast cancer patients. Int J Cancer 136:2158\u0026ndash;2165. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/ijc.29265\u003c/span\u003e\u003cspan address=\"10.1002/ijc.29265\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen YH, Hancock BA, Solzak JP, Brinza D, Scafe C, Miller KD, Radovich M (2017) Next-generation sequencing of circulating tumor DNA to predict recurrence in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy. npj Breast Cancer 3:6. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41523-017-0028-4\u003c/span\u003e\u003cspan address=\"10.1038/s41523-017-0028-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePellerino A, Brastianos PK, Rud\u0026agrave; R, Soffietti R (2021) Leptomeningeal Metastases from Solid Tumors: Recent Advances in Diagnosis and Molecular Approaches. Cancers 13:34. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/cancers13122888\u003c/span\u003e\u003cspan address=\"10.3390/cancers13122888\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOrtolan E, Appierto, Silvestri M, Miceli R, Veneroni S, Folli S, Pruneri G, Vingiani A, Belfiore A, Cappelletti, Vismara M, Dell'Angelo F, De Cecco L, Bianchi G, de Braud FG, Daidone MG, Di Cosimo S (2021) Blood-based genomics of triple-negative breast cancer progression in patients treated with neoadjuvant chemotherapy. ESMO Open 6:10. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.esmoop.2021.100086\u003c/span\u003e\u003cspan address=\"10.1016/j.esmoop.2021.100086\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCavallone L, Aguilar-Mahecha A, Lafleur J, Brousse S, Aldamry M, Roseshter T, Lan C, Alirezaie N, Bareke E, Majewski J, Ferrario C, Hassan S, Discepola F, Seguin C, Mihalcioiu C, Marcus EA, Robidoux A, Roy JA, Pelmus M, Basik M (2020) Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer. Sci Rep 10:13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1038/s41598-020-71236-y\u003c/span\u003e\u003cspan address=\"10.1038/s41598-020-71236-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKim H, Kim YJ, Park D, Park WY, Choi DH, Park W, Cho WK, Kim N (2021) Dynamics of circulating tumor DNA during postoperative radiotherapy in patients with residual triple-negative breast cancer following neoadjuvant chemotherapy: a prospective observational study. Breast Cancer Res Treat 189:167\u0026ndash;175. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s10549-021-06296-3\u003c/span\u003e\u003cspan address=\"10.1007/s10549-021-06296-3\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFoulkes WD, Smith IE, Reis JS (2010) Triple-Negative Breast Cancer. N. Engl. J Med 363:1938\u0026ndash;1948. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1056/NEJMra1001389\u003c/span\u003e\u003cspan address=\"10.1056/NEJMra1001389\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePascual J, Lim JSJ, Macpherson IR, Armstrong AC, Ring A, Okines AFC, Cutts RJ, Herrera-Abreu MT, Garcia-Murillas I, Pearson A, Hrebien S, Gevensleben H, Proszek PZ, Hubank M, Hills M, King J, Parmar M, Prout T, Finneran L, Malia J, Swales KE, Ruddle R, Raynaud FI, Turner A, Hall E, Yap TA, Lopez JS, Turner NC (2021) Triplet Therapy with Palbociclib, Taselisib, and fulvestrant in \u0026lt;\u0026thinsp;i\u0026thinsp;\u0026gt;\u0026thinsp;PIK3CA-Mutant Breast Cancer and Doublet Palbociclib and Taselisib in Pathway-Mutant Solid Cancers. Cancer Discov 11:92\u0026ndash;107. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1158/2159-8290.Cd-20-0553\u003c/span\u003e\u003cspan address=\"10.1158/2159-8290.Cd-20-0553\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSukumar J, Gast K, Quiroga D, Lustberg M, Williams N (2021) Triple-negative breast cancer: promising prognostic biomarkers currently in development. Expert Rev Anticancer Ther 21:135\u0026ndash;148. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/14737140.2021.1840984\u003c/span\u003e\u003cspan address=\"10.1080/14737140.2021.1840984\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Triple-negative breast cancer (TNBC), Liquid biopsy, Bibliometrics, Exosomes, Circulating tumor cells (CTCs), Circulating tumor DNA (ctDNA)","lastPublishedDoi":"10.21203/rs.3.rs-4203189/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4203189/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLiquid biopsy has emerged as a significant technique in the field of triple-negative breast cancer, garnering widespread attention since 2012. Despite this, there remains a notable absence of bibliometric assessment in this area. This study screened 506 pieces of literature obtained from Web of Science (WoS) searches and selected 347 papers published between 2012 and 2024. Various software tools, including \u003cem\u003eVOSviewer\u003c/em\u003e, \u003cem\u003eCiteSpace\u003c/em\u003e, \u003cem\u003eBibliomatrix\u003c/em\u003e, and \u003cem\u003eScimago Graphica\u003c/em\u003e were used to visualize the results of the analyses. Through careful examination of visual graphs, this study conducted in-depth profiling mining, suggesting great potential and promise in this area. The linkage map of countries highlights the central roles played by the USA and China in this field over the past twelve years. Furthermore, the analysis of literature co-citations reveals a predominant focus on subtypes, cell models, and targeted therapies. Keyword analysis indicates previous emphasis on sensitive targets and advancements in the nano-field. Moreover, the evolution of keywords over time illustrates a transition from mechanistic inquiries to investigations spanning diagnosis, immunotherapy, and prognosis. These results offer valuable insights into the research process and potential future directions. Additionally, this paper integrates keywords, co-cited cores, coupling centrality, and visual analysis results of the most cited literature, using techniques such as timeline graph clustering and emergent words. Major hotspots are summarised, such as \"biomarker\", \"target\", \"biological model\", and \"Immunotherapy inhibitors\".\u003c/p\u003e","manuscriptTitle":"Research History, Current Trends, and Future Prospects of Liquid Biopsy in Triple-Negative Breast Cancer: An Analysis from a Global Perspective","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-05 12:57:07","doi":"10.21203/rs.3.rs-4203189/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e82b0e26-abc5-4802-bf6f-f0676db71a88","owner":[],"postedDate":"April 5th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-04-10T13:06:33+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-05 12:57:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4203189","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4203189","identity":"rs-4203189","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}