Breast Cancer : Targets and Therapy最新文献

{"title":"Bilateral Primary Breast Cancer: Current Evidence and Future Perspectives.","authors":"Huixi Zhong, Di Lu, Yaling Zeng, Xihui Tu, Purong Zhang, Tengfei Xing","doi":"10.2147/BCTT.S615577","DOIUrl":"10.2147/BCTT.S615577","url":null,"abstract":"<p><p>Bilateral primary breast cancer (BPBC) accounts for 2-12% of all breast cancers, with an increasing incidence trend. However, its clinical management remains challenged by the absence of unified diagnostic criteria, lack of evidence-based therapeutic guidelines, incomplete prognostic assessment frameworks, and a paucity of data from Asian populations. This narrative review critically synthesizes literature from PubMed, Web of Science, and CNKI databases (2020-2025) across seven dimensions: diagnosis and differential diagnosis, clinicopathological features, risk factors, imaging, genetics, treatment, and prognosis. Current evidence demonstrates that SBBC and MBBC exhibit significant heterogeneity in age at onset, molecular subtype distribution, and prognosis, with bilateral receptor discordance rates of 11-23%, mandating separate evaluation of each side; all current treatment recommendations are extrapolated from unilateral breast cancer evidence, leaving decisions in cases of subtype discordance without evidence-based support; and existing genetic risk models and clinical evidence are predominantly derived from Western populations, with only limited single-center retrospective data available from Asian populations but systematic, high-quality evidence remaining insufficient, such that direct application carries a risk of systematic bias. This review aims to provide an evidence-based reference for standardized clinical practice, emphasizing the urgent need to establish unified diagnostic criteria, develop population-specific risk models for Asian populations, and conduct dedicated prospective trials.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"615577"},"PeriodicalIF":3.6,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13532941/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>MST1</i> and <i>CPNE1</i> Emerge as Candidate Targets in Breast Cancer: Integration of Mendelian Randomization, Multi-omics Validation, and Functional Interrogation.","authors":"Meng Jiang, Qilong Wang, Hong Xu","doi":"10.2147/BCTT.S611734","DOIUrl":"10.2147/BCTT.S611734","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer remains a leading cause of female mortality worldwide, with therapeutic benefit limited by tumor heterogeneity and drug resistance. Identification of novel therapeutic targets through integration of genetic causality inference and functional validation is urgently needed.</p><p><strong>Methods: </strong>Plasma protein quantitative trait loci (pQTL) from the Fenland cohort (~10,700 individuals) and the FinnGen R10 SomaScan subset (n = 828) were integrated with breast cancer genome-wide association study data from the Breast Cancer Association Consortium (122,977 cases and 105,974 controls). Causal protein-disease relationships were inferred using summary-data-based Mendelian randomization (SMR), with colocalization and HEIDI tests. Multi-level validation was performed using TCGA-BRCA transcriptomic data. Functional validation included CCK-8, EdU, wound healing, Transwell invasion, and flow cytometry apoptosis analysis evaluated <i>CPNE1</i> knocdown and/or overexpression of <i>the MST1 gene</i> which encodes macrophage-simulating protein (MSP).</p><p><strong>Results: </strong>SMR identified 23 proteins in Fenland and 10 in FinnGen at FDR < 0.05. MST1/MSP and CPNE1 were supported in both datasets with PP.H4 ≥ 0.80 and non-significant HEIDI tests. Genetically predicted circulating MSP was positively associated with breast cancer risk, whereas circulating CPNE1 showed an inverse association. TCGA-BRCA showed higher <i>CPNE1</i> mRNA in tumors (P = 2.57×10⁻²⁵) and lower <i>MST1</i> mRNA (P = 3.04×10⁻²³). <i>CPNE1</i> expression was highest in triple-negative breast cancer and correlated positively with clinical stage (ρ = 0.211), whereas <i>MST1</i> expression was lowest in triple-negative breast cancer and correlated inversely with stage (ρ = -0.164). In T47D and MDA-MB-231 cells, <i>CPNE1</i> knockdown and <i>MST1</i> overexpression each reduced proliferation, migration, and invasion and increased apoptosis; the combined group showed greater changes than either single intervention.</p><p><strong>Conclusion: </strong>This study prioritizes <i>the MST1 gene</i>, which encodes MSP, and <i>CPNE1</i> as candidate proteins for further investigation in breast cancer. However, the circulating-protein associations, tumor-mRNA patterns, and cell-autonomous perturbations represent distinct and directionally discordant biological contexts. The findings therefore support context-dependent candidate roles and justify mechanistic, in vivo, and formal interaction studies, but do not yet establish therapeutic efficacy or synergy.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"611734"},"PeriodicalIF":3.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863610","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Pretreatment ANR and IronMLR With Pathological Response Following Neoadjuvant Chemotherapy in Breast Cancer.","authors":"Emre Özge, Rıza Umar Gürsu, Bünyamin Güney, Özgür Han, Çiğdem Yıldırım, İlkay Gültürk, Servet Emir, Hülya Nur Özge","doi":"10.2147/BCTT.S623894","DOIUrl":"10.2147/BCTT.S623894","url":null,"abstract":"<p><strong>Background: </strong>Reliable biomarkers for predicting response to neoadjuvant chemotherapy (NAC) in breast cancer remain limited. This study evaluated the association of pretreatment Albumin-to-Neutrophil Ratio (ANR) and IronMLR with pathological response following NAC.</p><p><strong>Methods: </strong>This retrospective study included 71 patients with breast cancer treated with NAC. Pretreatment inflammatory indices were calculated from routine blood samples obtained before treatment initiation. ANR and IronMLR were compared across pathological response groups. Receiver operating characteristic (ROC) analysis was performed to evaluate predictive performance.</p><p><strong>Results: </strong>The mean age was 53.9±10.6 years, and pathological complete response (pCR) was achieved in 30 patients (42.3%). ANR was not significantly associated with pathological response (p=0.121). In contrast, IronMLR levels differed significantly among complete responders, partial responders, and non-responders (p<0.001). ROC analysis demonstrated favorable discriminatory performance of IronMLR for predicting treatment response, with an area under the curve of 0.909 (95% CI, 0.832-0.986; p<0.001). An IronMLR cut-off value of 175.40 yielded 77.4% sensitivity and 77.8% specificity. Patients with IronMLR ≥175.40 exhibited significantly higher response rates than those with lower values (96.0% vs 66.7%, p=0.001).</p><p><strong>Conclusion: </strong>Pretreatment IronMLR was significantly associated with pathological response following NAC in patients with breast cancer, whereas ANR showed no significant association. Given its simplicity and accessibility, IronMLR may represent a potentially useful biomarker for treatment stratification. Further prospective multicenter studies are warranted to validate these findings.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"623894"},"PeriodicalIF":3.6,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MCV-Neutropenia Risk Score and Overall Survival in HR+/HER2- Advanced Breast Cancer: A Multicenter Retrospective Landmark Analysis.","authors":"Fatih Atalah, Aydın Acarbay, Akgün Karakök, İsmail Nazlı, Onur Alkan, Okan Aydın, Oğuzhan Selvi, Mehmet Beşiroğlu, Mahmut Gümüş","doi":"10.2147/BCTT.S624272","DOIUrl":"10.2147/BCTT.S624272","url":null,"abstract":"<p><strong>Background: </strong>Predicting long-term benefit from CDK4/6 inhibitors in HR+/HER2- advanced breast cancer remains challenging in routine clinical practice. We evaluated whether a simple composite index integrating early neutropenia and mean corpuscular volume change, termed the MCV-Neutropenia Risk Score (MNRS), could improve early prognostic stratification.</p><p><strong>Methods: </strong>In this multicenter retrospective study, 432 patients were screened, and 273 patients who were alive and evaluable at the predefined 3-month landmark were included in the final analysis. Grade 2-3 neutropenia during the first three months and ΔMCV ≥10 fL at the landmark assessment were assigned one point each to construct the MNRS (range, 0-2). Landmark overall survival (OS), measured from the 3-month landmark, was evaluated using Kaplan-Meier estimates and Cox proportional hazards regression. Internal bootstrap validation with 1,000 resamples was performed.</p><p><strong>Results: </strong>After a median landmark follow-up of 44.9 months, 77 deaths were recorded. Grade 2-3 neutropenia occurred in 205 patients (75.1%), ΔMCV ≥10 fL in 93 patients (34.1%), and 66 patients (24.2%) had an MNRS of 2. Higher MNRS categories were associated with progressively more favorable landmark OS (log-rank p = 0.009). In the final center-stratified multivariable model, each one-point increase in MNRS was independently associated with a lower risk of death (HR 0.555, 95% CI 0.381-0.808; p = 0.002). Internal bootstrap validation supported the stability of MNRS in the multivariable model.</p><p><strong>Conclusion: </strong>Among patients who were alive and evaluable at the 3-month landmark, higher MNRS was independently associated with more favorable subsequent landmark OS. MNRS may represent an exploratory and complementary approach to early risk stratification using routinely available hematologic parameters. Because both neutropenia and MCV changes may be influenced by treatment exposure and other clinical factors, prospective external validation is required before clinical application.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"624272"},"PeriodicalIF":3.6,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13499554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148788175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and Validation of a Machine-Learning Deep Plasma Proteome Classifier for Early-Stage Breast Cancer Detection.","authors":"Alec Horrmann, Yash Travadi, Jacob Carey, Ella Boytim, Kevin Mallery, Grant Schaap, Carissa Rungkittikhun, Kaylee Judith Kamalanathan, Nathaniel R Bristow, Catalina Galeano-Garces, Adam Groth, Harrison Ball, Alexa R Hesch, Pooja Advani, Justin Hwang, Badrinath R Konety, Justin M Drake","doi":"10.2147/BCTT.S609238","DOIUrl":"10.2147/BCTT.S609238","url":null,"abstract":"<p><strong>Introduction: </strong>Proteome-guided liquid biopsy tests hold immense promise for the future of early cancer detection. Here, we analyzed the plasma proteome of 1,259 biobanked samples consisting of healthy women and women with breast cancer. The Astrin Biosciences' breast cancer early detection test is a laboratory developed test (LDT) that uses a protein-based machine learning classifier to identify breast cancer with high accuracy.</p><p><strong>Methods: </strong>The classifier was trained on 845 women (466 healthy and 379 with newly diagnosed, treatment naïve breast cancer) and validated on 397 women (195 healthy and 202 breast cancer) from the same collection cohort (held-out validation). All plasma samples were processed in an automated, blinded manner coupled with semi-quantitative, label-free mass spectrometry (MS)-based analysis.</p><p><strong>Results: </strong>The held-out validation performance achieved 92.3% specificity (180/195; 95% Wilson CI: 87.7-95.3%), 92.6% sensitivity (187/202; 95% Wilson CI: 88.1-95.4%) and an AUC of 0.975 (95% Bootstrap CI: 0.961-0.987). Observed sensitivity remained high across all breast cancer stages and pathological and molecular subtypes, albeit with small sample sizes for some subtypes. Gene set enrichment analyses (GSEA) identified epithelial-to-mesenchymal transition (EMT) and PI3K-AKT signaling as enriched in the breast cancer samples, highlighting that our test may possibly identify cancer-related proteins in early-stage patients. A simulated population demonstrates the utility of our test as a supplement to mammography, detecting nearly all (93%) breast cancers missed by mammography and reducing the number of false positives relative to MRI and Contrast-Enhanced Mammography (CEM) alone by >10-fold.</p><p><strong>Discussion: </strong>Overall, our proteomic data demonstrates high sensitivity and specificity in women with breast cancer, especially at early stages, and is a favorable supplemental test post mammogram.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"609238"},"PeriodicalIF":3.6,"publicationDate":"2026-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13431460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomal miR-21 Derived from Paclitaxel-Resistant Breast Cancer Cells Promotes Chemoresistance in Breast Cancer via p53/PI3K/AKT/mTOR Signaling.","authors":"Yanyan Wang, Qing Cai","doi":"10.2147/BCTT.S615413","DOIUrl":"10.2147/BCTT.S615413","url":null,"abstract":"<p><strong>Objective: </strong>To investigate whether exosomes derived from paclitaxel (PTX)-resistant breast cancer cells confer chemoresistance to parental cells and to explore the involvement of the p53/PI3K/AKT/mTOR signaling pathway in this process.</p><p><strong>Methods: </strong>Exosomes were isolated from PTX-sensitive and PTX-resistant breast cancer cells (MCF-7 and MDA-MB-231) and characterized by transmission electron microscopy, nanoparticle tracking analysis, and detection of exosomal markers. Bioinformatics analyses were performed to predict microRNAs potentially targeting TP53. Functional assays, including Cell Counting Kit-8 (CCK-8), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), quantitative real-time PCR (qRT-PCR), and Western blotting, were used to assess drug sensitivity, apoptosis, and pathway-related molecular changes in recipient cells. MicroRNA inhibition and p53 overexpression approaches were applied for mechanistic validation, and key experiments were conducted in multiple breast cancer cell models.</p><p><strong>Results: </strong>Exosomes derived from PTX-resistant cells significantly enhanced PTX resistance and attenuated apoptosis-related changes in recipient cells. Inhibition of exosomal miR-21 or restoration of p53 expression reversed these effects. Similar results were observed across different breast cancer subtypes.</p><p><strong>Conclusion: </strong>These findings indicate that exosomal miR-21 derived from PTX-resistant breast cancer cells may contribute to chemoresistance, at least in part, by suppressing p53 and modulating PI3K/AKT/mTOR pathway activation.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"615413"},"PeriodicalIF":3.6,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13426359/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrative Network-Based Transcriptomic Analysis Identifies Niclosamide as a Candidate Repositioned Drug for Breast Cancer.","authors":"Busra Aydin, Beyza Nur Okutan, Fatmanur Elif Sara, Gulcihan Gulseren, Raghu Sinha","doi":"10.2147/BCTT.S606551","DOIUrl":"10.2147/BCTT.S606551","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer (BC) is a highly heterogeneous malignancy, and current treatments often suffer from toxicity, limited selectivity, and high cost. This study aimed to integrate transcriptome-level data, multi-layered network analysis, and drug repositioning strategies to identify candidate diagnostic and prognostic biomarkers for BC and propose potential repositioned drug candidates.</p><p><strong>Methods: </strong>Differentially expressed genes (DEGs) were identified from the GSE42568 dataset (|log₂FC| > 1 and p < 0.05). Functional enrichment analyses were conducted using GO and KEGG. Three biological interaction layers - protein-protein interactions, transcription factors, and miRNA-mRNA interactions were constructed, and hub nodes were identified using topological metrics. Kaplan-Meier analyses assessed survival associations. PCA evaluated sample separation across datasets in GSE42568, GSE113865, and GSE22820. Drug repositioning was performed using L1000CDS², and in vitro validation of a top drug candidate (niclosamide) and an exploratory comparative compound (amitriptyline) was performed using MCF-7 cells, including viability and combination assays.</p><p><strong>Results: </strong>A total of 4266 DEGs were identified. Network analyses revealed 37 hub signatures, 11 of which-<i>ESR1, RECQL4, FOS, BCL2, CXCL8, TRIM25, EGR1, CDH1, KRAS, PTGS2</i>, and <i>IL6</i> were associated with survival outcomes. PCA demonstrated clear separation between healthy and BC samples. Drug repositioning identified eight candidates, with niclosamide as the top hit. In vitro assays showed marked reduction in cell viability at 5 µM niclosamide and 25 µM amitriptyline after 24 h treatment. No significant additive effect was observed in the combination treatment.</p><p><strong>Conclusion: </strong>This integrative approach revealed candidate BC-specific biomarkers and identified niclosamide as a potential repositioned therapeutic. These findings remain exploratory and do not provide definitive clinical evidence. Further validation across additional models and clinical settings is required.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"606551"},"PeriodicalIF":3.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411154/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long Non-Coding RNA PVT1 Promotes Doxorubicin Resistance by Inhibiting Ferroptosis in Breast Cancer.","authors":"Dan Zhao, Zheqiong Tan, Weiqun Chen, Shuiyi Liu, Tangwei Wu, Xiaoyi Li, Yuan Xiang, Hui Wang, Zhongxin Lu","doi":"10.2147/BCTT.S583235","DOIUrl":"10.2147/BCTT.S583235","url":null,"abstract":"<p><strong>Background: </strong>There is growing evidence that long non-coding RNAs (lncRNAs) play crucial roles in cancer progression and therapy. Our previous study showed that the lncRNA plasmacytoma variant translocation 1 (PVT1) regulates tumor growth and metastasis in breast cancer (BC). As a conventional chemotherapeutic drug, doxorubicin (DOX) resistance continues to be a major challenge in BC treatment. This study aimed to explore the role and underlying mechanism of PVT1 in doxorubicin-resistant BC.</p><p><strong>Methods: </strong>Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and Western blotting (WB) were carried out to detect gene and protein expression levels. The extent of ferroptosis was measured based on the cellular glutathione (GSH) levels and total or lipid reactive oxygen species (ROS) levels. An in-situ tumor implantation model in nude mice was employed to validate the mechanism in vivo. Transcriptome analysis was conducted to identify downstream target genes.</p><p><strong>Results: </strong>This study found that PVT1 was highly expressed in the plasma of drug-resistant patients and drug-resistant cell lines. Silencing PVT1 reduced cellular glutathione level, increased reactive oxygen species (ROS) and lipid peroxidation (LPO), while ferroptosis inhibition in rescue experiments partially reversed the oxidative stress. In-vivo study confirmed that silencing PVT1 increased the sensitivity of BC cells to doxorubicin treatment. Transcriptomic sequencing revealed that solute carrier family 3 member 2 (SLC3A2) was the most potential target gene of PVT1, which was confirmed in PVT1-silenced cell models.</p><p><strong>Conclusion: </strong>Mechanistically, PVT1 increased SLC3A2 expression, thus inhibiting ferroptosis and promoting doxorubicin resistance in BC, indicating that PVT1 could be a promising therapeutic target for doxorubicin-resistant BC patients.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"583235"},"PeriodicalIF":3.6,"publicationDate":"2026-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13411150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148618439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen-Driven Breast Carcinogenesis in a Rat Model is Linked to Retroelement Activation and Inflammation and is Susceptible to Lamivudine Treatment.","authors":"Valentina Evdokimova, Zhenbo Zhang, Peter Ruzanov, Minsheng Hung, Naghmeh Khoshgoo, Suky Zheng, Mary Anne Quintayo, Lincoln D Stein, Jane Bayani, Laszlo Radvanyi","doi":"10.2147/BCTT.S608709","DOIUrl":"10.2147/BCTT.S608709","url":null,"abstract":"<p><strong>Background: </strong>Despite significant progress in treating estrogen receptor (ER)-positive breast cancer (BC), the recurrence risk remains high and mechanisms driving initial ductal tumorigenesis is unclear. Given an emerging role of LINE-1 (L1), HERV-K and other endogenous retroviral elements (EREs) in cancer, we tested the hypothesis that their expression can be induced by estrogen and blocked by treatment with lamivudine (3TC), an HIV-1 drug that can also inhibit <i>L1</i> and <i>HERV-K</i> encoded reverse transcriptases (RTs) and ERE propagation.</p><p><strong>Methods: </strong>This is a preclinical study using the well-established ACI rat model of spontaneous estrogen-driven BC to examine the earliest stages of cancer development and the effects of 3TC. Rat mammary glands and peripheral blood mononuclear cells (PBMCs) were analyzed by immunohistochemistry (IHC) and RNA sequencing (RNAseq). A panel of human BC cell lines and tissue microarrays (TMAs) were assessed by RT-qPCR, immunoblotting and IHC to evaluate ERE RNA and protein expression and a potential association with the ER- and FOXA1- positive BC.</p><p><strong>Results: </strong>Development of estrogen-induced ER⁺ and FOXA1⁺ pre-invasive ductal tumors in rat mammary glands was accompanied by systemic inflammation and upregulation of ERE RNAs in mammary glands and PBMCs; these effects were attenuated by oral administration of 3TC. <i>L1</i> and <i>HERV</i> RNAs and proteins were also detected in human BC cell lines and in tumor tissues with high ER and FOXA1 protein levels, suggesting that their expression is an intrinsic part of the ER- and FOXA1- driven oncogenic programs.</p><p><strong>Conclusion: </strong>Using a rat model, our study demonstrates estrogen dependent ERE expression in pre-invasive ER⁺FOXA1⁺ mammary tumor cells and in circulating immune cells, activation of innate immune responses, and the inhibitory effects of 3TC. ERE RNAs and proteins are also highly expressed in human ER⁺FOXA1⁺ breast cancers, warranting further investigation into their functions and a potential use of 3TC as a preventive strategy for reducing a risk of cancer progression, especially in woman with ER⁺FOXA1⁺ tumors.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"608709"},"PeriodicalIF":3.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-1911-3p Regulates Malignant Biological Behaviors and Glycolytic Activity of Triple-Negative Breast Cancer via FBLN5.","authors":"Linna Kong, Huihui Zhang, Xufang Sui, Xueping Peng, Tiantian Sun","doi":"10.2147/BCTT.S615715","DOIUrl":"10.2147/BCTT.S615715","url":null,"abstract":"<p><strong>Background and objectives: </strong>Based on previous reports demonstrating the clinical potential of miR-1911-3p in breast cancer, its function and mechanisms in the development of TNBC were investigated, aiming to identify a novel biomarker.</p><p><strong>Materials and methods: </strong>Paired tissues were sampled from 128 TNBC patients, and miR-1911-3p levels were compared between tumor and normal tissues. The clinical significance of miR-1911-3p was evaluated from the perspective of disease severity and patients' prognosis. In vitro, the regulatory effects of miR-1911-3p on the malignant biological behaviors were assessed based on cell growth, motility, and glycolytic activity in MDA-MB-231 and HCC1806 cells. The mechanism evaluation was performed focusing on FBLN5 through luciferase reporter assay and related reversal experiments by co-regulating miR-1911-3p and FBLN5.</p><p><strong>Results: </strong>Significant upregulation of miR-1911-3p was observed in tumor tissues of TNBC patients (fold change of 1.35), which was associated with advanced TNM stage, higher Ki67 levels, and occurrence of lymph node metastasis. miR-1911-3p (HR = 3.036) was identified as an independent prognostic factor predicting 5-year recurrence-free survival (log‑rank <i>P</i> = 0.036) of TNBC patients. Consistent elevation of miR-1911-3p was also observed in TNBC cells, and its knockdown dramatically suppressed cell proliferation, migration, and invasion. Glycolytic activity was revealed to mediate the regulation of cell biological functions. FBLN5 was identified as a downstream target of miR-1911-3p, and negative regulation of its expression by miR-1911-3p was observed. Silencing FBLN5 could reverse the tumor‑suppressive effect of miR-1911-3p on TNBC cells, which was considered the major molecular mechanism.</p><p><strong>Conclusion: </strong>miR-1911-3p was identified as an independent prognostic biomarker for TNBC. Different from previously reporter miRNAs, miR-1911-3p regulated glycolytic activity-dependent cell growth and motility by targeting FBLN5, indicating its potential in serving as therapeutic target for TNBC.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"615715"},"PeriodicalIF":3.6,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13404179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}