Breast Cancer : Targets and Therapy最新文献

{"title":"ADPB Sensitivity in Breast Cancer is Correlated with LAT1 Expression: An in vitro Study of a Novel Theranostic Candidate.","authors":"Kharisma Perdani Kusumahstuti, Holis Abdul Holik, Muhammad Hasan Bashari, Arifudin Achmad, Shaharum Shamsuddin, Achmad Hussein Sundawa Kartamihardja","doi":"10.2147/BCTT.S564513","DOIUrl":"10.2147/BCTT.S564513","url":null,"abstract":"<p><strong>Introduction: </strong>The most common cancer in women worldwide is breast cancer. Current systemic chemotherapies do not target specific cells, which makes them toxic to normal cells. The L-type amino acid transporter 1 (LAT1) is overexpressed in a lot of cancers, also in breast cancer. Few ligand such as JPH203 (KYT-0353), a known tyrosine analogue that specifically blocks LAT1, but have limitation. It has led to efforts to create next-generation LAT1 inhibitors or prodrugs with better qualities for target therapy or diagnostic.</p><p><strong>Purpose: </strong>We investigated a new agent (S)-2-amino-4-(3,5-dichlorophenyl) butanoic acid (ADPB) as a new LAT1 inhibitor in three breast cancer cell lines: MCF-7 luminal A, HCC1954 HER2+, and MDA-MB-231 triple-negative. We hypothesized that the levels of LAT1 expression would influence the efficacy of ADPB. This could lead to a treatment that is more targeted and less harmful.</p><p><strong>Methods: </strong>We used RT-qPCR to determine the LAT1 mRNA expression in each cell line and MTT for find IC₅₀ values. These cells were given ADPB (0-160 µM) for 72 hours. There were three replication tests.</p><p><strong>Results: </strong>ADPB diminished the viability of cells in all cell lines, and the effect was dose-dependent. MDA-MB-231 was the most sensitive cell line (IC₅ ₀ = 118,1 µM 95% Cl (118,25<b>-</b>118,48), HCC-1954 was the middle-sensitive cell line (IC₅ ₀ = 126,2 µM 95% Cl (126,11<b>-</b>126,68), and MCF-7 was the least sensitive cell line (IC₅ ₀ = 127,3 µM 95% Cl (127,9<b>-</b>131,23). Study found an inverse relationship between LAT1 expression and IC₅ ₀ in all cell lines, with higher LAT1 levels correlated with lower IC₅ ₀.</p><p><strong>Conclusion: </strong>In this exploratory in vitro study, ADPB predominantly induces cytostatic effects, with cellular sensitivity associated with LAT1 expression in breast cancer cell line.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"564513"},"PeriodicalIF":3.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13159746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926261","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":"Immune Checkpoint Blockade and Emerging Combination Platforms in Breast Cancer: A Narrative Review.","authors":"Maryam Abbaspour, Nafiseh Esmaeil, Vajihe Akbari, Mohammad Ghoreishi, Haniyeh Rafiepoor","doi":"10.2147/BCTT.S588323","DOIUrl":"10.2147/BCTT.S588323","url":null,"abstract":"<p><p>This narrative review examines recent progress in immunotherapy for breast cancer (BC), focusing on immune checkpoint inhibitors (ICIs) alone and in combination with other modalities. Landmark trials such as KEYNOTE-522 and IMpassion130 have established the efficacy of pembrolizumab and atezolizumab in triple-negative breast cancer (TNBC). However, BC remains a leading cause of cancer-related fatalities, underscoring the need for novel approaches. We synthesize combination strategies into three mechanistic categories: (I) those that remodel the immunosuppressive tumor microenvironment (chemotherapy, PARP inhibitors, oncolytic viruses); (II) those that enhance effector cell persistence (CAR-T, CAR-NK, cytokine support); and (III) those that modulate immune checkpoint axes beyond PD-1/CTLA-4 (LAG-3, TIM-3, TIGIT). Combining ICIs with CAR-T cells, CAR-NK cells, oncolytic viruses, and exosomes has been shown to improve antitumor immune responses. This review provides a translational framework for biomarker-driven patient stratification and critically evaluates the clinical maturity of emerging platforms. Further research and clinical trials are needed to expand applicability across BC subtypes and improve patient outcomes.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"588323"},"PeriodicalIF":3.6,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13157352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147873303","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":"Efficacy, Safety, and Prognostic Factors of Dalpiciclib Combined with Endocrine Therapy After Progression on CDK4/6 Inhibitors in Patients with HR+/HER2- Advanced Breast Cancer: A Retrospective Study.","authors":"Shihan Zhou, Ru Yao, Mengqi Zhang, Mingxia Jiang, Jiaxuan Liu, Mingxiao Li, Fei Ma, Bo Pan, Qiao Li","doi":"10.2147/BCTT.S589939","DOIUrl":"10.2147/BCTT.S589939","url":null,"abstract":"<p><strong>Background: </strong>While the combination of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and endocrine therapy (ET) has established efficacy as first-line treatment for HR+/HER2- advanced breast cancer (ABC), resistance remains a critical clinical challenge. Dalpiciclib, a novel Chinese-developed CDK4/6i, has shown promising results in first-line therapy, yet data on its efficacy following progression on prior CDK4/6i is limited.</p><p><strong>Methods: </strong>This retrospective, multicenter study enrolled 58 patients with HR+/HER2- ABC who experienced disease progression after prior CDK4/6i therapy and received dalpiciclib combined with ET between July 2022 and October 2024. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and safety. Subgroup analyses were performed based on baseline clinical characteristics and prior treatment histories.</p><p><strong>Results: </strong>The median PFS was 6.3 months (95% CI: 5.2-11.0). The ORR and DCR were 8.6% and 32.8%, respectively. Patients with liver metastases exhibited significantly shorter PFS compared to those without (4.2 vs 8.0 months, <i>p</i>=0.027; HR=2.19, 95% CI: 1.08-4.43). Sequential use of dalpiciclib following progression on prior CDK4/6i progression was associated with longer PFS (8.0 vs 5.2 months, <i>p</i>=0.013; HR=0.42, 95% CI: 0.21-0.86). Patients with secondary endocrine resistance also experienced significantly longer PFS than those with primary resistance (7.2 vs 4.0 months, <i>p</i>=0.002; HR=3.28, 95% CI: 1.52-7.08). The most common grade ≥3 adverse events were neutropenia (22.4%) and leukopenia (17.2%). No patients discontinued treatment due to adverse events.</p><p><strong>Conclusion: </strong>Dalpiciclib combined with endocrine therapy demonstrates clinical efficacy and a manageable safety profile as a cross-line treatment for HR+/HER2- ABC patients who progressed on prior CDK4/6i. Subgroups including those without liver metastases, with secondary endocrine resistance, and receiving sequential CDK4/6i therapy appear to derive greater benefit. These findings support dalpiciclib as a viable cross-line therapeutic option, warranting further prospective validation.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"589939"},"PeriodicalIF":3.6,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866658","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":"Hematologic Glyco-Signatures: Emerging Blood-Based Sugar Codes Linked to Hyper-Aggressive Breast Cancer.","authors":"Emmanuel Ifeanyi Obeagu","doi":"10.2147/BCTT.S603801","DOIUrl":"10.2147/BCTT.S603801","url":null,"abstract":"<p><p>Emerging evidence suggests that aberrant glycosylation patterns in cancer are not confined to tumor tissues but are also reflected systemically in circulating blood components. In hyper-aggressive breast cancer phenotypes, including triple-negative and inflammatory subtypes, distinct alterations in glycoproteins, immunoglobulins, and extracellular vesicle-associated glycans have been reported. These hematologic glyco-signatures represent dynamic \"sugar codes\" shaped by dysregulated glycosyltransferase activity, inflammatory signaling, and tumor-host interactions. This narrative review synthesizes current knowledge on blood-based glycosylation alterations associated with aggressive breast cancer biology, emphasizing their mechanistic relevance to immune modulation, metastatic dissemination, and tumor progression. Particular attention is given to altered sialylation, fucosylation, and glycan branching patterns observed in circulating proteins, as well as their potential role in immune evasion through lectin-glycan interactions. While hematologic glyco-signatures show promise as minimally invasive biomarkers for diagnosis, prognosis, and disease monitoring, current evidence remains largely exploratory and heterogeneous. Significant challenges persist, including analytical variability, lack of standardized platforms, and limited large-scale clinical validation. Moreover, the causal versus correlative role of circulating glyco-alterations in tumor aggressiveness remains under active investigation. In conclusion, hematologic glyco-signatures represent a promising but still evolving frontier in breast cancer biomarker research. Their integration into clinical oncology will require rigorous validation, harmonization of glycomics methodologies, and comparative studies with established liquid biopsy approaches such as circulating tumor DNA and circulating tumor cells.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"603801"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13143522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833504","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":"Uncertainty-Aware Machine Learning for Predicting Axillary Lymph Node Metastasis Using Breast MRI.","authors":"Sevgi Ünal, Remzi Gürfidan","doi":"10.2147/BCTT.S599211","DOIUrl":"10.2147/BCTT.S599211","url":null,"abstract":"<p><strong>Purpose: </strong>Axillary lymph node metastasis (ALNM) is a significant prognostic factor in breast cancer and has an impact on staging, treatment and survival. The objective of this study is to create a machine learning model that will be able to predict axillary lymph node metastasis (ALNM) in a preoperative setting using breast MRI-derived and clinicopathological variables, while also achieving probability calibration and uncertainty-aware prediction for more reliable risk estimates.</p><p><strong>Patients and methods: </strong>For this retrospective single-centre study, 204 patients who underwent contrast-enhanced breast MRI from 2021 to 2024 were selected. The dataset comprised of 23 independent variables, respectively, representing demographic, clinical, radiological, histopathological, molecular characteristics along with a binary target variable indicating ALNM status. The data was split into 60% called training set, 20% calibration set, and 20% test set. Candidate models were evaluated based on ROC-AUC on the training subset that was used for screening. Subsequently, calibration was performed in a held-out calibration set, following which class-conditional conformal prediction was applied to quantify predictive uncertainty.</p><p><strong>Results: </strong>Out of all the models we evaluated, the Conformal-Calibrated Interpretable Risk Model (CCIRM) was found to be the best model, achieving a test accuracy of 0.9268, a weighted F1 score of 0.9270 and AUC of 0.937. With a precision of 0.9545 and a recall of 0.9130 in the ALNM-positive class, the model was potent. In addition to discrimination strength, the framework produces calibrated risk estimates and uncertainty-aware prediction sets that enable transparent interpretation of model outputs in clinically borderline cases.</p><p><strong>Conclusion: </strong>The proposed approach includes the model selection based on the machine learning and probability calibration, as well as conformal prediction to achieve reliability, beyond label prediction, and uncertainty-aware risk estimation for preoperative ALNM assessment. The results from this analysis suggest that CCIRM is a potential methodological framework for trustworthy clinical decision support, although the prospective and multicentre external validation should be done before it becomes applicable to the clinical setting.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"599211"},"PeriodicalIF":3.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866648","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":"Genetic Correlation of miR-423 Polymorphism rs8067576 with Progression and Prognosis of Triple-Negative Breast Cancer.","authors":"Hailing Pan, Zixin Huang, Aiping Li, Meiya Li, Yanxing Li, Ya Lin, Jiayin Cai","doi":"10.2147/BCTT.S577378","DOIUrl":"10.2147/BCTT.S577378","url":null,"abstract":"<p><strong>Background: </strong>Single nucleotide polymorphisms (SNPs) of microRNAs can affect the functional activity of microRNA, thereby relating to disease susceptibility.</p><p><strong>Objective: </strong>The study systematically examined the impact of miR-423 rs806757 SNP on triple-negative breast cancer (TNBC) risk and severity and dissected the attendant molecular mechanism.</p><p><strong>Materials and methods: </strong>Three hundred TNBC patients and 300 controls were genotyped for miR-423 rs806757, and its association with relapse-free survival (RFS) and 5-year survival was analyzed. CCK-8/Transwell assays quantified the variant's influence on tumor cell proliferation, migration and invasion. In-silico target prediction followed by GO/KEGG profiling mapped the downstream pathways.</p><p><strong>Results: </strong>A significant difference was detected in the genotype distribution of rs8067576 polymorphism between TNBC and controls. And cases harboring rs8067576 AA allele exhibited a higher prevalence of tumors >5 cm, lymph-node involvement, and higher stage (III-IV). AA genotype carriers displayed markedly reduced RFS and 5-year overall survival, and held a conspicuous rise in miR-423-5p levels compared with patients bearing alternative genotypes. Cell-based assays revealed that introducing rs8067576-A allele into tumor cells robustly boosted tumor-cell proliferation, motility, and invasiveness relative to T allele. Subsequent target prediction and pathway enrichment identified Wnt and Ras signaling as the principal downstream effector modules of miR-423-5p.</p><p><strong>Conclusion: </strong>MiR-423 rs8067576 was a susceptibility locus for TNBC and linked to earlier relapse and shorter 5-year survival. Rs8067576 boosted miR-423-5p expression, thereby enhancing tumor-cell proliferation, motility, and invasiveness.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"577378"},"PeriodicalIF":3.6,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833498","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":"Multi-Omics Characterization of ABHD12 Across Pan-Cancer and Validation of Its Role in Promoting Proliferation and Metastasis in Breast Cancer.","authors":"Jiawei Zhao, Yuting Gou, Yiyang Wang, Yongxiang Li, Haotian Ma, Yiting Xing, Haohao Peng, Chenming Guo","doi":"10.2147/BCTT.S554836","DOIUrl":"10.2147/BCTT.S554836","url":null,"abstract":"<p><strong>Purpose: </strong>ABHD12 is linked to cancer and neurodegeneration; we systematically characterized its pan-cancer role and validated its oncogenic function in breast cancer (BRCA) to guide mechanistic studies.</p><p><strong>Methods: </strong>We integrated multi-omics data from TCGA, GTEx, and various public platforms to analyze expression, prognosis, genetic variations, methylation, immune infiltration, and drug resistance. In qRT-PCR, Western blot, functional assays (CCK-8, wound healing, colony formation), and a nude mouse xenograft model, were conducted to validate ABHD12's role in BRCA.</p><p><strong>Results: </strong>ABHD12 was significantly upregulated at both mRNA and protein levels across multiple cancers. High expression correlated with poorer overall survival in BRCA, GBM, LGG, LIHC, and UVM. It demonstrated strong to moderate diagnostic value. ABHD12 expression was associated with copy number variations (CNVs) across 23 cancers, but not with methylation. It also correlated with immune cell infiltration (especially with macrophage), tumor mutational burden, neoantigens, microsatellite instability, and immune-related genes in certain cancers, and was potentially linked to resistance to multiple chemotherapeutics. KEGG analysis indicated that ABHD12 may play a potential role in the AMPK pathway. In BRCA, ABHD12 was higher in tumors than normal tissues. Functional studies showed ABHD12 enhanced proliferation, invasion, and migration, while silencing suppressed these traits. In vivo, ABHD12-overexpressing cells formed larger tumors, confirming its tumor-promoting role.</p><p><strong>Conclusion: </strong>ABHD12 may act as an oncogene across multiple cancers, linked to poor prognosis, diagnostic potential, chemotherapy resistance, and immunotherapy response. Its dysregulation is driven by CNVs rather than promoter methylation. ABHD12 might modulate macrophage polarization via the AMPK signaling pathway, leading to the remodeling of the tumor immune microenvironment. In vitro and vivo studies confirm its pro-tumorigenic role in BRCA, highlighting ABHD12 as a multifunctional biomarker and a molecular nexus linking lipid metabolism, immunity, and treatment resistance-warranting further study.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"554836"},"PeriodicalIF":3.6,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135767/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833453","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":"Clinical Relevance of USP44 Expression and DNA Methylation Status in Breast Cancer Cell Lines, Tumor Tissues, and Circulating Tumor DNA.","authors":"Kee Tae Park, Na-Rang Lee, Young Ju Jeong","doi":"10.2147/BCTT.S599533","DOIUrl":"10.2147/BCTT.S599533","url":null,"abstract":"<p><strong>Purpose: </strong>Ubiquitin-specific peptidase 44 (USP44), a deubiquitinating enzyme involved in chromosomal stability and cell cycle control, has been proposed as a potential biomarker and a therapeutic target in various cancers. However, its expression and epigenetic regulation in breast cancer remain understudied. This study investigated USP44 expression and DNA methylation status in breast cancer cell lines, breast cancer tissues and circulating tumor DNA (ctDNA), and their association with clinicopathological features.</p><p><strong>Patients and methods: </strong>USP44 expression was assessed by quantitative reverse transcription-polymerase chain reaction in cell lines, and by immunohistochemistry in breast tissues including 33 breast cancers and 13 benign breast lesions. DNA methylation status of USP44 was analyzed by pyrosequencing in tissue samples, and by methylation-specific PCR in ctDNA and cell lines. Associations with clinicopathological parameters were statistically evaluated.</p><p><strong>Results: </strong>USP44 expression varied among breast cancer cell lines, with highest levels in the triple-negative breast cancer MDA-MB-231, corresponding to an unmethylated USP44 promoter. The positive expression rate of USP44 was 69.7% in breast cancer tissues. USP44 expression in breast cancer tissues did not differ significantly with that of benign tissues, but was associated with age ≥60 years and inversely correlated with presence of fibrotic focus. Mean methylation frequency was 43.7 ± 13.2% in breast cancer tissues, and ctDNA methylation was detected in 65.7% of breast cancer patients. Methylation status in ctDNA did not correlate with tissue methylation. Higher tissue USP44 methylation frequency was significantly associated with progesterone receptor positivity, HER2 overexpression and molecular subtype of breast cancer.</p><p><strong>Conclusion: </strong>USP44 gene expression and DNA methylation status were associated with distinct clinicopathological features in breast cancer. These findings suggest complex epigenetic regulation of USP44 and its biological relevance in breast cancer. Given the limited sample size and exploratory design, further studies in larger independent cohorts are required to validate the potential role of USP44 as an epigenetic biomarker.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"599533"},"PeriodicalIF":3.6,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13135340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810991","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":"Novel Insights into the Oncogenic Role and Clinical Significance of ORC6L in Breast Cancer.","authors":"Xiaohan Jiang, Shuaijie Wang, Qiufang Wei, Yuzhong Yang, Yan Chen, Shaohua Chen","doi":"10.2147/BCTT.S586715","DOIUrl":"10.2147/BCTT.S586715","url":null,"abstract":"<p><strong>Purpose: </strong>ORC6L has been implicated in various malignancies, and our preliminary bioinformatic analysis revealed its significant overexpression in breast cancer specimens. This study aims to investigate the biological functions and clinicopathological significance of ORC6L in breast cancer, and to evaluate its potential as a prognostic biomarker and therapeutic target.</p><p><strong>Methods: </strong>ORC6L protein expression in breast cancer tissues was assessed via immunohistochemistry, followed by statistical analysis to determine its diagnostic and prognostic significance. To investigate the biological functions of ORC6L, a series of in vitro experiments were conducted in breast cancer cell lines. Cell proliferation was measured using colony formation, CCK-8, and EdU assays. Apoptosis was evaluated by flow cytometry. Cell migration and invasion were assessed via wound-healing and transwell assays, respectively.</p><p><strong>Results: </strong>ORC6L expression was markedly elevated in breast cancer tissues compared with adjacent non-tumor tissues. This elevated expression demonstrated high diagnostic value and was positively correlated with higher pathological grade. Moreover, ORC6L emerged as an independent predictor of poor survival outcomes in breast cancer patients. In vitro functional assays further revealed that ORC6L overexpression promoted proliferation, suppressed apoptosis, and enhanced migration, whereas ORC6L knockdown effectively inhibited proliferation, induced apoptosis, and attenuated migration.</p><p><strong>Conclusion: </strong>ORC6L serves as a key driver of breast cancer progression, supporting its potential as a therapeutic target, though its independent prognostic value requires further validation.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"586715"},"PeriodicalIF":3.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13109065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762060","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":"From Axillary Lymph Node Dissection to Sentinel Node Biopsy in Breast Cancer: A 23-Year Population-Based Large-Sample Study with Long-Term Survival Outcomes.","authors":"Lucia Mangone, Francesco Marinelli, Isabella Bisceglia, Maria Barbara Braghiroli, Antonino Neri, Fortunato Morabito, Carmine Pinto, Moira Ragazzi, Guglielmo Ferrari, Saverio Coiro, Eugenio Cenini","doi":"10.2147/BCTT.S573154","DOIUrl":"10.2147/BCTT.S573154","url":null,"abstract":"<p><strong>Purpose: </strong>Axillary surgery in breast cancer has progressively evolved over the past decades toward less invasive approaches.</p><p><strong>Patients and methods: </strong>This population-based study analyzed 10,955 women diagnosed with invasive breast cancer between 2000 and 2022 in Reggio Emilia, Italy, to assess long-term trends in axillary management.</p><p><strong>Results: </strong>A marked decline in axillary lymph node dissection (ALND) was observed-from 47.9% in 2000-2004 to 18.1% in 2017-2022-with a parallel increase in sentinel lymph node biopsy (SLNB) from 43.8% to 74.7%. The shift was particularly pronounced in stage I tumors, where ALND dropped from 44.7% to 2.9%. Overall survival at 15 years was significantly higher in the SLNB group (78%) compared to the ALND group (72%). These results align with major clinical trials (e.g. ACOSOG Z0011, SINODAR-ONE), confirming their applicability in unselected populations. Although ALND remained more frequent in patients with larger tumors or undergoing mastectomy, its role has substantially diminished.</p><p><strong>Conclusion: </strong>Our findings reinforce the safety and effectiveness of conservative axillary approaches and reflect their successful implementation in real-world practice. Further research should address the impact of these trends on quality of life and incorporate additional data on radiotherapy and tumor biology to guide future surgical decision-making.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"573154"},"PeriodicalIF":3.6,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13098557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762148","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}