Breast Cancer : Targets and Therapy最新文献

{"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":"https://doi.org/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":3.4,"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":"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":"https://doi.org/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":3.4,"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":"https://doi.org/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":3.4,"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":"https://doi.org/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":3.4,"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":"https://doi.org/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":3.4,"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":"https://doi.org/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":3.4,"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}

{"title":"LINC01128 Affects Triple-Negative Breast Cancer Progression Through Targeting miR-32-5p.","authors":"Min Xiong, Quanjun Yang, Le Cheng, Lili Yu, Yili Hu","doi":"10.2147/BCTT.S596228","DOIUrl":"https://doi.org/10.2147/BCTT.S596228","url":null,"abstract":"<p><strong>Objective: </strong>To clarify the expression and clinical significance of LINC01128 in triple-negative breast cancer (TNBC), investigate whether it regulates the biological behaviors of TNBC cells by targeting miR-32-5p via the ceRNA mechanism, and explore new therapeutic targets.</p><p><strong>Methods: </strong>Tumor tissues and corresponding adjacent normal tissues from 76 TNBC patients were collected, and the patients' clinicopathological data were gathered. Experiments were conducted using the human normal breast epithelial cell line MCF-12F and multiple TNBC cell lines. Quantitative real-time PCR (qPCR) was used to detect the relative expressions of LINC01128 and miR-32-5p; dual-luciferase reporter assay was performed to verify the targeted binding relationship between the two. CCK-8 assay, flow cytometry, and Transwell assay were used to detect cell proliferation, apoptosis, and migration abilities, respectively. Target gene prediction and GO/KEGG enrichment analyses were carried out by combining databases such as miRDB and miRWalk.</p><p><strong>Results: </strong>LINC01128 was highly expressed in TNBC tissues and cells (P<0.01), and its high expression was an independent risk factor for advanced TNBC (OR=6.635, P=0.001). miR-32-5p was lowly expressed in TNBC (P<0.01) and showed a significant negative correlation with LINC01128 (r=-0.699, P<0.001), with a direct targeted binding between the two. LINC01128 promoted TNBC cell proliferation and migration and inhibited apoptosis by suppressing miR-32-5p (all P<0.01). The target genes of miR-32-5p were enriched in tumor-related pathways.</p><p><strong>Conclusion: </strong>LINC01128 is highly expressed in TNBC and promotes tumor progression by targeting and suppressing miR-32-5p via the ceRNA mechanism, which can serve as a potential molecular marker and therapeutic target for TNBC.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"596228"},"PeriodicalIF":3.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13096830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762132","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":"HER2 Overexpression in Invasive Breast Carcinoma in the Democratic Republic of Congo and its Association with Selected Clinicopathological Characteristics.","authors":"Guy Ilunga Nday, Manix Ilunga Banza, Anastasie Ngalula Umpungu, Michel Kabamba Nzaji, Jules Ngwe Thaba Moyambe","doi":"10.2147/BCTT.S600288","DOIUrl":"https://doi.org/10.2147/BCTT.S600288","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is a heterogeneous disease and HER2 overexpression identifies a subgroup of tumors associated with aggressive behavior and targeted therapy response. Although HER2 expression has been widely studied worldwide and in some African countries, data remain limited in the Democratic Republic of the Congo, where access to molecular diagnostic techniques is still restricted.</p><p><strong>Objective: </strong>This study aimed to determine the frequency of HER2 protein overexpression and its association with clinicopathological characteristics of breast carcinoma in the Democratic Republic of the Congo in order to provide local evidence to support diagnostic and therapeutic strategies.</p><p><strong>Methods: </strong>We conducted a cross-sectional analytical study from 2014 to 2016 in Kinshasa and Lubumbashi including 86 invasive breast carcinoma cases. HER2 expression was assessed by immunohistochemistry and scored according to standard guidelines. Associations were analyzed using odds ratios with 95% confidence intervals.</p><p><strong>Results: </strong>HER2 overexpression was observed in 25.6% of cases. No statistically significant association was found between HER2 status and age, tumor size, histological type, tumor grade, or estrogen receptor status. The absence of statistical significance may be related to the limited sample size.</p><p><strong>Conclusion: </strong>Approximately one quarter of breast carcinomas showed HER2 overexpression in this Congolese population. These findings support the importance of routine HER2 testing in breast cancer management in resource-limited settings. Although no statistically significant associations were found, this study provides additional data on HER2 expression in the Congolese context and highlights the need for larger studies with longer study periods to better assess clinicopathological associations.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"600288"},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728292","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":"Capecitabine versus Paclitaxel After CDK4/6 Inhibitor Progression in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: A Real-World Study.","authors":"Zeliha Birsin, Ali Kaan Güren, Vali Aliyev, Murad Guliyev, Seda Jeral, Selin Cebeci, Emir Çerme, Murat Günaltılı, Hamza Abbasov, Ebru Çiçek, Süheyla Atak, Murat Sarı, Nebi Serkan Demirci, Özkan Alan","doi":"10.2147/BCTT.S598598","DOIUrl":"https://doi.org/10.2147/BCTT.S598598","url":null,"abstract":"<p><strong>Background: </strong>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy represent the standard first-line treatment for hormone receptor-positive (HR+), HER2-negative metastatic breast cancer. However, optimal chemotherapy selection after progression on CDK4/6i remains unclear. This study aimed to compare the clinical outcomes of capecitabine versus paclitaxel in a real-world post-CDK4/6i setting.</p><p><strong>Methods: </strong>This retrospective two-center study included HR+/HER2- metastatic breast cancer patients who experienced disease progression after CDK4/6i therapy and subsequently received either capecitabine or paclitaxel. Paclitaxel was administered at a dose of 80 mg/m² weekly, while capecitabine was given at 1000-1250 mg/m² twice daily on days 1-14 of a 21-day cycle. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox regression analyses.</p><p><strong>Results: </strong>A total of 115 patients were included, of whom 68 (59%) received capecitabine and 47 (41%) received paclitaxel. Baseline clinicopathological characteristics were comparable between the two groups. The median follow-up was 48.3 months. Median PFS was 5.45 months in the capecitabine group and 6.53 months in the paclitaxel group (p = 0.622). Median OS was 42.2 and 43.1 months, respectively (p = 0.299). Treatment type was not independently associated either PFS or OS. Visceral metastasis after CDK4/6i progression independently predicted shorter PFS (HR 1.62, p = 0.042), whereas higher tumor grade was associated with inferior OS (HR 1.82, p = 0.018). Treatment-related toxicities differed between regimens: paclitaxel was predominantly associated with neuropathy and hematologic toxicity, whereas capecitabine was primarily associated with hand-foot syndrome and gastrointestinal toxicity.</p><p><strong>Conclusion: </strong>Capecitabine and paclitaxel demonstrated comparable efficacy after CDK4/6i progression, with no significant differences in PFS or OS. Given their distinct toxicity profiles, treatment selection should be individualized according to patient characteristics and tolerability.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"598598"},"PeriodicalIF":3.4,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13092254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147728315","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":"Single-Cell Profiling Reveals a Treg-Rich, NK Cell-Depleted Immune Microenvironment in Triple-Negative Breast Cancer with High-Glucocorticoid Receptor Expression.","authors":"Joshua Behar, Christine Shiang, Deniz Nesli Dolcen, Lynda B Bennett, Andrew W DeVilbiss, Margarite D Matossian, Isaac S Chan, Rita Nanda, Suzanne D Conzen, John T Lafin","doi":"10.2147/BCTT.S569936","DOIUrl":"10.2147/BCTT.S569936","url":null,"abstract":"<p><strong>Purpose: </strong>Analyses of patients with early-stage, treatment-naïve triple-negative breast cancer (TNBC) have demonstrated that high glucocorticoid receptor (GR) expression in primary tumors is associated with poor prognosis. We previously observed that GR-high primary TNBCs exhibited significantly increased numbers of tumor-infiltrating regulatory T cells (Tregs) compared with GR-low tumors. To further investigate GR-associated immunologic features, we leveraged imaging mass cytometry (IMC) to profile additional immune cell phenotypes and spatial architecture in GR-high versus GR-low primary TNBC.</p><p><strong>Patients and methods: </strong>Tumor-infiltrating immune cells were profiled in formalin-fixed paraffin-embedded (FFPE) core biopsies from five untreated GR-high and four GR-low TNBC tumors using IMC with a 21-antibody panel. Regions of interest (ROI) were selected within pan-cytokeratin-positive tumor nests. Data underwent unsupervised clustering, and cell types were identified based on protein expression profiles. Analyses compared cell-type abundance and spatial interactions in GR-high versus GR-low tumors.</p><p><strong>Results: </strong>GR-high tumors exhibited significantly greater Treg infiltration within tumor nests than GR-low tumors. GR-high TNBC also showed a comparatively greater abundance of activated memory CD8+ T cells, cytotoxic CD4+ T cells, and effector memory CD4+ T cells. In contrast, GR-low tumors exhibited relatively greater representation of HLA-ABC-positive (HLA-ABC+) cancer cells as well as early-activated dendritic cells (DCs) and natural killer (NK) cells. Spatial analysis revealed that Tregs in GR-high tumors colocalized more frequently with proliferating tumor cells relative to Tregs in GR-low tumors. NK cells in GR-high tumors displayed relatively less colocalization with proliferating tumor cells.</p><p><strong>Conclusion: </strong>Compared with GR-low disease, treatment-naïve GR-high primary TNBC exhibits a more immunosuppressive tumor microenvironment characterized by greater Treg density, closer Treg-cancer cell proximity, reduced NK cell infiltration, impaired immune surveillance, and decreased abundance of HLA-ABC+ cancer cells. These findings implicate TNBC cell GR signaling as immunosuppressive, likely through mechanisms resulting in both differential immune cell enrichment and altered spatial organization.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"569936"},"PeriodicalIF":3.4,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13091597/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721603","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}