Breast Cancer : Targets and Therapy最新文献

{"title":"Bystin is a Prognosis and Immune Biomarker: From Pan-Cancer Analysis to Validation in Breast Cancer.","authors":"Xiyidan Aimaiti, Yiyang Wang, Dilimulati Ismtula, Yongxiang Li, Haotian Ma, Junyi Wang, Dilraba Elihamu, Chenming Guo","doi":"10.2147/BCTT.S537429","DOIUrl":"10.2147/BCTT.S537429","url":null,"abstract":"<p><strong>Introduction: </strong>The Bystin gene (BYSL) contributes to cancer development and is a probable therapeutic target in cancer therapy. However, no systematic studies have been conducted on BYSL value in pan-cancer diagnosis, prognosis, and immunology.</p><p><strong>Methods: </strong>We performed a pan-cancer analysis of BYSL using TCGA, GEO, and other databases to assess its expression, clinical significance, genetic variants, methylation, and immune correlation. Enrichment analysis was applied to predict BYSL-related pathways. We analyzed BYSL protein levels in corresponding breast cancer (BRCA) tissue samples to validate our findings using Western blot assays. A tissue microarray was deployed to verify BYSL expression in BRCA tissues by immunohistochemical staining. Moreover, we comprehensively analyzed the function of BYSL in BRCA initiation and development through CCK-8, transwell invasion, migration assays, and cell scratch assays for migration ability assessment.</p><p><strong>Results: </strong>Through the study, BYSL was significantly overexpressed in the majority of cancers relative to normal tissues, with different expression patterns at different clinicopathological stages. In most cancer types, BYSL exhibits moderate to high diagnostic value, and overexpressed BYSL represents an independent prognosis factor in patients having BRCA, HNSC, KICH, LIHC, OV, and SARC cancers. Mutations in BYSL are distributed in most cancers and are related to prognosis. Most tumors have elevated levels of m6A methylation compared to normal tissues, while their promoter regions exhibit low levels of methylation. Additionally, BYSL expression displayed a positive correlation with MDSC immune infiltration. Further enrichment analysis showed the involvement of BYSL in important biological processes (BP), In addition, BYSL was overexpressed in BRCA tissues and promoted their proliferation, invasion, and migration compared to matched normal breast tissues.</p><p><strong>Discussion: </strong>Our study showed that BYSL is an important biological indicator for predicting pan-cancer survival outcomes and immune characteristics and elucidated BYSL expression and role in BRCA, which highlights its therapeutic potential in BRCA.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"755-779"},"PeriodicalIF":3.4,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12404263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991514","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":"Age and Education Influencing Willingness in Men to Recommend Breast Cancer Screening: A Comparative Study of University Personnel and Clinical Attendees.","authors":"Suleyman Buyukasik, Burak Kankaya, Yusuf Emre Altundal, Mustafa Ozgul, Fatemeh Atashbari, Aisha Abshir Hussain Osman, Halil Alis, Selin Kapan","doi":"10.2147/BCTT.S533079","DOIUrl":"10.2147/BCTT.S533079","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer is a major global health concern. In some societies, male family members influence women's healthcare decisions, yet their awareness and attitudes toward breast cancer screening remain poorly understood. Our research aimed to analyze awareness, knowledge, and willingness to recommend breast cancer screening among men from two distinct populations, and to examine how age and educational level influence willingness to recommend breast examinations for female family members.</p><p><strong>Patients and methods: </strong>This prospective cross-sectional survey study included male academic staff at a university (University Personnel Group, n=105) and male patients visiting a hospital policlinic with non-breast-related complaints along with their male companions (Clinical Attendee Group, n=100). A 10-item structured questionnaire assessed demographics, knowledge about breast cancer, and attitudes toward mammography screening using statistical analysis.</p><p><strong>Results: </strong>Both groups demonstrated similar knowledge levels regarding breast cancer frequency in women (~55%), male breast cancer occurrence (~45%), and annual mammography necessity (~52%). The clinical attendee group showed significantly greater willingness to recommend breast examinations compared to the university personnel group (94.0% vs 74.3%, p<0.001). In the clinical attendee group, willingness increased with age (88.9% in ages 15-25 to 100% in ages 40+), showing a significant positive trend (p<0.05). The university personnel group exhibited peak willingness (87.1%) in the 25-40 age group, with lower rates in other age categories. Educational status strongly influenced willingness in the university personnel group, increasing from 33.3% at high school level to 87.8% at Master's/Ph.D. level, while the clinical attendee group maintained high willingness (91.7-100%) across all education levels.</p><p><strong>Conclusion: </strong>Our findings show patterns of breast cancer awareness and screening recommendation willingness between clinical attendees and university personnel. While basic knowledge about breast cancer was similar, willingness to recommend screening differed significantly, with age and education having differential impacts between groups.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"741-754"},"PeriodicalIF":3.4,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12396239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942640","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":"Safety Profile and Predictors of Adverse Events of Incadronate Disodium in Treating Breast Cancer Patients with Bone Metastases: A Retrospective Study.","authors":"Shihan Zhou, Mingxia Jiang, Jiaxuan Liu, Mengqi Zhang, Mingxiao Li, Maiyue He, Nilupai Abudureheiyimu, Wenna Wang, Xiuwen Guan, Fei Ma, Binghe Xu, Qiao Li","doi":"10.2147/BCTT.S523392","DOIUrl":"10.2147/BCTT.S523392","url":null,"abstract":"<p><strong>Purpose: </strong>Bone metastasis is a common complication in advanced breast cancer. Bisphosphonates like incadronate disodium have shown potential in reducing bone resorption and skeletal-related events. We therefore performed a retrospective study to evaluate the safety profile of incadronate disodium in breast cancer patients with bone metastases.</p><p><strong>Patients and methods: </strong>This retrospective study was conducted involving 84 breast cancer patients with bone metastases who received incadronate disodium treatment between February 2022 and August 2024 in our center. The primary endpoint was the incidence of dental-related issues and acute phase reactions, with an analysis of the associated risk factors. The secondary endpoint was the incidence of other adverse events. Adverse events were recorded during treatment and within 90 days post-treatment.</p><p><strong>Results: </strong>Dental-related issues were observed in 33.3% of patients and only one (1.2%) developed medication-related osteonecrosis of the jaw. Higher risk was significantly associated with prolonged treatment duration (OR = 4.33, 95% CI:1.21-15.50), secondary bone metastases (OR = 6.3, 95% CI:1.58-25.00), and lower hemoglobin levels (OR = 4.16, 95% CI:1.31-13.2) at multivariate analysis. 26.2% patients occurred acute phase reactions. Higher medication doses (OR = 1.41, 95% CI:1.07-2.05), multiple metastatic sites (OR = 4.22, 95% CI:1.39-15.89) and lower hemoglobin levels (OR = 3.27, 95% CI:1.21-9.22) were significant in univariate analysis, but not in multivariate analysis. Rare adverse effects included renal dysfunction (1.2%) and hypocalcemia (4.76%).</p><p><strong>Conclusion: </strong>Incadronate disodium demonstrates a favorable safety profile for treating bone metastases in breast cancer patients. Identified risk factors, such as prolonged treatment duration and lower hemoglobin levels, highlight the need for intensified dental health management and personalized treatment strategies.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"727-739"},"PeriodicalIF":3.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12375327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942623","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":"Predicting Human Epidermal Growth Factor Receptor 2 Expression in Breast Cancer Based on Radiomics of MRI Habitat and US.","authors":"Zikai Lin, Fangyi Huang, Liyan Wei, Xinhong Liao, Yong Gao","doi":"10.2147/BCTT.S535697","DOIUrl":"10.2147/BCTT.S535697","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to predict human epidermal growth factor receptor-2 (HER-2) expression in breast cancer based on radiomics of magnetic resonance imaging (MRI) habitat and ultrasound (US).</p><p><strong>Patients and methods: </strong>This retrospective study included 182 breast cancer patients confirmed by pathology from May 25, 2019 to April 15, 2025. The data set was randomly divided into a training set (n=145) and a testing set (n=37) with an 8:2 ratio. All patients underwent MRI and US before surgery. Volumes of interest were delineated on the second phase of dynamic contrast-enhanced T1-weighted imaging, which were clustered into different habitat regions via K-means clustering. Feature selection was using Spearman correlation, greedy recursive elimination strategy, least absolute shrinkage and selection operator regression. Models based on extremely randomized trees were developed using radiomics features extracted from MRI habitats, or from regions of interest on US. A clinical model was developed based on baseline data, followed by stacking the best habitat model and US model, as well as a combination of the best habitat, US, and clinical models. Model performance was evaluated by areas under the curve (AUCs) and integrated discrimination improvement (IDI). The interpretability of the best habitat model and US model was using Shapley Additive exPlanations analysis.</p><p><strong>Results: </strong>Model_H1__{multi-parametric} was selected as the best habitat model (AUC was 0.880 and 0.801 in the training set and testing set). Model__H1+US+Cli (AUC was 0.945 and 0.835 in the training set and testing set) outperformed Model_H1__{multi-parametric}, the US model and the clinical model. The IDI analysis demonstrated further improvement by Model__H1+US+Cli.</p><p><strong>Conclusion: </strong>A combined model based on multi-parametric MRI habitat radiomics, US imaging radiomics, and clinical features can effectively predict HER-2 expression status in breast cancer.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"711-725"},"PeriodicalIF":3.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12364004/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144942587","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":"Mechanisms and Management of Albumin-Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer.","authors":"Xingchao Xu, Qinyu Han, Shi Qiu, Shang Gao, Chuanxin Ren, Xiangqi Li","doi":"10.2147/BCTT.S531877","DOIUrl":"10.2147/BCTT.S531877","url":null,"abstract":"<p><p>Breast cancer incidence continues to rise globally, with molecular subtyping now playing a critical role in prognosis and treatment selection. The main subtypes-Luminal A, Luminal B, HER2-enriched, and triple-negative breast cancer (TNBC)-exhibit distinct clinical behaviors and treatment responses, with respective molecular characteristics. Chemotherapy plays a pivotal role in the comprehensive treatment of breast cancer, being widely used in neoadjuvant, adjuvant, and metastatic systemic therapy. Albumin-Paclitaxel based regimens remain the cornerstone of clinical treatment, particularly for highly aggressive subtypes like triple-negative breast cancer (TNBC) and HER2-positive breast cancer. However, 30-60% of breast cancer patients receiving chemotherapy develop chemotherapy-induced peripheral neuropathy (CIPN). Approximately 35% experience severe (≥grade 2) symptoms, often requiring dose modification or treatment discontinuation. Albumin-Paclitaxel's neurotoxicity primarily involves two mechanisms: microtubule stabilization disruption causing axonal transport impairment, and sensory neuron mitochondrial dysfunction. For younger patients, this presents dual clinical challenges: controlling tumor progression while managing neuropathic pain and functional impairment that significantly affect quality of life and work capacity. Treatments are constantly evolving and currently, the most effective treatments (eg duloxetine, cold therapy). Understanding CIPN pathogenesis, diagnostic approaches, and developing effective prevention/treatment strategies is clinically crucial. This maintains treatment adherence and efficacy while improving long-term quality of life for breast cancer patients.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"693-709"},"PeriodicalIF":3.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12358126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871477","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":"Late Breast Cancer Recurrence Prediction: The Role of CTS5 and Progesterone Receptor Status.","authors":"Giselle De Souza Carvalho, Daniel Musse Gomes, Gustavo De Oliveira Bretas, Victor Braga Gondim Teixeira, José Bines","doi":"10.2147/BCTT.S512760","DOIUrl":"10.2147/BCTT.S512760","url":null,"abstract":"<p><strong>Purpose: </strong>The current study aimed to assess the recurrence rate in hormone-receptor positive, HER2 negative (HR-positive/HER2-negative) breast cancer patients from a single center in Brazil and compare it with estimates provided by the Clinical Treatment Score post-five years (CTS5).</p><p><strong>Methods: </strong>This study comprised a retrospective analysis of patients from a national cancer center database, which began treatment between 2007 and 2008 and had no evidence of recurrence after five years of follow-up. All patients had confirmed diagnosis of HR-positive/HER2-negative early breast cancer. Disease Free-Survival (DFS) according to each CTS5 risk subgroup was the main outcome.</p><p><strong>Results: </strong>A total of 162 patients were enrolled, 26.5% being premenopausal. The mean age at diagnosis was 60.1 years (49.8─71.6). Tumor stage: I (43.8%) and II (56.2%). Endocrine therapy consisted mainly of tamoxifen (88.0%). About 39.5%, 39.5%, and 21.0% of patients were in the low, intermediate, and high-risk (L/I/H) subgroups according to CTS5, respectively. Progesterone-receptor (PR) was ≥20% in 71.0% of tumors and 77.0%, 69.0%, and 65.0% in the L/I/H subgroups, respectively. The median follow-up was 88.9 months. DFS at 5 years (10 years since the beginning of endocrine therapy) was 100%, 96.3% (95% CI, 89.4%─100%) and 68.2% (95% CI, 48.7%─95.5%) in the L/I/H subgroups, respectively. PR was an independent prognostic factor for late recurrence in intermediate- (p=0.022) and high-risk (p=0.003) subgroup patients according to CTS5.</p><p><strong>Conclusion: </strong>CTS5 performed well in the high-risk subset of patients from a wider population, including premenopausal women. The progesterone receptor was an independent prognostic factor for DFS in intermediate- and high-risk populations and should be further investigated in prospective multicenter studies.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"683-691"},"PeriodicalIF":3.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144774605","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":"Effectiveness of a Care Plan Based on the Multi-Theory Model in Reducing Fear of Disease Progression and Improving Quality of Life in Breast Cancer Patients: A Randomized Controlled Trial.","authors":"Jiajia Zhang, Jiaru Zhuang, Xian Chen, Tianyu Chu, Qian Zhang, Linlin Ma, Hui Zhou, Yibo Wu, Ling Chen","doi":"10.2147/BCTT.S534595","DOIUrl":"10.2147/BCTT.S534595","url":null,"abstract":"<p><strong>Purpose: </strong>Fear of progression has become a prominent mental health problem. Our research aimed to evaluate the effectiveness of a care plan based on the Multi-Theory Model of health behavior change in reducing fear of progression in breast cancer patients undergoing adjuvant chemotherapy.</p><p><strong>Patients and methods: </strong>This randomized controlled trial enrolled 108 eligible participants receiving adjuvant chemotherapy at Jiangnan University Affiliated Hospital between May and December 2024. Routine care was administered to the control group, while the intervention group received the multi-theoretical model-based nursing intervention program integrated with general nursing. The evaluation time points included pre-intervention, immediately post-intervention (after 6 weeks), and 1-month post-intervention. Data were analyzed using Fisher's exact test or chi-square test, Mann-Whitney <i>U</i>-test, independent samples <i>t</i>-test, generalized estimating equations, or repeated measures ANOVA.</p><p><strong>Results: </strong>At various post-intervention assessments, the Multi-Theory Model group demonstrated significantly lower fear of progression scores along with higher self-management efficacy and quality of life scores, compared to the control group (<i>p</i> < 0.05). There were time, between-group, and interaction effects for the differences in the total scores of quality of life, self-management efficacy, and fear of progression between the two groups of participants (<i>p</i> < 0.05).</p><p><strong>Conclusion: </strong>A nursing program grounded in the multi-theoretical model reduced the level of fear of progression, and improved quality of life and self-management efficacy in patients with breast cancer undergoing postoperative chemotherapy. These findings can provide a reference for psychological interventions in clinical settings for breast cancer patients.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"653-667"},"PeriodicalIF":3.4,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741086","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 Prognosis and Nomograms for Hormone Receptor-Positive and Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Patients Treated with Palbociclib and Endocrine Therapy.","authors":"Shubin Song, Luhao Sun, Xiaoyu Liu, Liang Zhang, Chao Li, Zhaoyun Liu, Fengzhen Liu, Zhiyong Yu","doi":"10.2147/BCTT.S523199","DOIUrl":"10.2147/BCTT.S523199","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to analyze factors affecting the prognosis of patients with hormone receptor-positive (HR+) and human epidermal growth factor 2-negative (HER2-) metastatic breast cancer (MBC) treated with palbociclib and endocrine therapy (ET).</p><p><strong>Methods: </strong>Patients with HR+/HER2- MBC who were treated with palbociclib plus ET between January 2019 and December 2020 at Shandong Cancer Hospital were recruited. Clinicopathological data, treatment outcomes, and survival were from electronic medical system and telephone follow-up.</p><p><strong>Results: </strong>A total of 90 eligible patients were recruited in this study; 55 (61.11%) patients preferred chemotherapy as first treatment, and 35 (38.89%) preferred ET as first treatment. The percentages for 1st, 2nd line, and ≥3 lines applying palbociclib were 17.78%, 16.66%, and 65.56%, respectively. In the univariate analysis, multiple factors influenced the primary overall survival (pOS, from initial diagnosis of BC to death), progression-free survival (PFS), and mOS (from diagnosis of metastasis to death). Meanwhile in the multivariate analysis, pPR (progesterone receptor of primary tumor) and prior ET response were independent risk factors for pOS, PFS, and mOS. Lower pPR and prior ET resistance predicted poorer pOS, PFS, and mOS in HR+/HER2- MBC patients. Number of lines of palbociclib application was an independent risk factor for pOS and mOS and presented higher points both in the pOS and mOS nomograms, meaning that palbociclib had a more significant impact on pOS and mOS compared to other factors. The nomograms showed excellent discrimination and prediction accuracy with area under curves (AUC) of 0.974 for pOS, 0.627 for PFS, and 0.881 for mOS, respectively.</p><p><strong>Conclusion: </strong>This real-world single-center study of patients with HR+/HER2- MBC showed that early application of palbociclib combined with ET may bring better PFS, but not pOS and mOS. pPR and prior ET response were independent risk factors affecting prognosis.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"669-681"},"PeriodicalIF":3.4,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12303772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144741174","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":"N2 Neutrophils and Tumor Progression in Breast Cancer: Molecular Pathways and Implications.","authors":"Emmanuel Ifeanyi Obeagu","doi":"10.2147/BCTT.S542787","DOIUrl":"10.2147/BCTT.S542787","url":null,"abstract":"<p><p>Neutrophils, traditionally viewed as first-line defenders in innate immunity, are increasingly recognized for their dualistic roles in cancer. In breast cancer, a distinct subset known as N2 neutrophils exhibits pro-tumorigenic activity, facilitating angiogenesis, immune suppression, and metastasis. This narrative review synthesizes current evidence on the molecular mechanisms underlying N2 polarization-focusing on key pathways such as TGF-β, STAT3/6, and hypoxia-mediated signaling-and their implications in breast cancer progression. We further explore how N2 neutrophils interact with other immune cells within the tumor microenvironment to promote an immunosuppressive milieu. A unique contribution of this review lies in its integration of emerging single-cell and flow cytometry data to underscore neutrophil plasticity and subtype-specific differences in neutrophil activity across breast cancer variants. Therapeutic strategies targeting N2 neutrophils are critically examined, including small-molecule inhibitors, cytokine blockade, and neutrophil-targeted nanomedicine. However, major challenges persist-most notably the difficulty in selectively depleting or reprogramming N2 neutrophils without compromising essential antimicrobial functions. Additionally, the lack of validated N2-specific markers in clinical samples limits translational progress. Addressing these gaps is crucial for the development of safe, effective immunomodulatory therapies in breast cancer.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"639-651"},"PeriodicalIF":3.4,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12296999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144727939","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":"Peripheral TNF-α and CD8⁺/CD28⁺ T Lymphocytes as Alternatives for PD-L1 Prediction in Breast Cancer Tumor Microenvironment: Stratified by Neoadjuvant Therapy.","authors":"Jiangping Wu, Xin Ou, Keyu Yuan, Feng Shi, Quan Zhou, Suzhen Lyu, Yanping Li, Yanjie Zhao, Yu Cao, Jianping Sun, Qingkun Song","doi":"10.2147/BCTT.S532688","DOIUrl":"10.2147/BCTT.S532688","url":null,"abstract":"<p><strong>Background: </strong>Programmed death-ligand 1 (PD-L1) is an immunotherapy target; however, its detection is based on biopsy tissues, and repeated biopsies present clinical challenges. This study aimed to explore peripheral blood-based alternatives to PD-L1 tissue detection in breast cancer (BC), particularly stratification by neoadjuvant therapy (NAT).</p><p><strong>Methods: </strong>A total of 134 cases were recruited, the peripheral lymphocyte subtypes and cytokines were detected by flow cytometry and PD-L1 expression in tumor microenvironment (TME) was detected by immunohistochemistry and assessed by two qualified pathologists.</p><p><strong>Results: </strong>The patients with positive PD-L1 expression had peripheral CD8⁺/CD28⁺ T lymphocytes 20% higher than those with negative expression (<i>p</i> = 0.008) with the area under the receiver operating characteristic curve (AUC) being 0.64 (<i>p</i> = 0.002). Among patients with negative NAT, positive PD-L1 expression was associated with peripheral CD8⁺/CD28⁺ T lymphocytes that increased by 54% (<i>p</i> = 0.003), and the AUC being 0.68 (<i>p</i> = 0.003). In patients receiving NAT, positive PD-L1 expression was associated with peripheral TNF-α (<i>p</i> = 0.010), which increased from 0.45pg/mL to 0.64pg/mL in the PD-L1 positive group, and the AUC was 0.79 (<i>p</i> = 0.012). Among patients without NAT experience, a 1% increase in peripheral CD8⁺/CD28⁺ T lymphocytes was associated with a 21% higher probability of positive PD-L1 expression (OR = 1.21, 95% CI: 1.06-1.37) and among patients with NAT, the OR of peripheral TNF-α (>0.5pg/mL) increased to 24.5 for positive TME PD-L1 expression (<i>p</i> = 0.008).</p><p><strong>Conclusion: </strong>Peripheral CD8⁺/CD28⁺ T cell percentages and TNF-α levels served as non-invasive biomarkers for TME PD-L1 expression in BC patients with and without NAT, respectively. These biomarkers warranted further validation in clinical implementation to guide precision immunotherapy.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"627-637"},"PeriodicalIF":3.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288228/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706283","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}