Breast Cancer : Targets and Therapy最新文献

{"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}

{"title":"Suppressing M2 Macrophage Polarization by Glycine Combined with β-Elemene via the IL-6/JAK2/STAT3 Signaling Pathway to Inhibit Triple-Negative Breast Cancer Progression.","authors":"Huan Li, Yu Cheng, Yanyun Meng, Liang Nan, Sicheng Huang, Xiangli Ling, Xiangping Lin, Su Xie","doi":"10.2147/BCTT.S626034","DOIUrl":"10.2147/BCTT.S626034","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is an aggressive subtype with poor prognosis, closely associated with an imbalanced tumor immune microenvironment. Tumor-associated macrophages (TAMs) play a crucial role in tumor progression.</p><p><strong>Purpose: </strong>This study aimed to investigate whether glycine combined with β-elemene inhibits TNBC progression by suppressing M2 macrophage polarization through the IL-6/JAK2/STAT3 pathway.</p><p><strong>Methods: </strong>UPLC-Q-Exactive HRMS was used to identify glycine and β-elemene. In vitro, 4T1 cell viability was determined by CCK-8 assay. RAW264.7 cells were polarized to M2 macrophages and co-cultured with 4T1 cells. Colony formation, wound healing, and Transwell assays were performed. Western blot and immunohistochemistry were used to detect protein expression. In vitro experiments were performed with at least three independent biological replicates. In vivo, 4T1 xenograft mouse models were established (n=10 per group) to evaluate anti-tumor efficacy.</p><p><strong>Results: </strong>Glycine combined with β-elemene significantly suppressed proliferation, colony formation, and migration of 4T1 cells. Mechanistically, the combination inhibited M2 macrophage polarization by downregulating IL-6, p-JAK2, and p-STAT3. In vivo, the combination with paclitaxel showed the strongest anti-tumor effect, with reduced tumor volume and weight, decreased Ki-67 expression, and suppressed M2 polarization.</p><p><strong>Conclusion: </strong>Glycine combined with β-elemene inhibits M2 macrophage polarization by suppressing the IL-6/JAK2/STAT3 pathway, thereby exerting anti-TNBC effects. Its combination with paclitaxel demonstrates synergistic anti-tumor efficacy.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"626034"},"PeriodicalIF":3.6,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148590346","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":"Expression Profiling of SWI/SNF Complex Subunits in Triple-Negative Breast Cancer Using Tissue Microarray and Immunohistochemistry.","authors":"Shang Wang, Chen Gao, Qi Wang, Jing Xu","doi":"10.2147/BCTT.S606605","DOIUrl":"10.2147/BCTT.S606605","url":null,"abstract":"<p><strong>Introduction: </strong>The SWI/SNF (SWItch/Sucrose Non - Fermentable) complex is a multi - subunit, ATPase - dependent chromatin - remodeling complex involved in regulating key cellular processes. Tumors with SWI/SNF loss tend to be poorly differentiated and aggressive. Triple - negative breast cancer (TNBC) typically has a high histological grade and a poor prognosis. Given the limited reports on the SWI/SNF complex in breast cancer, we focused on its role in TNBC.</p><p><strong>Methods: </strong>Using tissue microarray and immunohistochemistry (IHC), we evaluated the expression of four important subunits of the SWI/SNF complex (SMARCB1, SMARCA2, ARID1A, and SMARCA4) in 104 TNBC tissues, which included 96 cases of conventional TNBC and 8 cases of low - grade TNBC. Additionally, we evaluated the endogenous expression of the four subunits in five breast cancer cell lines by real - time quantitative PCR (RT - qPCR). These cell lines consisted of two TNBC cell lines (MDA - MB - 231, MDA - MB - 468) and three non - TNBC cell lines (MCF - 7, T47D, and MDA - MB - 453).</p><p><strong>Results: </strong>The IHC results indicated that the deletion rate of SMARCA2 was the highest in TNBC compared with other subunits (91/104, 87.5%) (p < 0.0001), and SMARCA4 had the highest retention rate (98/104, 94.2%). Whether low - grade TNBC was excluded or not, there was no significant difference between the deletion rate and various clinicopathological parameters. Consistently, we found that SMARCA2 exhibited the lowest expression level across all five cell lines (p < 0.01). SMARCA4 showed the highest expression in all cell lines except MDA - MB - 453, in which ARID1A expression was the highest.</p><p><strong>Conclusion: </strong>These results indicate that TNBC is characterized by a high proportion of SMARCA2 deletion and positive expression of SMARCA4, which are significant molecular features. The roles and potential mechanisms of these two factors in TNBC require further investigation.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"606605"},"PeriodicalIF":3.6,"publicationDate":"2026-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13390667/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560832","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":"Prognostic Significance of Pretreatment Mean Platelet Volume in Patients with Recurrent or De Novo Metastatic Breast Cancer: A Single-Center Retrospective Study.","authors":"Zeynep Sıla Gökdere, Damla Günenç, Serdar Sezer, Aslı Geçgel, Filiz Çay Şenler","doi":"10.2147/BCTT.S629176","DOIUrl":"10.2147/BCTT.S629176","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is the most prevalent malignancy among womificant advances in systemic therapies, metastatic breast cancer remains largely incurable, highlighting the need for reliable prognostic biomarkers. Mean platelet volume (MPV), a routinely measured hematological parameter reflecting platelet size, has been linked to platelet activation, systemic inflammation, and tumor progression. However, the prognostic significance of MPV in recurrent or de novo metastatic breast cancer is unclear. This study evaluated the association between pretreatment MPV and overall survival in this patient population.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on 200 women with recurrent or de novo metastatic breast cancer. Clinical, pathological, and hematological data were collected from medical records. Pretreatment MPV was measured prior to initiation of systemic therapy. MPV was assessed using both the institutional laboratory upper reference limit of 10.5 fL and an exploratory receiver operating characteristic-derived cutoff of 9.55 fL. Overall survival was defined as the interval from diagnosis of recurrent or de novo metastatic disease to death from any cause or last follow-up. Survival outcomes were compared according to MPV status.</p><p><strong>Results: </strong>Pretreatment MPV was not significantly associated with overall survival in patients with recurrent or de novo metastatic breast cancer. Using the institutional cutoff of 10.5 fL, median overall survival was 48 months for patients with MPV <10.5 fL (95% CI: 38.161-57.839) and 108 months for those with MPV ≥10.5 fL (95% CI: 26.214-189.800), with no statistically significant difference between groups (p = 0.693). No significant differences were observed between MPV groups regarding age, menopausal status, tumor biomarkers, metastatic characteristics, or recurrence timing. In multivariable analysis, central nervous system metastasis was independently associated with increased mortality (HR 2.22, 95% CI: 1.224-4.027; p = 0.009), whereas MPV status was not independently associated with overall survival (HR 0.81, 95% CI: 0.379-1.750; p = 0.601).</p><p><strong>Conclusion: </strong>Pretreatment MPV was not identified as an independent prognostic factor for overall survival in patients with recurrent or de novo metastatic breast cancer. Although MPV is an easily accessible hematological parameter, these findings indicate that MPV alone is unlikely to serve as a reliable prognostic biomarker in this clinical context. Further studies with larger cohorts, standardized MPV measurement methods, and adjustment for potential confounding factors are warranted.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"629176"},"PeriodicalIF":3.6,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381613/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599210","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":"Lipid Metabolic Reprogramming in Breast Cancer: Mechanisms and Emerging Therapeutic Strategies.","authors":"Xuliren Wang, Yuanyuan Zhao, Siqi Peng, Xuelong Wang, Qingzhong Wang, Shuang Hao","doi":"10.2147/BCTT.S591634","DOIUrl":"10.2147/BCTT.S591634","url":null,"abstract":"<p><p>Breast cancer remains the most commonly diagnosed malignancy among women worldwide, with a steadily increasing incidence. Lipid metabolic reprogramming is increasingly recognized as both a hallmark and a fundamental driver of breast cancer progression. Breast cancer cells exhibit enhanced lipid uptake, de novo fatty acid synthesis, fatty acid oxidation, and lipid storage, which collectively support membrane biosynthesis, energy production, and oncogenic signaling. In addition to cancer cell-intrinsic effects, lipid metabolic alterations reshape the tumor microenvironment by modulating immune responses, stromal activation, and angiogenesis. Key metabolic enzymes, including FASN, ACC, ACLY, SCD, and FABP4, play central roles in these processes and represent promising therapeutic targets. Emerging evidence from preclinical and clinical studies highlights the therapeutic potential of targeting lipid metabolism, particularly in aggressive subtypes such as triple-negative breast cancer. Despite these advances, challenges such as therapeutic resistance, metabolic compensation, and lack of predictive biomarkers remain major barriers to clinical translation. Overall, targeting lipid metabolic vulnerabilities offers a promising strategy for precision therapy in breast cancer.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"591634"},"PeriodicalIF":3.6,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599176","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":"Application of Shear Wave Elastography Combined with Tumor Markers in the Differential Diagnosis of Benign and Malignant Breast Masses.","authors":"Jing Liu, Yuke Zhang, Qiang Zhou","doi":"10.2147/BCTT.S614367","DOIUrl":"10.2147/BCTT.S614367","url":null,"abstract":"<p><strong>Purpose: </strong>To explore the value of combined quantitative shear wave elastography (SWE) parameters and breast cancer molecular markers for the differential diagnosis of benign and malignant breast masses.</p><p><strong>Methods: </strong>This study retrospectively analyzed the clinical data of 225 patients who underwent conventional ultrasound, SWE examinations, immunohistochemical analysis, and measurement of serum tumor markers CA15-3 and CA125. Based on the pathological diagnoses, the patients were categorized into malignant (n=107) and benign (n=118) mass groups.</p><p><strong>Results: </strong>The malignant mass group exhibited significantly higher values of quantitative SWE parameters, including maximum elasticity (E max), Shell1 E max, Shell2 E max, and Shell3 E max, than the benign mass group (<i>P</i><0.05). Hemodynamic indicators, including the maximum blood flow velocity, resistance index, and pulsatility index, were also markedly elevated in the malignant mass group (<i>P</i><0.05). Regarding the SWE imaging classification, the malignant mass group primarily corresponded to Types IV and V, whereas the benign mass group was mainly classified as Types I and II (<i>P</i><0.001). Serum tumor markers CA15-3 and CA125 were significantly elevated in the malignant mass group. The combined detection of quantitative SWE parameters, CA15-3, and CA125 demonstrated higher AUC values than single detection, suggesting that the integration of SWE parameters with CA15-3 and CA125 significantly enhances diagnostic efficacy in differentiating benign from malignant breast masses (<i>P</i><0.01).</p><p><strong>Conclusion: </strong>The combined detection of quantitative SWE parameters and breast cancer molecular markers significantly enhances the accuracy of differentiating benign from malignant breast masses.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"614367"},"PeriodicalIF":3.6,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13378508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148577100","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 Expression and Axillary Metastasis in Treatment-Naïve Early Breast Cancer.","authors":"Ferit Aydin, Cemil Yuksel, Cuneyt Akyuz, Huseyin Pulat, Emre Tunc, Mehmet Furkan Sağdıç, Bulent Aksel, Lutfi Dogan","doi":"10.2147/BCTT.S618927","DOIUrl":"10.2147/BCTT.S618927","url":null,"abstract":"<p><strong>Purpose: </strong>The clinical significance of human epidermal growth factor receptor 2 (HER2)-low breast cancer remains controversial, particularly in early-stage, treatment-naïve patients. Because neoadjuvant therapy may alter tumor biology and nodal status, we specifically evaluated patients who underwent upfront surgery without prior systemic treatment. We also investigated whether the recently recognized HER2-ultralow subgroup exhibited differences in axillary metastatic involvement.</p><p><strong>Patients and methods: </strong>In this multicenter observational study, we retrospectively analyzed 407 patients with hormone receptor-positive early-stage breast cancer who underwent upfront surgery between 2017 and 2023 without neoadjuvant therapy. Patients were categorized as HER2-ultralow (immuno-histochemistry [IHC] 0), HER2-low (IHC 1+ or 2+ with fluorescence in situ hybridization [FISH] negative), or HER2-positive (IHC 3+ or 2+ with FISH positive). Groups were compared for sentinel lymph node (SLN) positivity. Multivariable logistic regression and receiver operating characteristic (ROC) analyses were used to identify predictors of axillary metastasis.</p><p><strong>Results: </strong>SLN positivity rates were similar across the HER2-ultralow (29.0%, n = 288), HER2-low (30.6%, n = 80), and HER2-positive groups (31.3%, n = 39) (p = 0.941). HER2 expression was not an independent predictor of SLN positivity. Lymphovascular invasion (LVI) was the strongest determinant (odds ratio = 5.42; 95% confidence interval: 3.13-9.39; p < 0.001). Larger tumor size and higher proliferative activity were independently associated with increased axillary involvement. ROC analysis showed higher discrimination for LVI (AUC = 0.68) than Ki-67 (AUC = 0.53) and tumor size (AUC = 0.61). Exploratory survival analyses demonstrated no statistically significant differences among groups; however, these findings should be interpreted cautiously because of the limited follow-up duration and low number of events.</p><p><strong>Conclusion: </strong>In hormone receptor-positive early-stage breast cancer treated with upfront surgery, HER2 expression was not independently associated with axillary metastasis risk in this treatment-naïve cohort. Classical pathological factors, particularly lymphovascular invasion, larger tumor size, and higher proliferative activity, remained the principal determinants of axillary involvement.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"618927"},"PeriodicalIF":3.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361310/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435290","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":"AIM2 Lactylation Regulates Radiotherapy Sensitivity in Triple-Negative Breast Cancer.","authors":"Jianli Chen, Ziming Zhao, Yangyang Xing, Xiaorui Li, Di Liu, Lijia Liu, Mingyu Yang, Hua Zhou, Jue Wang, Qibiao Wu","doi":"10.2147/BCTT.S613159","DOIUrl":"10.2147/BCTT.S613159","url":null,"abstract":"<p><strong>Background: </strong>Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with limited targeted treatment options. Radiotherapy remains an important therapeutic approach for TNBC, but radioresistance markedly limits its efficacy. Absent in melanoma 2 (AIM2) has been increasingly implicated in tumor biology and innate immune signaling; however, its role in TNBC radioresistance and its regulation by the lactate-rich tumor microenvironment remain unclear.</p><p><strong>Methods: </strong>Radiation-resistant TNBC cell models were established from BT-549 and MDA-MB-231 cells by repeated fractional irradiation. AIM2 knockdown and IRF3 overexpression were achieved by lentiviral transduction. Cell proliferation, colony formation, apoptosis, protein expression, AIM2 lactylation, subcellular localization, and AIM2-IRF3 interaction were evaluated using CCK-8 assay, colony formation assay, flow cytometry, RT-qPCR, Western blotting, co-immunoprecipitation, and immunofluorescence. Bioinformatics analyses were performed to assess the potential prognostic relevance of AIM2. In vitro experiments were performed with at least three independent biological replicates.</p><p><strong>Results: </strong>Radiation treatment increased AIM2 expression in TNBC cells. AIM2 knockdown reduced colony formation and promoted apoptosis in radioresistant TNBC cells. High-lactate conditions decreased AIM2 expression, increased AIM2 lactylation, and promoted AIM2 nuclear translocation. IRF3 overexpression partially reversed the effects of AIM2 knockdown on colony formation and apoptosis, whereas lactate treatment weakened the interaction between AIM2 and IRF3. Bioinformatics analyses indicated that elevated AIM2 expression was associated with poorer prognosis.</p><p><strong>Conclusion: </strong>These findings suggest that AIM2 may be involved in the regulation of TNBC radioresistance, potentially through its interaction with IRF3. High-lactate conditions may affect this regulatory axis by enhancing AIM2 lactylation. This study provides preliminary evidence for a potential mechanism linking lactate-mediated post-translational modification with radiosensitivity regulation in TNBC; however, further mechanistic, in vivo, and clinical validation is required.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"18 ","pages":"613159"},"PeriodicalIF":3.6,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13361780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148435143","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}