Breast Cancer : Targets and Therapy最新文献

Purpose: This study aimed to evaluate differences in tumor characteristics, molecular subtypes, and surgical approaches between elderly (≥70 years) and younger (<70 years) breast cancer patients.

Patients and methods: This retrospective, single-center study analyzed 120 breast cancer patients (99 younger, 21 elderly) treated surgically between 2020 and 2025 at Istanbul Aydın University, Turkey. Tumor characteristics and surgical management related data were analyzed to compare two age groups. Statistical analyses included t-tests, chi-square tests, and Fisher's exact tests.

Results: Elderly patients presented with significantly larger tumors (3.91±0.56 vs 2.81±0.35 cm, p<0.05), higher T4 disease prevalence (19.05% vs 3.37%, p<0.05), and greater metastatic burden (7.90±6.06 vs 3.54±4.49 metastases, p<0.05). SLNB was performed significantly more frequently in younger patients (90.9%) compared to elderly patients (71.4%, p < 0.05). Elderly patients underwent axillary dissection in 57.1% of cases compared to 33.3% in younger patients. Advanced tumors (T3+T4) were more prevalent in elderly patients with Luminal B HER2-positive (33.3% vs 0%, p<0.0001) and Luminal B HER2-negative (37.5% vs 8.3%, p<0.05) subtypes. Surgical management differed significantly between groups: mastectomy was performed more frequently in elderly patients (57.14% vs 31.31%, p<0.05), whereas breast-conserving surgery was less common (42.9% vs 67.7%, p<0.05).

Conclusion: These findings demonstrate important differences in disease presentation and surgical management between age groups in Turkey, where breast cancer screening ends at age 69. The absence of screening detection in elderly patients, combined with their advanced disease presentation, highlights the need for further investigation with larger, multicenter cohorts to evaluate optimal screening strategies for women beyond age 69.

Purpose: To investigate the effect of modified Shuyu pill on the timing of TNBC metastasis, MDSCs recruitment in tumor tissues and distant target organs, and the impact on the JAK2/STAT3 signaling pathway.

Methods: The fingerprint profile of the modified Shuyu pill was obtained using UPLC-Q-Exactive HRMS technology. A TNBC-bearing mouse model was established, and the mice were treated with modified Shuyu pill granules (low, medium, and high doses), paclitaxel (PTX), or saline for 25 days. Tumor growth was monitored during treatment, and small animal in vivo imaging was performed on days 1, 7, 14, 21, and 25. On day 21 of treatment, flow cytometry was used to assess the proportion of G-MDSCs and M-MDSCs in peripheral blood, spleen, lungs, and tumor tissues. Immunofluorescence was used to detect the number and distribution of MDSCs in the lungs and liver. Western blotting and RT-qPCR were used to detect the expression of proteins and genes related to the JAK2/STAT3 signaling pathway in tumor tissues.

Results: The modified Shuyu pill inhibited tumor growth and distant metastasis in 4T1 tumor-bearing mice, and its anti-tumor effect was enhanced when combined with paclitaxel. More importantly, modified Shuyu pill suppressed the recruitment of MDSCs in the peripheral blood, spleen, lungs, liver, and tumors of tumor-bearing mice, thereby inhibiting the formation of the pre-metastatic niche. Mechanistically, modified Shuyu pill inhibited the expression of proteins in the JAK2/STAT3 signaling pathway, including IL-6, JAK2, p-JAK2, STAT3, p-STAT3 (Tyr705), p-STAT3 (Ser727), S100A8, S100A9, NF-κB, MMP2, and MMP9, and this effect was more pronounced when combined with paclitaxel.

Conclusion: The modified Shuyu Pill can downregulate the JAK2/STAT3 signaling pathway, reduce the number of MDSCs in the tumor microenvironment and distant lung tissues of tumor-bearing mice, inhibit the formation of pre-metastatic niches, and ultimately suppress tumor growth and metastasis.

Background and purpose: Breast cancer presents a substantial clinical challenge because of its complex aetiology and diverse phenotypic presentations. ST6Gal1 expression and epithelial-to-mesenchymal transition (EMT) frequently lead to metastasis, drug resistance and poor prognosis in many cancers. Nevertheless, the molecular details surrounding ST6GAL1 in the carcinogenesis of breast cancer, especially in the EMT of breast cancer, remain unclear. The objective of this study was to clarify the possible role and mechanism of ST6GAL1 in breast cancer.

Methods: PCR, WB, and IHC were employed to analyze the expression of ST6GAL1, epithelial-mesenchymal transition (EMT) markers, and components of the HIF-HK2 signaling pathway in MCF-10A, MDA-MB-231, and MCF-7 cells. Wound-healing, cell adhesion, drug resistance and extracellular matrix invasion assays were used to analyse the effects of ST6GAL1 on the biological process of breast cancer cells. The HIF-HK2 signalling pathway was also analysed.

Results: ST6GAL1 expression is increased in breast cancer. Altered expression of ST6GAL1 affects the biological function of breast cancer cells both in vitro and in vivo. ST6GAL1 knockdown inhibited EMT in breast cancer cells. ST6GAL1 Mediates the Activity of the HIF-HK2 Signalling Pathway in Breast Carcinoma Cells.

Conclusion: In our study, in vitro and in vivo models revealed that ST6GAL1 promotes malignant phenotypes in breast cancer cells and regulates the EMT process through activation of the HIF-HK2 signalling pathway.

Background: Inflammatory bowel disease (IBD) and breast cancer represent significant global health burdens. Although epidemiological studies have suggested a potential link between them, the causal relationship and underlying molecular mechanisms remain unclear. This study employed Mendelian randomization (MR) and multi-omics approaches to investigate the causal association between IBD and breast cancer and to explore shared genetic biomarkers and pathological pathways.

Methods: A two-sample MR analysis was performed using genome-wide association study (GWAS) data. Shared genes were identified and validated using the GEO and TCGA databases. THBS3 expression was further verified in human breast cancer tissues via immunohistochemistry and RT-PCR. Immune infiltration analysis, drug sensitivity assessment, molecular docking, ceRNA network construction, and pathway enrichment analyses (GSEA and GSVA) were conducted to explore the functional role of THBS3.

Results: MR analysis indicated that IBD significantly increases the risk of breast cancer. THBS3 was identified as a commonly overexpressed gene in both diseases and was associated with poor prognosis. THBS3-high breast cancer patients exhibited resistance to Dinaciclib, Daporinad, and Rapamycin. Molecular docking and dynamics simulations confirmed a strong binding affinity between THBS3 and Rapamycin. A ceRNA network linked THBS3 to miR-423-5p and chemotherapy resistance-related lncRNAs. Pathway analyses revealed THBS3 involvement in extracellular matrix receptor interaction and proteasome pathways.

Conclusion: This study provides genetic evidence supporting IBD as a risk factor for breast cancer and highlights THBS3 as a key shared biomarker. THBS3 may promote breast cancer progression through immune regulation, ECM remodeling, and drug resistance mechanisms, suggesting its potential as a therapeutic target. These findings support enhanced breast cancer screening in IBD patients.

Introduction: Aberrant acquisition of lipoprotein cholesterol remains a hallmark feature of breast cancer biology. Low- and high-density lipoprotein receptors (LDLR and scavenger receptor class B type 1 (SR-B1)) are often upregulated to facilitate the tumor cells' high demand for cholesterol. To date, few attempts have been made to therapeutically exploit the high activity of lipoprotein receptors in breast cancer cells.

Methods: In the present study, we examined the utility of engineered low-density lipoprotein nanoparticles to deliver the natural anticancer omega-3 fatty acid docosahexaenoic acid (LDL-DHA) across a panel of breast cancer cells.

Results: Our data showed that LDL-DHA nanoparticles were avidly taken up (K_D 28 µg/mL to 1.9 µg/mL) and cytotoxic to all breast cancer subtypes (LD₅₀ 52.2 µM to 4.7µM), with triple negative breast cancer cells showing some of the highest uptake and sensitivity to LDL-DHA. Follow-up receptor knockout studies in MDA-MB-231 cells revealed that LDL nanoparticle uptake is mediated by both LDLR and SR-B1. These receptors were shown to operate concurrently as well as in a compensatory manner to ensure ample uptake of LDL is maintained. Double knockout of LDLR and SR-B1 significantly impeded LDL nanoparticle uptake (<50%) and protected against LDL-DHA cytotoxicity (viability >70%).

Conclusion: In summary, our studies have shown that malignant cell dependence upon cholesterol acquisition can be exploited for lipoprotein-based drug delivery to breast cancer cells. Furthermore, the capacity of LDL nanoparticles to target both LDLR and SR-B1 ensures this as an efficient drug delivery platform against breast cancer cells.

Objective: At present, the potential functions of most circRNAs in breast cancer (BC) have not been fully elucidated. The investigatory research planned to study biological function of circDENND4C in BC and reveal its downstream molecular mechanism.

Methods: A total of fifty pairs of BC tissue and their corresponding normal tissue were obtained. circDENND4C/miR-26a-5p/Human 71 kDa heat shock cognate protein (HSPA8) were assessed through RT-qPCR or Western blot. After transfecting the relevant plasmids, MKN-45 cell proliferation, cell cycle, invasion, and migration were assessed through MTT and colony formation assays, flow cytometry, and Transwell tests. Bioinformatics analysis, RIP and dual luciferase reporting experiments verified the interaction between circDENND4C, miR-26a-5p, and HSPA8.

Results: Increased circDENND4C was found in BC and was related to a poor prognosis in BC patients. HSPA8 was upregulated and miR-26a-5p was downregulated in BC. Functionally, silencing circDENND4C prevented cells from proliferation, invasion, and migration, and induced cell cycle arrest at G0/G1 phase. circDENND4C overexpression had the opposite effect. The effects of circDENND4C overexpression or knockdown in BC cells were counteracted by overexpressing miR-26a-5p or HSPA8, respectively. circDENND4C mediated HSPA8 expression by competitively adsorbing miR-26a-5p.

Conclusion: circDENND4C absorbs miR-26a-5p to target HSPA8, thereby promoting BC progression, which provides a new insight into the mechanism of BC.

Aim: To develop and validate a radiomics-based nomogram using multimodal magnetic resonance imaging (MRI) features to predict HER-2 expression status in breast cancer.

Methods: A total of 320 breast cancer patients were retrospectively selected for this study, with 80 in the HER-2 positive group and 240 in the HER-2 negative group. Pre-treatment multimodal MRI scans, including dynamic contrast-enhanced MRI (DCE-MRI), diffusion-weighted imaging (DWI), and T2-weighted imaging, were used to extract radiomic features. Multivariate logistic regression was performed to identify independent predictors for HER-2 positivity. A radiomics-based nomogram was constructed and validated using both training and validation sets. The nomogram's performance was assessed using receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA).

Results: Multivariate analysis identified several independent predictors of HER-2 positivity, including type, edge, local skin thickening or depression, and axillary lymph node enlargement. The radiomics-based nomogram demonstrated excellent predictive accuracy with an area under the ROC curve (AUC) of 0.866 in the training set and 0.876 in the validation set. Calibration plots confirmed the model's good consistency, and DCA indicated that the nomogram provides significant clinical benefit across a range of threshold probabilities. In addition, the HER-2 positive group showed significantly higher tumor marker expression and immune cell infiltration, including elevated CD8+ T-cells, M1 macrophages, Tregs, and TAM (p<0.001).

Conclusion: The radiomics-based nomogram developed in this study offers a promising non-invasive tool for predicting HER-2 expression status in breast cancer. By integrating clinical data and advanced MRI features, this model provides accurate predictions, improving personalized treatment strategies. Further validation in larger, multicenter studies is necessary to confirm its generalizability and clinical applicability.

Background: CTBP1, an NADH-dependent transcriptional co-repressor subject to succinylation, may orchestrate both systemic and cell-type-specific effects on tumor development.

Methods: This integrative study represents a novel approach, combining genetic regulation, single-cell expression quantitative trait loci (eQTLs), and imaging radiomics to investigate CTBP1 in breast cancer. We integrated tissue-relevant eQTLs with breast cancer GWAS to evaluate genetically proxied associations for CTBP1. We further explored cell-type-dependent effects using single-cell eQTL resources and examined expression, survival, and imaging correlations as hypothesis-generating evidence.

Results: Tissue-focused analyses suggested an inverse association between CTBP1 expression and breast cancer risk, with consistent directions observed in expression and survival datasets. Single-cell explorations indicated potential cell-type-specific regulation.Imaging correlations with MRI-derived features were modest and exploratory.

Conclusion: Our results prioritise CTBP1 as a context-dependent, tissue- and cell-type-specific candidate in breast cancer. The observational and exploratory components warrant validation in larger cohorts and functional assays. To our knowledge, this is the first integrative study combining GWAS, single-cell eQTL and MRI radiomics to prioritize CTBP1 in breast cancer.

The integration of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with radiomics has emerged as a transformative approach for non-invasive prediction of breast cancer molecular subtypes. This review systematically evaluates methodological innovations, clinical validation milestones, and translational applications: (1) Methodological Advancements: Standardized DCE-MRI protocols combined with multidimensional radiomic features (morphological, textural, and wavelet-transformed parameters) significantly improved discriminative performance for ER, HER2, and triple-negative subtypes. (2) Deep Learning Integration: Multitask predictive models achieved early treatment response assessment and recurrence risk stratification through spatiotemporal heterogeneity analysis. (3) Clinical Validation: Prospective multicenter trials demonstrated that radiomic models showed strong concordance with 21-gene assays and could potentially replace 38% of repeat biopsies. Despite these advancements, challenges persist in data heterogeneity and mechanistic interpretation of radiomic biomarkers. Emerging strategies integrating radiogenomic analyses and organoid validation platforms are establishing new paradigms for precision imaging-guided therapy.

Background: Cardiotoxicity is the most concerning side effect of trastuzumab in HER2-positive metastatic breast cancer. However, data on the delayed cardiac safety of long-term trastuzumab are rare.

Patients and methods: A retrospective review of patients with HER2-positive breast cancer receiving trastuzumab for more than 24 months in a metastatic setting was conducted. Patients with medical records of regular assessment of the left ventricular ejection fraction (LVEF) and serum brain natriuretic peptide (BNP) level were included. The incidence of cardiac events and possible predictive factors were analyzed.

Results: A total of 75 patients were eligible for the current cardiac safety analyses. The median trastuzumab exposure was 50 (range: 29-114) cycles. By the cut-off time, the median follow-up time for cardiotoxicity was 34.0 (range: 26.0-41.9) months. The median timing of occurrence of a decrease in LVEF was 8.3 months after follow-up, mostly occurring within the third year from the initiation of trastuzumab. The cumulative incidence of LVEF decline was 10.7% (n=8) after 24-month trastuzumab. Patients with a history of anthracycline administration had a higher incidence of LVEF reduction (13.0% vs 3.6%, p=0.006). Five patients recovered soon after the cessation of trastuzumab. One patient died from congestive heart failure. BNP elevations were noted in 42.7% of patients, but elevated BNP levels could not identify patients with cardiotoxicity.

Conclusion: Of the patients who had received long-term trastuzumab for more than 24 months, delayed cardiotoxicity was observed in only a small subset, and was reversible in most of them. Elevation of serum BNP could not predict cardiotoxicity. Less frequent LVEF monitoring could be considered during long-term use of trastuzumab.