Breast Cancer Research最新文献

{"title":"CPT1A/HIF-1α positive feedback loop induced fatty acid oxidation metabolic pathway contributes to the L-ascorbic acid-driven angiogenesis in breast cancer.","authors":"Xiao Ma, Baojian Zhang, Xuezhe Yin, ShiPeng Yang, Zhenhua Lin, Yang Yang, Xianchun Zhou","doi":"10.1186/s13058-025-02039-0","DOIUrl":"10.1186/s13058-025-02039-0","url":null,"abstract":"<p><strong>Background: </strong>In tumors rich in adipose tissue, angiogenesis is a critical factor in promoting cancer cell metastasis. However, the connection between angiogenesis and the mechanisms driving adipose metabolic remodeling in breast cancer (BC) remains insufficiently understood. This research seeks to explore whether and how CPT1A, a crucial rate-limiting enzyme in fatty acid oxidation (FAO), supports angiogenesis through metabolic pathways in BC.</p><p><strong>Methods: </strong>First, cell functional assays and animal models were employed to elucidate the pro-carcinogenic effects of CPT1A on BC and its role in metabolic alterations. Following this, the reciprocal regulatory relationship between CPT1A and HIF-1α was elucidated using transcriptomic studies, ubiquitination analysis, and dual-luciferase assays. Matrigel tube formation assays, vasculogenic mimicry assays, and chick chorioallantoic membrane (CAM) assays were utilized to evaluate the effect of CPT1A on the pro-angiogenic properties of BC. Subsequently, untargeted metabolomics was employed to identify specific metabolic changes in supernatants with and without CPT1A expression and verified by functional recovery experiments. Finally, the prognostic significance of CPT1A and the vascular marker VEGF in BC tissues was evaluated using tissue microarrays and public databases.</p><p><strong>Results: </strong>CPT1A overexpression significantly enhanced cell proliferation, motility, and angiogenesis via activating the FAO metabolic pathway, as demonstrated by both in vivo and in vitro experiments. Mechanistically, CPT1A regulates the ubiquitination level of hypoxia-inducible factor-1α (HIF-1α), which directly binds to the CPT1A promoter. Mutations at the 63-74 and 434-445 regions significantly reduced CPT1A promoter activity, indicating that these sites are critical for its transcriptional regulation. Ultimately, this interaction creates a reinforcing feedback loop between CPT1A and HIF-1α. Subsequently, this feedback loop alters changes in extracellular L-ascorbic acid (LAA) levels. Interestingly, LAA affects ROS homeostasis through the Nrf2/NQO1 pathway, specifically influencing angiogenesis in BC and HUVECs, while having no significant effect on their proliferation or EMT process. Moreover, increased expression levels of CPT1A and vascular endothelial growth factor (VEGF) were significantly associated with lymph node metastasis and adverse outcomes in BC patients.</p><p><strong>Conclusion: </strong>The CPT1A/HIF-1α positive feedback loop critically regulates angiogenesis through activation of the Nrf2/NQO1 pathway, modulated by LAA. These findings highlight CPT1A and VEGF as promising therapeutic targets and prognostic biomarkers for angiogenesis in BC.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"74"},"PeriodicalIF":7.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067761/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating immune cells exhibit distinct traits linked to metastatic burden in breast cancer.","authors":"S Mangiola, R Brown, C Zhan, J Berthelet, S Guleria, C Liyanage, S Ostrouska, J Wilcox, M Merdas, P Fuge-Larsen, C Bell, J Schröder, L A Mielke, J M Mariadason, S Chang-Hao Tsao, Y Chen, V K Yadav, S Vodala, R L Anderson, D Merino, A Behren, B Yeo, A T Papenfuss, B Pal","doi":"10.1186/s13058-025-01982-2","DOIUrl":"https://doi.org/10.1186/s13058-025-01982-2","url":null,"abstract":"<p><strong>Background: </strong>Circulating immune cells play a crucial role in the anti-tumour immune response, yet the systemic immune system in metastatic breast cancers is not fully characterised. Investigating the cellular and molecular changes in peripheral blood mononuclear cells (PBMCs) from breast cancer patients could elucidate the role of circulating immune cells in metastasis and aid in identifying biomarkers for disease burden and progression.</p><p><strong>Methods: </strong>In this study, we characterised the systemic immune landscape associated with varying levels of metastatic burden by analysing the single-cell transcriptomes of PBMCs from breast cancer patients and healthy controls. Our research focused on identifying changes in immune cell composition, transcriptional programs, and immune-cell communication networks linked to metastatic burden. Additionally, we compared these PBMC features onto a single-cell atlas of primary breast tumours to study corresponding traits in tumour-infiltrating immune cells.</p><p><strong>Results: </strong>In metastatic breast cancer, PBMCs exhibit a significant downregulation of the adaptive immune system and a decreased number and activity of unconventional T cells, such as γδ T cells. Additionally, metastatic burden is associated with impaired cell communication pathways involved in immunomodulatory functions. We also identified a gene signature derived from myeloid cells shared between tumour immune infiltrates and circulating immune cells in breast cancer patients.</p><p><strong>Conclusions: </strong>Our study provides a comprehensive single-cell molecular profile of the peripheral immune system in breast cancer, offering a valuable resource for understanding metastatic disease in terms of tumour burden. By identifying immune traits linked to metastasis, we have unveiled potential new biomarkers of metastatic disease.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"73"},"PeriodicalIF":7.4,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12063295/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143989559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"8MW0511, a novel, long-acting granulocyte-colony stimulating factor fusion protein for the prevention of chemotherapy-induced neutropenia: final results from the phase III clinical trial.","authors":"Biyun Wang, Xiuchun Chen, Hongtao Li, Jing Sun, Xinjian Jia, Tao Sun, Yumin Yao, Jingfen Wang, Jincheng Li, Xujuan Wang, Xiaojia Wang, Cuizhi Geng, Yu Ren, Liuzhong Yang, Jun Jia, Yiding Chen, Zhihua Li, Yunhui Huang, Baojiang Li, Guosheng Ren, Jian Chen, Shiyou Yu, Jiazhuan Mei, Zhidong Pei, Caixia Liu, Xuchen Cao, Chao Deng, Mingde Huang, Yueyin Pan, Yi Tu, Zhiye Zhang, Ruizhen Luo, Peipei Wang, Jingming Dong, Honghuan Zhao, Song Lu, Chaolong Zhu, Shaona Cai, Shuhai Wang, Xichun Hu","doi":"10.1186/s13058-025-02010-z","DOIUrl":"https://doi.org/10.1186/s13058-025-02010-z","url":null,"abstract":"<p><strong>Background: </strong>8MW0511 is a novel, long-acting recombinant human granulocyte-colony stimulating factor (G-CSF) produced by the fusion of the N-terminus of highly active modified G-CSF with the C-terminus of human serum albumin (HSA). Current G-CSF treatments require frequent administration and have limitations in efficacy and convenience, highlighting the need for a longer-acting alternative with fewer injections and improved outcomes. Here, we report a phase III study comparing the efficacy and safety of 8MW0511 with those of the approved PEG-rhG-CSF.</p><p><strong>Methods: </strong>Patients with breast cancer were randomized at a 2:1 ratio to receive either 8MW0511 or PEG-rhG-CSF after four cycles of standard chemotherapy with docetaxel and cyclophosphamide, with or without doxorubicin. The primary efficacy endpoint was to evaluate the duration of severe neutropenia (DSN) between 8MW0511 and PEG-rhG-CSF during the first cycle.</p><p><strong>Results: </strong>Eligible patients were enrolled and randomly assigned to receive either 8MW0511 (n = 328) or PEG-rhG-CSF (n = 164). During the first cycle, the average DSN was 0.24 days for the 8MW0511 group and 0.25 days for the PEG-rhG-CSF group. The mean difference in DSN [-0.02 days (95% Confidence interval: -0.12, 0.08)] met the primary study endpoint. During cycles 2-4, the DSN results were consistent with those of cycle 1. The incidence of grade 4 neutropenia was lower in the 8MW0511 group than in the PEG-rhG-CSF group across all chemotherapy cycles. The incidence of febrile neutropenia (FN) across all cycles showed no significant difference between the two groups. Other efficacy endpoints and adverse events were comparable between the two groups.</p><p><strong>Conclusions: </strong>The study findings confirm that 8MW0511 is not inferior to PEG-rhG-CSF in terms of efficacy and shows comparable safety profiles. Additionally, 8MW0511 has the potential to significantly decrease the duration of chemotherapy-induced neutropenia, along with a reduction in the occurrence of FN and severe neutropenia.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"71"},"PeriodicalIF":7.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AXL promotes inflammatory breast cancer progression by regulating immunosuppressive macrophage polarization.","authors":"Lan T H Phi, Yating Cheng, Yohei Funakoshi, Francois Bertucci, Pascal Finetti, Steven J Van Laere, Fang Zou, James P Long, Suguru Ogata, Savitri Krishnamurthy, James M Reuben, Jason M Foulks, Steven L Warner, Jennifer M Rosenbluth, Anil K Sood, Debu Tripathy, Naoto T Ueno, Xiaoping Wang","doi":"10.1186/s13058-025-02015-8","DOIUrl":"https://doi.org/10.1186/s13058-025-02015-8","url":null,"abstract":"<p><strong>Background: </strong>Tumor-associated macrophages (TAMs) are key promoters of inflammatory breast cancer (IBC), the most aggressive form of breast cancer. The receptor tyrosine kinase AXL is highly expressed in various cancer types, including IBC, but its role in TAMs remains unexplored.</p><p><strong>Methods: </strong>We examined the effects of AXL inhibitor TP-0903 on tumor growth and tumor microenvironment (TME) component M2 macrophages (CD206⁺) in IBC and triple-negative breast cancer mouse models using flow cytometry and immunohistochemical staining. Additionally, we knocked out AXL expression in human THP-1 monocytes and evaluated the effect of AXL signaling on immunosuppressive M2 macrophage polarization and IBC cell growth and migration. We then investigated the underlying mechanisms through RNA sequencing analysis. Last, we performed CIBERSORT deconvolution to analyze the association between AXL expression and tumor-infiltrating immune cell types in tumor samples from the Inflammatory Breast Cancer International Consortium.</p><p><strong>Results: </strong>We found that inhibiting the AXL pathway significantly reduced IBC tumor growth and decreased CD206⁺ macrophage populations within tumors. Mechanistically, our in vitro data showed that AXL promoted M2 macrophage polarization and enhanced the secretion of immunosuppressive chemokines, including CCL20, CCL26, and epiregulin, via the transcription factor STAT6 and thereby accelerated IBC cell growth and migration. RNA sequencing analysis further indicated that AXL signaling in immunosuppressive M2 macrophages regulated the expression of molecules and cytokines, contributing to an immunosuppressive TME in IBC. Moreover, high AXL expression was correlated with larger populations of immunosuppressive immune cells but smaller populations of immunoactive immune cells in tissues from patients with IBC.</p><p><strong>Conclusions: </strong>AXL signaling promotes IBC growth by inducing M2 macrophage polarization and driving the secretion of immunosuppressive molecules and cytokines via STAT6 signaling, thereby contributing to an immunosuppressive TME. Collectively, these findings highlight the potential of targeting AXL signaling as a novel therapeutic approach for IBC that warrants further investigation in clinical trials.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"70"},"PeriodicalIF":7.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057249/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144018522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomechanical parameters quantified by MR elastography for predicting response to neoadjuvant chemotherapy and disease-free survival in breast cancer: a prospective longitudinal study.","authors":"Xiaoxia Wang, Yao Huang, Jinfang Shi, Ying Cao, Huifang Chen, Lan Li, Lu Wang, Sun Tang, Xueqin Gong, Haiping Huang, Ting Yin, Jiuquan Zhang","doi":"10.1186/s13058-025-02035-4","DOIUrl":"https://doi.org/10.1186/s13058-025-02035-4","url":null,"abstract":"<p><strong>Background: </strong>Little is known regarding biomechanical properties derived from multifrequency MR elastography temporal changes during neoadjuvant chemotherapy (NAC) and associated with pathologic complete response (pCR) and disease-free survival (DFS) in breast cancer. We aimed to investigate temporal changes in NAC-associated biomechanical parameters and assess biomechanical parameters as a predictor of pCR and DFS in breast cancer.</p><p><strong>Methods: </strong>In this prospective longitudinal study, participants with breast cancer who received NAC were enrolled from February 2021 to May 2023. All participants underwent multifrequency MR-elastography at four timepoints: before NAC (T1) and after 2 (T2), 4 (T3), and 6 (T4) cycles. Tomoelastography postprocessing provided biomechanical maps of shear-wave-speed (c) and loss-angle (φ) as proxies of stiffness and viscosity. The biomechanical parameters were validated by means of correlation with histopathologic measurements. Generalized estimating equations were used to compare temporal changes in biomechanical parameters at four time points. Logistic regression was used for pCR analysis and Cox proportional hazards regression was used for survival analysis. Predictive performance was assessed with area under the receiver operating characteristic curve (AUC) analysis.</p><p><strong>Results: </strong>A total of 235 women (50.6 ± 7.9 years) with 964 scans were enrolled. Biomechanical parameters were supported by positive correlations with pathologic examination-based stroma fraction (c: r =.76, P <.001; φ: r =.49, P =.008) and cellularity (c: r =.58, P =.001; φ: r =.40, P =.035). Progesterone receptor, human epidermal growth factor receptor-2 (HER2), T2-c, and T2-φ were independently associated with pCR (all P <.05). Estrogen receptor, HER2, clinical stage, and change in φ at the early stage of NAC were associated with PFS (all P <.05). The predictive model, which incorporated biomechanical parameters and clinicopathologic characteristics significantly outperformed the clinicopathologic model in predicting pCR (AUC: 0.95, 95% confidence interval [CI]: 0.92, 0.98 vs. 0.79, 95%CI: 0.73, 0.84; P <.001). The predictive model also showed good discrimination ability for DFS (C-index = 0.82, 95%CI: 0.72, 0.90) and stratified prognosis into low-risk and high-risk groups (log-rank, P <.001).</p><p><strong>Conclusions: </strong>During NAC, patients with higher tumor stiffness and viscosity are less likely to achieve DFS and pCR. The biomechanical parameters exhibit excellent biological interpretability and serve as valuable biomarkers for predicting pCR and DFS in patients with breast cancer.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"72"},"PeriodicalIF":7.4,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12057177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144024221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review.","authors":"Samane Heydari, Fatemeh Tajik, Sadegh Safaei, Fereshteh Kamani, Babak Karami, Shima Dorafshan, Zahra Madjd, Roya Ghods","doi":"10.1186/s13058-025-02017-6","DOIUrl":"https://doi.org/10.1186/s13058-025-02017-6","url":null,"abstract":"<p><strong>Background: </strong>The tumor microenvironment (TME), particularly the extracellular matrix (ECM), plays a crucial role in regulating breast cancer progression. Among ECM components, collagen type I-accounting for over 90% of fibrillar collagen in the human body-is the primary structural component of the tumor ECM. It critically modulates tumor cell behavior, influencing migration, invasion, and therapy resistance. The structural organization of collagen type I fibers can significantly impact clinical outcomes.</p><p><strong>Methods: </strong>This systematic review aimed to assess the association between tumor-stromal collagen type I characteristics and clinical outcomes in breast cancer. A comprehensive search strategy identified studies from major databases, which were appraised using quality assessment tools. Data on collagen quantity, morphology, alignment, and organization were extracted and analyzed to explore their relationship with survival, metastasis, therapy resistance, and clinical characteristics of breast cancer.</p><p><strong>Results: </strong>Our analysis revealed that increased collagen density-particularly with an organized/aligned fiber orientation-was strongly associated with poor prognosis. Specifically, increased intratumoral collagen quantity was linked to reduced overall survival (HR = 7.84, p = 0.031). Stage III tumors exhibiting elevated collagen uniformity showed higher metastasis rates (p = 0.004), and HER2⁺ tumors with high collagen content correlated with resistance to HER2-targeted therapies (p < 0.05). Furthermore, higher collagen curviness was associated with better outcomes, including a reduced recurrence risk (HR = 0.77, p < 0.001). Subtype-specific trends emerged as ER/PR-negative tumors more frequently exhibited a perpendicular collagen arrangement (p = 0.02), whereas ER/PR-positive tumors showed elevated COL1A1 expression (p < 0.0001). Despite these patterns, the heterogeneity of study methodologies and the complexity of the tumor microenvironment highlight the need for unified frameworks to advance clinical translation.</p><p><strong>Conclusions: </strong>This review highlights the prognostic significance of tumor-stromal collagen characteristics in breast cancer, suggesting that future research should focus on the molecular mechanisms underlying collagen remodeling and its potential as a cancer biomarker and therapeutic target.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"69"},"PeriodicalIF":7.4,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12054196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment and characterization of 24 breast cancer cell lines and 3 breast cancer organoids reveals molecular heterogeneity and drug response variability in malignant pleural effusion-derived models.","authors":"Soon-Chan Kim, Ga-Hye Kim, Jae-Hyeon Park, Kyung-Hun Lee, Jiwon Koh, Tae-Yong Kim, Dae-Won Lee, Yu-Jin Kim, Seongyeong Kim, Song-Yi Park, Ahrum Min, Young-Kyoung Shin, Seock-Ah Im, Ja-Lok Ku","doi":"10.1186/s13058-025-02032-7","DOIUrl":"https://doi.org/10.1186/s13058-025-02032-7","url":null,"abstract":"<p><p>Intratumoral heterogeneity of breast cancer cells causes undesired drug resistance and predispose to disease recurrence. We investigate the molecular heterogeneity of breast cancer cells derived from malignant pleural effusions (MPE) to understand variations in drug resistance and cellular evolution. MPE provides a unique environment, with cells experiencing significant microenvironmental changes that promote intratumoral heterogeneity and therapeutic resistance. By establishing 24 cell lines and 3 organoids from MPE samples of breast cancer patients, we performed extensive genomic, transcriptomic, and drug sensitivity analyses. Our findings reveal substantial genetic and transcriptomic diversity among MPE-derived cell lines, highlighting dynamic alterations in driver mutations and signaling pathways that correlate with variable drug responses. Notably, temporal and spatial heterogeneity within patient-derived samples emphasized the adaptability of breast cancer cells in MPE, as different subclones displayed distinct drug sensitivities. This work underscores the critical role of molecular profiling in understanding treatment resistance in breast cancer, presenting MPE-derived cell lines as valuable preclinical models for exploring personalized therapies in aggressive cancer phenotypes.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"66"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144005440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of minimal residual disease using the clonesight test for ultrasensitive ctDNA detection to anticipate late relapse in early breast cancer.","authors":"Iñaki Comino-Méndez, Jesús Velasco-Suelto, Javier Pascual, Esperanza López-López, Maria Elena Quirós-Ortega, Celia Gaona-Romero, Alejandro Martín-Muñoz, Patricia Losana, Yanira Heredia, Emilio Alba, Angel Guerrero-Zotano","doi":"10.1186/s13058-025-02016-7","DOIUrl":"https://doi.org/10.1186/s13058-025-02016-7","url":null,"abstract":"<p><strong>Background: </strong>Early-stage breast cancer (BC) diagnosis significantly reduces mortality, yet relapse remains a concern due to undetectable minimal residual disease (MRD). Liquid biopsies offer real-time insights into tumor dynamics, aiding MRD detection and therapy response evaluation. However, MRD detection is challenging due to low tumor DNA levels in circulation.</p><p><strong>Methods: </strong>This prospective study included 20 HR + BC patients who had completed at least 5 years of adjuvant endocrine therapy (ET). Plasma samples were collected every 6 months over a median follow-up period of 2 years. Tumor-specific somatic variants identified through tumor tissue sequencing served as biomarkers for a patient-informed circulating tumor DNA (ctDNA) assay (CloneSight), which utilized a multiplex PCR-based next-generation sequencing (NGS) workflow.</p><p><strong>Results: </strong>ctDNA was detected in patients who experienced clinical relapse, with positivity observed up to 68 months (5.7 years) prior to overt recurrence, highlighting its potential for early relapse identification. In non-relapsed patients, ctDNA remained undetectable in 93% of cases, reflecting a potential high level of specificity. The assay detected ctDNA in 50% of relapsed patients, while no ctDNA signal was identified in the majority of non-relapsed cases.</p><p><strong>Conclusion: </strong>Our exploratory findings indicate that CloneSight could be a promising tool for MRD detection and relapse prediction, providing a cost-effective, patient-informed approach to ctDNA monitoring. The ability of this approach to detect relapse prior to clinical recurrence suggests its potential relevance in improving patient monitoring. These findings suggest that ctDNA-based MRD assays could play a role in future surveillance strategies for HR + BC, though further studies in larger cohorts are needed to confirm their clinical applicability.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"65"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubule associated serine/threonine kinase-3 inhibits the malignant phenotype of breast cancer by promoting phosphorylation-mediated ubiquitination degradation of yes-associated protein.","authors":"Ning Deng, Wei Kang, Jiang Du, Xuezhu Rong, Qiang Han","doi":"10.1186/s13058-025-02028-3","DOIUrl":"https://doi.org/10.1186/s13058-025-02028-3","url":null,"abstract":"<p><strong>Background: </strong>Microtubule associated series/threonine kinase-3 (MAST3) is a member of microtubule associated serine/threonine kinase family (MAST1-4, MAST-like), and the expression and underlying molecular mechanism of MAST3 in human tumors, including breast cancer, is not yet elucidated.</p><p><strong>Methods: </strong>We employed immunohistochemistry to assess the significant expression of MAST3 in breast cancer tissue samples. Additionally, we utilized an overexpression vector and shRNA to bi-directionally regulate MAST3 expression, aiming to observe the impact of MAST3 on the proliferation, migration, and invasion capabilities of breast cancer cells. Furthermore, we employed immunoprecipitation, immunoblotting, luciferase reporter genes and real-time quantitative PCR to investigate the interaction between MAST3 and YAP, as well as the regulatory effects on the expression of Hippo pathway-related target genes.</p><p><strong>Results: </strong>Low MAST3 expression was observed both in breast cancer cells and tissues, which was significantly associated with advanced tumor T stage, lymph node metastasis, and poor patient prognosis. Functional experiments found that overexpression of MAST3 can gradually inhibit the proliferation and invasion of breast cancer cells, knocking-out MAST3 showed the opposite functional effect. Immunoprecipitation showed that MAST3 interacts with the key effector factor, yes-associated protein (YAP), in the Hippo pathway. The combination of MAST3-YAP promoted the phosphorylation of YAP, which led to its degradation through the ubiquitin-proteasome pathway and reduced nuclear translocation.</p><p><strong>Conclusions: </strong>MAST3 was identified as a novel tumor suppressor protein in breast cancer, which directly regulates the expression of YAP through the non-dependent mammalian sterile-20-like (MST)-large tumor suppressor (LATS) classical signaling pathway, providing a theoretical and experimental basis for the development of small-molecule tumor inhibitors in breast cancer.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"63"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12044935/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a risk prediction model for premenopausal breast cancer in 19 cohorts.","authors":"Kristen D Brantley, Michael E Jones, Rulla M Tamimi, Bernard A Rosner, Peter Kraft, Hazel B Nichols, Katie M O'Brien, Hans-Olov Adami, Amaia Aizpurua, Amy Berrington de Gonzalez, William J Blot, Tonje Braaten, Yu Chen, Jessica Clague DeHart, Laure Dossus, Sjoerd Elias, Renée T Fortner, Montserrat Garcia-Closas, Inger T Gram, Niclas Håkansson, Susan E Hankinson, Cari M Kitahara, Woon-Puay Koh, Martha S Linet, Robert J MacInnis, Giovanna Masala, Lene Mellemkjær, Roger L Milne, David C Muller, Hannah Lui Park, Kathryn J Ruddy, Sven Sandin, Xiao-Ou Shu, Sandar Tin Tin, Thérèse Truong, Celine M Vachon, Lars J Vatten, Kala Visvanathan, Elisabete Weiderpass, Walter Willett, Alicja Wolk, Jian-Min Yuan, Wei Zheng, Dale P Sandler, Minouk J Schoemaker, Anthony J Swerdlow, A Heather Eliassen","doi":"10.1186/s13058-025-02031-8","DOIUrl":"https://doi.org/10.1186/s13058-025-02031-8","url":null,"abstract":"<p><strong>Background: </strong>Incidence of premenopausal breast cancer (BC) has risen in recent years, though most existing BC prediction models are not generalizable to young women due to underrepresentation of this age group in model development.</p><p><strong>Methods: </strong>Using questionnaire-based data from 19 prospective studies harmonized within the Premenopausal Breast Cancer Collaborative Group (PBCCG), representing 783,830 women, we developed a premenopausal BC risk prediction model. The data were split into training (2/3) and validation (1/3) datasets with equal distribution of cohorts in each. In the training dataset variables were chosen from known and hypothesized risk factors: age, age at menarche, age at first birth, parity, breastfeeding, height, BMI, young adulthood BMI, recent weight change, alcohol consumption, first-degree family history of BC, and personal history of benign breast disease (BBD). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated by Cox proportional hazards regression using age as time scale, stratified by cohort. Given that complete information on all risk factors was not available in all cohorts, coefficients were estimated separately in groups of cohorts with the same available covariate information, adjusted to account for the correlation between missing and non-missing variables and meta-analyzed. Absolute risk of BC (in situ or invasive) within 5 years, was determined using country-, age-, and birth cohort-specific incidence rates. Discrimination (area under the curve, AUC) and calibration (Expected/Observed, E/O) were evaluated in the validation dataset. We compared our model with a literature-based model for women < 50 years (iCARE-Lit).</p><p><strong>Results: </strong>Selected model risk factors were age at menarche, parity, height, current and young adulthood BMI, family history of BC, and personal BBD history. Predicted absolute 5-year risk ranged from 0% to 5.7%. The model overestimated risk on average [E/O risk = 1.18 (1.14-1.23)], with underestimation of risk in lower absolute risk deciles and overestimation in upper absolute risk deciles [E/O 1st decile = 0.59 (0.58-0.60); E/O 10th decile = 1.48 (1.48-1.49)]. The AUC was 59.1% (58.1-60.1%). Performance was similar to the iCARE-Lit model.</p><p><strong>Conclusion: </strong>In this prediction model for premenopausal BC, the relative contribution of risk factors to absolute risk was similar to existing models for overall BC. The discriminatory ability was nearly identical (< 1% difference in AUC) to the existing iCARE-Lit model developed in women under 50 years. The inability to improve discrimination highlights the need to investigate additional predictors to better understand premenopausal BC risk.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"67"},"PeriodicalIF":7.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12046669/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}