Breast Cancer Research最新文献

{"title":"Optimizing breast lesions diagnosis and decision-making with a deep learning fusion model integrating ultrasound and mammography: a dual-center retrospective study.","authors":"Ziting Xu, Shengzhou Zhong, Yang Gao, Jiekun Huo, Weimin Xu, Weijun Huang, Xiaomei Huang, Chifa Zhang, Jianqiao Zhou, Qing Dan, Lian Li, Zhouyue Jiang, Ting Lang, Shuying Xu, Jiayin Lu, Ge Wen, Yu Zhang, Yingjia Li","doi":"10.1186/s13058-025-02033-6","DOIUrl":"10.1186/s13058-025-02033-6","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to develop a BI-RADS network (DL-UM) via integrating ultrasound (US) and mammography (MG) images and explore its performance in improving breast lesion diagnosis and management when collaborating with radiologists, particularly in cases with discordant US and MG Breast Imaging Reporting and Data System (BI-RADS) classifications.</p><p><strong>Methods: </strong>We retrospectively collected image data from 1283 women with breast lesions who underwent both US and MG within one month at two medical centres and categorised them into concordant and discordant BI-RADS classification subgroups. We developed a DL-UM network via integrating US and MG images, and DL networks using US (DL-U) or MG (DL-M) alone, respectively. The performance of DL-UM network for breast lesion diagnosis was evaluated using ROC curves and compared to DL-U and DL-M networks in the external testing dataset. The diagnostic performance of radiologists with different levels of experience under the assistance of DL-UM network was also evaluated.</p><p><strong>Results: </strong>In the external testing dataset, DL-UM outperformed DL-M in sensitivity (0.962 vs. 0.833, P = 0.016) and DL-U in specificity (0.667 vs. 0.526, P = 0.030), respectively. In the discordant BI-RADS classification subgroup, DL-UM achieved an AUC of 0.910. The diagnostic performance of four radiologists improved when collaborating with the DL-UM network, with AUCs increased from 0.674-0.772 to 0.889-0.910, specificities from 52.1%-75.0 to 81.3-87.5% and reducing unnecessary biopsies by 16.1%-24.6%, particularly for junior radiologists. Meanwhile, DL-UM outputs and heatmaps enhanced radiologists' trust and improved interobserver agreement between US and MG, with weighted kappa increased from 0.048 to 0.713 (P < 0.05).</p><p><strong>Conclusions: </strong>The DL-UM network, integrating complementary US and MG features, assisted radiologists in improving breast lesion diagnosis and management, potentially reducing unnecessary biopsies.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"80"},"PeriodicalIF":7.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081494","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":"ESR1 testing on FFPE samples from metastatic lesions in HR + /HER2- breast cancer after progression on CDK4/6 inhibitor therapy.","authors":"Konstantinos Venetis, Giulia Cursano, Roberta Scafetta, Pier Paolo Maria Berton Giachetti, Alberto Concardi, Elisa De Camilli, Marianna D'Ercole, Eltjona Mane, Chiara Frascarelli, Antonio Marra, Sara Gandini, Francesco Pepe, Simone Scagnoli, Silvia Maria Rossi, Raffaella Troiano, Elena Speziale, Carmine De Angelis, Giancarlo Troncone, Umberto Malapelle, Giuseppe Perrone, Andrea Botticelli, Giuseppe Viale, Giuseppe Curigliano, Elena Guerini Rocco, Carmen Criscitiello, Nicola Fusco","doi":"10.1186/s13058-025-02020-x","DOIUrl":"https://doi.org/10.1186/s13058-025-02020-x","url":null,"abstract":"<p><p>Mutations in ESR1 play a critical role in resistance to endocrine therapy (ET) in hormone receptor-positive (HR +)/HER2- metastatic breast cancer (MBC). Testing for ESR1 mutations is essential for guiding treatment with novel oral selective estrogen receptor degraders (SERDs) like elacestrant or camizestrant. While most studies have utilized liquid biopsy (LB) for mutation detection, the role of formalin-fixed paraffin-embedded (FFPE) tissue biopsy in this context remains unclear. In this study, we analyzed a cohort of HR + /HER2- MBC patients who experienced resistance to ET and CDK4/6 inhibitors. Next-generation sequencing (NGS) was performed on FFPE biopsy samples obtained from metastatic sites at the time of disease progression. ESR1 mutations were detected in 24 out of 38 patients (63.2%), with p.D538G identified in 10 patients (45.5%) and p.Y537S in 6 patients (27.2%) as the most frequent alterations. One patient exhibited dual ESR1 mutations, and a recurrent ESR1-CCDC170 gene fusion was identified, underscoring the diversity and potential interplay of genetic alterations driving resistance in HR + /HER2- MBC. Notably, lung metastases were significantly more common in ESR1 mutant cases (8/24, 33.3%) compared to wild-type cases (1/14, 7.1%), while liver metastases showed no difference between mutant (12/24, 50.0%) and wild-type groups (7/14, 50.0%). Co-mutations in actionable pathways, particularly PIK3CA, were observed in n = 10 ESR1 mutant tumors (41.6%), highlighting their contribution to resistance mechanisms and posing significant challenges for treatment selection, as these alterations may necessitate combination therapies to effectively target multiple resistance pathways. This study presents new insights into the prevalence and clinical significance of ESR1 mutations in HR + /HER2- MBC, highlighting the potential utility of FFPE biopsy samples as a viable alternative or complementary approach to LB for mutation detection, particularly in resource-limited settings where access to ctDNA analysis may be constrained.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"79"},"PeriodicalIF":7.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081489","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":"Cancers missed, women dismissed yet persist: natural language processing of online forums.","authors":"Kathleene T Ulanday, Maxim Topaz, Jeanette Shekelle, Marley Gibbons, Desiree Walker, Paula M Castaño, Amanda Nixon, Stacy Lewis, Mary Beth Terry, Lauren C Houghton","doi":"10.1186/s13058-025-01985-z","DOIUrl":"10.1186/s13058-025-01985-z","url":null,"abstract":"<p><strong>Objective: </strong>To identify gaps and delays in the detection of early onset cancer.</p><p><strong>Methods: </strong>We examined firsthand experiences shared on an online discussion board hosted by the Young Survival Coalition-an advocacy group for young adults diagnosed with breast cancer-spanning the years 2009 to 2019. We used natural language processing to detect codes: \"first signs and symptoms,\" \"steps to diagnosis,\" \"healthcare interactions,\" \"patient-provider-system feelings,\" and \"staging/type.\" In the training dataset, we used qualitative content analysis to code text from 750 of the forum's 571,914 posts. We developed and evaluated automated approaches to quantify the proportion of codes in all posts. Lastly, we qualitatively reviewed the classified posts to identify areas for improvement along the clinical pathway.</p><p><strong>Results: </strong>The vast majority (81%) of young adults self-detected their breast cancer rather than the cancer being detected through a clinical breast exam. Young adults (70%) were dissatisfied with their care because they encountered delays at three crossroads along the clinical pathway: 1) whether the clinician ordered tests or dismissed the individual as too young; 2) whether imaging modalities were sensitive or not; 3) whether a biopsy confirmed or missed the cancer. Mental health challenges and parenting pressures compounded these delays. True positive cases who experienced these delays strongly encouraged their peers to self-advocate, persist and insist on further testing until diagnosed accurately.</p><p><strong>Conclusion: </strong>Dismissal and delays in diagnosis of early onset breast cancer mean potentially worse prognosis since later stage cancers are more aggressive with fewer treatment options. The perspectives from survivors highlight the need for more research informing early detection in young adults by considering breast awareness, use of MRI and ultrasound, biopsy referrals for exhibited breast symptoms in the absence of positive imaging, and sociomedical support for individuals in their role as current or future parent.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"78"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002894","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":"Association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasets.","authors":"Timothy J Robinson, Casey L Liveringhouse, Christopher Wilson, Sam Friedman, Justyn Nakashima, Matthew N Mills, Jacob D Purcell, Nicholas B Figura, Du Dongliang, Ram Thapa, Eric Welsh, Kamran A Ahmed, G Daniel Grass, Brooke L Fridley, Roberto Diaz","doi":"10.1186/s13058-025-01987-x","DOIUrl":"10.1186/s13058-025-01987-x","url":null,"abstract":"<p><strong>Background: </strong>Transcriptomic features of breast cancer locoregional recurrence (LRR) remain poorly understood. We therefore sought to investigate transcriptomic features associated with LRR in newly diagnosed invasive breast tumors from our institutional dataset.</p><p><strong>Methods: </strong>Transcriptomic profiling was performed on 632 tumors from consecutive patients treated within our health system for newly diagnosed non-metastatic breast cancer. Univariable Cox models identified genes whose expression was associated with LRR (q-value < 0.05). Up-regulated (UR) genes were defined as hazard ratio (HR) > 1 and down-regulated (DR) genes were defined as HR < 1. Gene set enrichment analyses were performed for UR and DR gene sets and validated within two external cohorts of ER- tumors.</p><p><strong>Results: </strong>With a median follow-up of 7.6 years, we observed 38 LRRs: 28/481 (5.8%) in ER + and 10/151 (6.6%) in ER-. There were 43 UR and 7 DR genes associated with LRR in ER + tumors, while 417 UR and 1150 DR genes were associated with LRR in ER- tumors. UR genes in ER + tumors were enriched for roles in cell proliferation (q < 0.05). In contrast, LRR in ER- tumors was most strongly associated with DR genes enriched for MHC-II-mediated antigen presentation and T cell activation (q < 0.05). In external cohorts of ER- tumors, 97 significant DR genes (p < 0.05) were enriched for 18 pathways, including 5 pathways involved in MHC-II signaling, antigen presentation and T-cell activation.</p><p><strong>Conclusions: </strong>Transcriptomic patterns associated with LRR appear distinct between ER + and ER- tumors. In ER + tumors, LRR appears predominantly associated with proliferation, whereas ER- LRR suggests a robust pattern of suppressed antigen presentation via MHC-II.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"77"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023940","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":"Retraction Note: Tamoxifen suppresses brain metastasis of estrogen receptor-deficient breast cancer by skewing microglia polarization and enhancing their immune functions.","authors":"Shih-Ying Wu, Sambad Sharma, Kerui Wu, Abhishek Tyagi, Dan Zhao, Ravindra Pramod Deshpande, Kounosuke Watabe","doi":"10.1186/s13058-025-02042-5","DOIUrl":"10.1186/s13058-025-02042-5","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"75"},"PeriodicalIF":7.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046828","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":"Prognostic value of cancer-related fatigue at the end of radiotherapy for overall survival ≥ 10 years in women with breast cancer.","authors":"Philipp Heumann, Axel Benner, Sabine Behrens, Jenny Chang-Claude, Petra Seibold","doi":"10.1186/s13058-025-02036-3","DOIUrl":"10.1186/s13058-025-02036-3","url":null,"abstract":"<p><strong>Background: </strong>Cancer-related fatigue (CRF) is a common symptom in breast cancer patients and survivors, which can substantially impair quality of life. Previous studies suggested that CRF may be associated with poorer survival outcomes, but had limited follow-up duration or insufficient adjustment for established prognostic factors. The aim of this analysis was to assess the prognostic value of CRF at the end of radiotherapy for overall survival in a cohort of women with breast cancer with a median follow-up time of 19 years.</p><p><strong>Methods: </strong>Data from the prospective ISE study, which enrolled women with non-metastatic breast cancer between 1998 and 2001, were analysed. Patients did not receive chemotherapy. A vital status follow-up was conducted in 2019. CRF was collected at the end of radiotherapy using the EORTC QLQ-C30 and classified using the threshold of clinical importance. Cox regression models adjusted for CRF, age, body mass index (BMI), tumour size, nodal involvement, grading and receptor status were calculated.</p><p><strong>Results: </strong>Of 437 patients with fatigue assessments, 164 (38%) reported CRF. During 10 years of follow-up, 25 patients without and 27 patients with CRF died. Tumour size, nodal involvement and age were statistically significantly associated with 10-year overall survival. For CRF, a statistically significant effect was observed for ≥ 5 years of follow-up (HR: 2.44), but not within the first 5 years of follow-up (HR: 1.26).</p><p><strong>Conclusions: </strong>CRF assessments at the end of radiotherapy showed prognostic value for long-term survival beyond established factors and could potentially be used to identify patients that require monitoring in risk-adapted aftercare programmes in order to improve survival.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"76"},"PeriodicalIF":7.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046826","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":"Denosumab as an immune modulator in HER2-negative early breast cancer: results of the window-of-opportunity D-BIOMARK clinical trial.","authors":"Andrea Vethencourt, Eva M Trinidad, Eduard Dorca, Anna Petit, M Teresa Soler-Monsó, Marina Ciscar, Alexandra Barranco, Gema Pérez-Chacón, María Jimenez, Mario Rodríguez, Clara Gomez-Aleza, Elvira Purqueras, Enrique Hernández-Jiménez, Ander Urruticoechea, Idoia Morilla, Isaac Subirana, Amparo García-Tejedor, Miguel Gil-Gil, Sonia Pernas, Catalina Falo, Eva Gonzalez-Suarez","doi":"10.1186/s13058-025-01996-w","DOIUrl":"10.1186/s13058-025-01996-w","url":null,"abstract":"<p><strong>Background: </strong>The RANK pathway has been extensively investigated for its role in bone resorption; however, its significance extends beyond bone metabolism. Preclinical models suggest that inhibition of RANK signaling can prevent mammary tumor development by reducing proliferation and tumor cell survival. Additionally, both preclinical and clinical data support the ability of RANK pathway inhibitors to enhance the anti-tumor immune response.</p><p><strong>Methods: </strong>D-BIOMARK is a prospective, randomized window-of-opportunity clinical trial assessing the biological effects of denosumab, a monoclonal antibody against RANKL, in patients with HER2-negative early breast cancer. The study aims to assess denosumab's impact on breast tumor cell proliferation, apoptosis, and its potential to influence the tumor immune microenvironment. A total of 60 patients were enrolled and randomized 2:1 to receive two doses of single agent denosumab (120 mg one week apart) before surgery or to the control arm (no treatment). Fifty-eight patients were evaluated, 27 pre-menopausal and 31 post-menopausal women, 48 with luminal tumors and 10 with triple negative breast cancer. Paired tumor samples were collected to compare baseline (core biopsy) and surgical (surgical specimen) time points, as well as serum samples at both time points.</p><p><strong>Results: </strong>Denosumab demonstrated its ability to reduce serum free RANKL levels (experimental p < 0.001, control p = 0.270). However, a reduction in tumor cell proliferation or cell survival was not observed. A denosumab-driven increase in tumor infiltrating lymphocytes (TILs) was observed (experimental p = 0.001, control p = 0.060), particularly in the luminal B-like population (experimental p = 0.012, control p = 0.070) and a similar trend in the TNBC group (experimental p = 0.079, control p = 0.237). Denosumab led to increased TILs in both pre-menopausal (experimental p = 0.048, control p = 0.639) and post-menopausal (experimental p = 0.041, control p = 0.062) women with luminal tumors. RANK protein expression in tumor and stroma was associated with markers of tumor aggressiveness but an increase in TILs was observed in the experimental arm, irrespectively of RANK and RANKL expression in tumor or stromal cells.</p><p><strong>Conclusions: </strong>The D-BIOMARK trial suggests a potential role for denosumab as an immune-enhancing agent in early HER2-negative breast cancer. Although preoperative denosumab did not reduce tumor proliferation or increased apoptosis, it led to an increase in TILs, particularly in luminal B-like tumors. These findings underscore the importance of further investigation into the multifaceted aspects of the RANK pathway. Trial registration EudraCT number: 2016-002678-11 registered on June 15, 2018.</p><p><strong>Clinicaltrials: </strong>gov identifier: NCT03691311, retrospectively registered on September 04, 2018.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"68"},"PeriodicalIF":7.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053628","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":"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":"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}