NPJ Breast Cancer最新文献

{"title":"Breast cancer Intraoperative Margin Assessment using specimen PET-CT (BIMAP).","authors":"Anne-Sofie De Crem, Philippe Tummers, Herman Depypere, Geert Braems, Rawand Salihi, Glenn Vergauwen, Giovanni Cisternino, Koen Van de Vijver, Pieter De Visschere, Kathia De Man, Bliede Van den Broeck, Sigi Hendrickx, Liv Veldeman, Christel Monten, Jens M Debacker, Hannelore Denys, Menekse Göker","doi":"10.1038/s41523-025-00818-8","DOIUrl":"10.1038/s41523-025-00818-8","url":null,"abstract":"<p><p>Positive surgical margins in breast-conserving surgery (BCS) for breast cancer occur in 20% of cases, making intraoperative margin assessment (IMA) crucial to avoid re-operations. This study evaluated specimen PET-CT imaging for IMA in 41 patients undergoing BCS. Specimen PET-CT imaging was performed with the ß-CUBE/X-CUBE (MOLECUBES) or the AURA 10 (XEOS). Seven physicians, with varying experience, assessed margin status postoperatively as positive, close (≤1 mm), or negative using PET-CT images at 10 min acquisition time and low reconstructed [¹⁸F]FDG dose (0.8MBq/kg). Close margins on PET-CT were analyzed once as positive and once as negative. Histopathology was the gold standard. The proposed technique showed 91% sensitivity and 86% specificity for invasive ductal carcinoma (IDC). Histopathology identified 9 positive margins in 31 IDC cases; 88% were detected by all physicians on specimen PET-CT whereas standard of care identified 44%. Therefore, specimen PET-CT will improve IMA in BCS and potentially reduce re-operation rates. The trial is registered since 20/01/2020 on ClinicalTrials.gov (ID: NCT04343079) with the title: \"Intra-operative PET-CT: a Novel Approach to Determine Excision Margins in Lumpectomy Breast Cancer\".</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"101"},"PeriodicalIF":7.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12474864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Development and characterisation of a novel 3D in vitro model of obesity-associated breast cancer as a tool for drug testing.","authors":"Rhianna R R Blyth, Stèphanie A Laversin, Russell B Foxall, Constantinos Savva, Ellen Copson, Ramsey I Cutress, Charles N Birts, Stephen A Beers","doi":"10.1038/s41523-025-00823-x","DOIUrl":"10.1038/s41523-025-00823-x","url":null,"abstract":"","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"99"},"PeriodicalIF":7.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Personalized mutation tracking in circulating-tumor DNA predicts recurrence in patients with high-risk early breast cancer.","authors":"Sao Trung Nguyen, Van-Anh Nguyen Hoang, Vu Nguyen Trieu, Thanh Huyen Pham, Thi Cuc Dinh, Dinh Hoang Pham, Ngoc Nguyen, Dao Nguyen Vinh, Thanh Thuy Thi Do, Duy Sinh Nguyen, Hoai-Nghia Nguyen, Hoa Giang, Lan N Tu","doi":"10.1038/s41523-025-00825-9","DOIUrl":"10.1038/s41523-025-00825-9","url":null,"abstract":"","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"100"},"PeriodicalIF":7.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12433450/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing HER2-low breast cancer detection with quantitative transcriptomics.","authors":"Maria-Anna Misiakou, Maj-Britt Jensen, Maj-Lis Talman, Bent Ejlertsen, Maria Rossing","doi":"10.1038/s41523-025-00817-9","DOIUrl":"10.1038/s41523-025-00817-9","url":null,"abstract":"<p><p>Accurate identification of HER2-low breast cancers remains challenging using standard IHC. We analyzed 3182 breast tumors using transcriptomics, revealing detectable ERBB2 mRNA in 86% of IHC 0 cases. Pathological complete response was most prevalent in anti-HER2-treated patients with highest ERBB2 expression. Our results demonstrate that transcriptomics can sensitively detect HER2 expression and stratify patients beyond IHC classification, supporting its use as a complementary biomarker for guiding anti-HER2 therapy decisions.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"98"},"PeriodicalIF":7.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12402487/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 young age at metastatic breast cancer diagnosis and overall survival in the EMBRACE study.","authors":"Kristen D Brantley, Gregory J Kirkner, Melissa E Hughes, Leticia Varella, Georgia Suggs, Olivia M Cunningham, Sanjana Ravikumar, Craig Snow, Sara M Tolaney, Sarah Sammons, Ann H Partridge, Nancy U Lin","doi":"10.1038/s41523-025-00822-y","DOIUrl":"10.1038/s41523-025-00822-y","url":null,"abstract":"<p><p>The influence of young age at diagnosis on prognosis of patients with metastatic breast cancer (MBC) remains unclear. We examined overall survival (OS) within a single-institution prospective study of patients with de novo or recurrent MBC. Kaplan-Meier curves assessed OS by age (≤35 or ≤40 years as the youngest category) and inferred metastatic tumor subtype. Multivariable Cox regression models estimated hazard ratios (HRs) and 95% CIs for OS by age adjusting for clinical factors. Of 4189 women <75 years, 571 were ≤40 years at MBC diagnosis, of whom 260 were ≤35 years. Over half (52%) died during follow-up (median = 5.3 years, IQR = 2.1-9.8 years). Compared to patients 45-55 years, those ≤35 years at diagnosis experienced worse OS (HR = 1.22, 95%CI 1.00-1.48, p = 0.05). This association was driven by HER2-negative/luminal B-like and hormone receptor-positive/HER2-positive tumors. These findings highlight the need to develop more effective therapies for young patients with this metastatic subtype.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"96"},"PeriodicalIF":7.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic and predictive capacity of tumor infiltrating lymphocytes in the MA.20 regional node radiotherapy trial.","authors":"N Riaz, B E Chen, A Bane, D Gao, E S Stovgaard, Z Kos, S C Leung, E Shenasa, W Parulekar, S Chambers, T O Nielsen, T J Whelan","doi":"10.1038/s41523-025-00821-z","DOIUrl":"10.1038/s41523-025-00821-z","url":null,"abstract":"<p><p>Prognostic and predictive value of immune infiltrates in the context of regional nodal radiation (RNI) for breast cancer has not been assessed. Stromal tumor infiltrating lymphocytes (sTILs) were assessed on scanned images of hematoxylin and eosin (H&E) stained sections and by CD8 immunohistochemistry on tissue microarrays available from the MA.20 trial. Cox proportional modelling was used, and hazard ratios (HR) with 95% confidence intervals (CI) are reported for primary and secondary endpoints. Predictive value was assessed by an interaction test. H&E sTILs (continuous parameter) were prognostic for distant-DFS (HR 0.99, 95% CI 0.98-1.00, P = 0.04). CD8+sTILs were associated with significantly improved disease-free survival (DFS) (HR 0.99, 95% CI 0.98-1.00, P = 0.02) and distant-DFS (HR 0.98, 95% CI 0.97-0.99, P = 0.0002). CD8+sTILs was predictive of benefit from RNI for distant-DFS (continuous variable: HR 0.98, 95% CI 0.96-1.00, P_{(interaction)} = 0.04; exploratory categorical variable: CD8+ sTILs < 44, HR = 0.83; 95% CI 0.57-1.21, and CD8+ sTILs ≥ 44; HR 0.09; 95% CI 0.01-0.74, P_{(interaction)} = 0.04). In MA.20 breast cancer patients, pre-treatment sTILs were prognostic for DFS (CD8+sTILs) and distant-DFS. CD8+sTILs also appeared to be predictive for the effectiveness of RNI on distant-DFS, suggesting that immune mechanisms may in part be responsible and merits further investigation.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"97"},"PeriodicalIF":7.6,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12397239/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA sequencing reveals different cellular states in malignant cells and the tumor microenvironment in primary and metastatic ER-positive breast cancer.","authors":"Furkan Ozmen, Tugba Y Ozmen, Aysegul Ors, Mahnaz Janghorban, Matthew J Rames, Xi Li, Aaron Reid Doe, Fariba Behbod, Gordon B Mills, Hisham Mohammed","doi":"10.1038/s41523-025-00808-w","DOIUrl":"10.1038/s41523-025-00808-w","url":null,"abstract":"<p><p>Metastatic breast cancer remains largely incurable, and the mechanisms driving the transition from primary to metastatic breast cancer remain elusive. We analyzed the complex landscape of estrogen receptor (ER)-positive breast cancer primary and metastatic tumors using scRNA-seq data from twenty-three female patients with either primary or metastatic disease. By employing single-cell transcriptional profiling of unpaired patient samples, we sought to elucidate the genetic and molecular mechanisms underlying changes in the metastatic tumor ecosystem. We identified specific subtypes of stromal and immune cells critical to forming a pro-tumor microenvironment in metastatic lesions, including CCL2+ macrophages, exhausted cytotoxic T cells, and FOXP3+ regulatory T cells. Analysis of cell-cell communication highlights a marked decrease in tumor-immune cell interactions in metastatic tissues, likely contributing to an immunosuppressive microenvironment. In contrast, primary breast cancer samples displayed increased activation of the TNF-α signaling pathway via NF-kB, indicating a potential therapeutic target. Our study comprehensively characterizes the transcriptional landscape encompassing primary and metastatic breast cancer.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"95"},"PeriodicalIF":7.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144962972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteogenomic characterization of invasive breast tumors in young women.","authors":"Praveen-Kumar Raj-Kumar, Jianfang Liu, Anthony R Soltis, Nicholas W Bateman, Qingrong Chen, Lori A Sturtz, Brenda Deyarmin, Mariaelena Pierobon, Tamara A Abulez, Anupama Praveen-Kumar, Xijun Zhang, Trinh Nguyen, Chunhua Yan, Ying Hu, Kate Guion, Jeffrey A Hooke, Albert J Kovatich, Leigh Fantacone-Campbell, Brad Mostoller, Leonid Kvecher, Stella Somiari, Patricia S Steeg, Padma Sheila Rajagopal, Kathleen M Darcy, Jerry S H Lee, Clifton L Dalgard, Thomas P Conrads, Emanuel F Petricoin, Daoud Meerzaman, Matthew D Wilkerson, Xiaoying Lin, Craig D Shriver, Stanley Lipkowitz, Hai Hu","doi":"10.1038/s41523-025-00793-0","DOIUrl":"10.1038/s41523-025-00793-0","url":null,"abstract":"<p><p>Breast cancer in women <40, accounting for ~5% of all breast cancer cases diagnosed in the U.S., is more aggressive and associated with worse outcomes compared to breast cancer in older women. We performed a first-ever integrated proteogenomic study from a matched cohort of laser-microdissected tumors of 34 young (<40 years) and 34 older (≥60 years) women to identify molecular features that may underlie the worse outcomes in young women. Progression-free interval was shorter in young women, and their tumors were enriched for more aggressive molecular subtypes. Our multi-omic analysis identified distinct clusters between age groups in luminal but not basal-like cancers. Notably, GATA3 mutations were enriched in luminal tumors from young women while TP53 and PIK3CA mutations were more common in luminal tumors from older women. Young women's tumors exhibited lower estrogen receptor (ER) expression yet paradoxically enhanced ER response pathways and increased expression of tamoxifen-resistance-associated genes (IRS1, FERMT1). Immune pathway activity and immune scores were lower in tumors from young women, whereas proliferative and MYC pathways were notably elevated, identifying potential therapeutic targets. Transcriptomic data from TCGA and METABRIC confirmed our findings, with 10 of 11 observed pathways corroborated. Finally, differential expression of four immune-related surface proteins also suggested the potential of age-specific responses to immune-based therapies. Together, these findings may contribute to the understanding of the molecular mechanisms underlying worse outcomes in young women and offer new insight to therapeutic strategies.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"94"},"PeriodicalIF":7.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12361583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144874310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating genomic landscape following cyclin-dependent kinase 4/6 inhibitors exposure in HR + /HER2- metastatic breast cancer: a retrospective multi-institutional Consortium analysis.","authors":"Letizia Pontolillo, Andrew A Davis, Lorenzo Gerratana, Arielle J Medford, Judy Wang, Eleonora Nicolo', Katherine Clifton, Marko Velimirovic, Surbhi Warrior, Emily Podany, Eleni Andreopoulou, Mara Serena Serafini, Laura Munoz-Arcos, Elisabetta Molteni, Marla Lipsyc-Sharf, Caterina Gianni, Nadia Bayou, Charles S Dai, Diana Giannarelli, Emilio Bria, Cynthia X Ma, Aditya Bardia, Carolina Reduzzi, Massimo Cristofanilli","doi":"10.1038/s41523-025-00802-2","DOIUrl":"10.1038/s41523-025-00802-2","url":null,"abstract":"<p><p>Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) are the mainstay of treatment for hormone receptor positive, HER2 negative (HR + /HER2-) metastatic breast cancer (MBC). However, disease progression is inevitable and unveiling resistance mechanisms is crucial to guide post-CDK4/6i therapeutic strategies. In this study, we retrospectively analyzed a real-world, multi-institutional cohort of patients with HR + /HER2- MBC characterized by circulating tumor DNA (ctDNA) through next-generation sequencing (NGS) before starting second-line treatment. Among 93 patients previously treated with CDK4/6i, PIK3CA (37.6%), ESR1 (46.2%) and TP53 (31.2%) were the most altered genes. Comparing with a CDK4/6i plus ET naïve control cohort, ESR1 (p < 0.001) was significantly associated with first-line exposure. In multivariable analyses, PTEN alterations were independently associated with shorter progression free survival (PFS) (p = 0.008) and overall survival (OS) (p = 0.006), while TP53 (p = 0.031), CCDN1 (p = 0.003) and the ET second-line clinician's choice (p = 0.011) impacted the OS. Moreover, a low-mutant allele frequency was correlated to longer PFS (p = 0.017) and OS (p = 0.038). These findings highlight the prognostic relevance of specific molecular alterations and support the role of genomic profiling in guiding second-line treatment decisions after CDK4/6i therapy. Prospective validation is warranted to confirm the clinical utility of this approach in HR + /HER2 - MBC.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"93"},"PeriodicalIF":7.6,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357851/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bridging the gap: ctDNA, genomics, and equity in breast cancer care.","authors":"Julia Aronson, Manasa Bhatta, Lisa A Carey, Kunal Jobanputra, Gaorav P Gupta, Yara Abdou","doi":"10.1038/s41523-025-00811-1","DOIUrl":"10.1038/s41523-025-00811-1","url":null,"abstract":"<p><p>Circulating tumor DNA (ctDNA) has emerged as a powerful tool in precision oncology, offering a noninvasive approach to tumor profiling, minimal residual disease (MRD), and treatment monitoring. In breast cancer, ctDNA has shown promise in both metastatic and early-stage settings. However, its application and benefits have not been equitably realized across all populations. In this review, we examined the current evidence on ctDNA detection, assay performance, and clinical utility specifically within racially, ethnically, and geographically underrepresented populations. We synthesized data from genomic studies, ctDNA-based trials, and implementation research to identify disparities in ctDNA levels, mutational profiles, testing utilization, and access to genotype-matched therapies. These disparities were further compounded by structural barriers such as insurance coverage, geographic access, and limited inclusion in clinical research. Global data from low- and middle-income countries reinforced both the feasibility and the challenges of ctDNA implementation in resource-constrained settings. While ctDNA holds considerable potential to personalize breast cancer care, our findings underscore the urgent need to integrate equity into its validation, clinical application, and policy development to avoid perpetuating existing disparities.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"92"},"PeriodicalIF":7.6,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12357940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144862357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}