NPJ Breast Cancer最新文献

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Proteomic signatures identify significantly different inflammatory breast tissue microenvironments depending on mammographic density or estrogen exposure. 蛋白质组学特征识别显著不同的炎性乳腺组织微环境取决于乳房x线摄影密度或雌激素暴露。
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-09-04 DOI: 10.1038/s41523-026-01046-4
Menikae K Heenkenda, Annelie Abrahamsson, Peter Lundberg, Charlotta Dabrosin
{"title":"Proteomic signatures identify significantly different inflammatory breast tissue microenvironments depending on mammographic density or estrogen exposure.","authors":"Menikae K Heenkenda, Annelie Abrahamsson, Peter Lundberg, Charlotta Dabrosin","doi":"10.1038/s41523-026-01046-4","DOIUrl":"10.1038/s41523-026-01046-4","url":null,"abstract":"<p><p>Breast density and estrogen exposure are two major risk factors for breast cancer; however, the underlying biological mechanisms remain incompletely understood. Here, we investigated the extracellular proteomic landscape of normal human breast tissue in situ to define the microenvironment associated with these risk factors. Forty-two postmenopausal women with nondense or dense breasts and 19 premenopausal women underwent microdialysis. We quantified 461 inflammatory proteins in breast tissue and matched subcutaneous fat, enabling discrimination between local and systemic alterations. Breast density was assessed using magnetic resonance imaging. Dense breast tissue exhibited a distinct protein signature characterized by immune-related signaling, altered lipid metabolism, and the extracellular presence of intracellular proteins, consistent with cellular stress and immune modulation, with limited changes in angiogenic and extracellular matrix remodeling proteins. In contrast, estrogen-exposed breasts displayed a proteomic profile dominated by pro-inflammatory cytokines, angiogenic factors, extracellular matrix remodeling proteins, and complement activation, indicative of a dynamic and pro-tumorigenic microenvironment. These findings demonstrate that breast density and estrogen exposure are associated with fundamentally distinct breast microenvironments, both permissive for tumor progression. These breast-specific protein signatures provide mechanistic insight into how these risk factors contribute to cancer development and suggest that effective prevention strategies may require differential targeting.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"12 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13545232/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891034","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}
引用次数: 0
Genomic characterization of ER-positive primary tumors and corresponding relapses identifies potentially targetable alterations. er阳性原发性肿瘤和相应复发的基因组特征确定了潜在的靶向改变。
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-08-30 DOI: 10.1038/s41523-026-01041-9
Caroline Schagerholm Stanev, Stephanie Robertson, Hosein Toosi, Emmanouil G Sifakis, Jens Lagergren, Johan Hartman
{"title":"Genomic characterization of ER-positive primary tumors and corresponding relapses identifies potentially targetable alterations.","authors":"Caroline Schagerholm Stanev, Stephanie Robertson, Hosein Toosi, Emmanouil G Sifakis, Jens Lagergren, Johan Hartman","doi":"10.1038/s41523-026-01041-9","DOIUrl":"10.1038/s41523-026-01041-9","url":null,"abstract":"<p><p>The majority of breast cancer patients have tumors expressing estrogen receptor α (ER) and receive endocrine therapy. However, around one-third relapse in their disease, predominantly with retained ER expression. Molecular alterations are proposed to be contributors to the resistance mechanisms. Patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative primary breast cancer with an ER-positive relapse < 5 years of ongoing endocrine therapy were retrospectively assessed. Extracted DNA was analyzed through panel sequencing, and RNA by microarray, from patients' primary (n = 58), and paired relapse tumors (n = 54), and tumor-free lymph nodes (DNA germline controls, n = 62). Several single-nucleotide variations and copy number variations showed nominal exploratory associations with worse overall survival. Copy number correlations with intrinsic subtypes and individual gene expression supported the findings. These results identify hypothesis-generating genomic and transcriptomic features, including potentially targetable alterations, in a clinically defined cohort of endocrine-resistant breast cancer patients.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"12 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148857502","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}
引用次数: 0
DynamicBUS: restoring temporal dynamics from static ultrasound for improved breast cancer diagnosis. DynamicBUS:从静态超声恢复时间动态以改善乳腺癌诊断。
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-08-28 DOI: 10.1038/s41523-026-01038-4
Zhikai Yang, Yaofang Liu, Tianhao Bai, Ander Biguri, Haoyuan Chen, Yonghao Li, Carola-Bibiane Schönlieb, Örjan Smedby, Raymond Chan, Rodrigo Moreno
{"title":"DynamicBUS: restoring temporal dynamics from static ultrasound for improved breast cancer diagnosis.","authors":"Zhikai Yang, Yaofang Liu, Tianhao Bai, Ander Biguri, Haoyuan Chen, Yonghao Li, Carola-Bibiane Schönlieb, Örjan Smedby, Raymond Chan, Rodrigo Moreno","doi":"10.1038/s41523-026-01038-4","DOIUrl":"10.1038/s41523-026-01038-4","url":null,"abstract":"<p><p>The clinical practice of archiving static 2D images from dynamic breast ultrasound (BUS) examinations loses vital temporal information, limiting computer-aided diagnosis systems. We challenge this constraint by proposing a novel framework that computationally recovers lost temporal dynamics to enhance diagnostic accuracy. Our framework first synthesizes a BUS video from a static key frame using a purpose-built generative model. We introduce a key-frame conditioning strategy to ensure the anatomical fidelity of the lesion is preserved while generating useful dynamic cues. Subsequently, the high-fidelity static image and the synthesized video are fed into Image Video network(IV-Net), a dual-branch fusion network that integrates pristine spatial details with recovered temporal context for robust classification. Evaluated on internal and external datasets, our framework outperforms methods relying solely on static images, achieving AUC of 94.13% and 82.55%, respectively. Furthermore, a reader study indicates the generated videos are indistinguishable to experts and improve diagnostic performance. Overall, our method demonstrates generative model potential to restore lost information, paving the way for reliable BUS diagnostics.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"12 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840923","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}
引用次数: 0
Genome-wide DNA methylation profiling of triple-negative breast cancer uncovers epigenetic biomarkers of tumor identity and the immune microenvironment. 三阴性乳腺癌的全基因组DNA甲基化分析揭示了肿瘤身份和免疫微环境的表观遗传生物标志物。
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-08-12 DOI: 10.1038/s41523-026-01030-y
Iñaki Sasiain, Deborah F Nacer, Mats Jönsson, Johan Vallon-Christersson, Anita Grigoriadis, Mattias Aine, Johan Staaf
{"title":"Genome-wide DNA methylation profiling of triple-negative breast cancer uncovers epigenetic biomarkers of tumor identity and the immune microenvironment.","authors":"Iñaki Sasiain, Deborah F Nacer, Mats Jönsson, Johan Vallon-Christersson, Anita Grigoriadis, Mattias Aine, Johan Staaf","doi":"10.1038/s41523-026-01030-y","DOIUrl":"10.1038/s41523-026-01030-y","url":null,"abstract":"<p><p>DNA methylation deregulation is an essential feature of tumor biology, influencing cancer formation and pathogenesis. Analyses of DNA methylation in bulk cancer specimens are challenging due to the high data dimensionality, noise, and mixture of different cell types. Here, we characterized methylation dynamics in cancer by investigating the variance structure of bulk tumor DNA methylation data through the identification of groups of highly correlated CpGs, termed CpG cassettes. Using triple-negative breast cancer as a model system, our approach identified co-occurring methylation patterns linked to different intrinsic tumor processes and pathways, gene inactivation, and composition of the tumor immune microenvironment. Our framework also demonstrated the presence of high-variance DNA methylation, seemingly not linked to tumor biology, that could be excluded using chromatin accessibility filtering. Together, this work outlines a comprehensive approach to analyze bulk tumor DNA methylation data, combining tumor purity adjustment, functional CpG filtering, stratification by CpG contexts, and identification of highly correlated CpG modules to enhance tumor-intrinsic DNA methylation patterns and our understanding of processes shaping epigenetic tumor evolution.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"12 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13469125/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148726816","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}
引用次数: 0
Circulating tumor DNA as an arbitrator for postmastectomy radiotherapy: bridging molecular residual disease and locoregional control. 循环肿瘤DNA作为乳房切除术后放射治疗的仲裁者:桥接分子残留疾病和局部控制。
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-07-29 DOI: 10.1038/s41523-026-01013-z
Gai Liang, Qu Zhang, Mengting Yuan, Guojun Yao, Feng Yuan
{"title":"Circulating tumor DNA as an arbitrator for postmastectomy radiotherapy: bridging molecular residual disease and locoregional control.","authors":"Gai Liang, Qu Zhang, Mengting Yuan, Guojun Yao, Feng Yuan","doi":"10.1038/s41523-026-01013-z","DOIUrl":"10.1038/s41523-026-01013-z","url":null,"abstract":"","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"12 1","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13421472/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148619933","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}
引用次数: 0
The WinPro trial: window-of-opportunity study of endocrine therapy with micronised progesterone in ER-positive breast cancer. WinPro试验:雌激素受体阳性乳腺癌微孕酮内分泌治疗的机会之窗研究。
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-07-21 DOI: 10.1038/s41523-026-01008-w
Lucy Haggstrom, Kate Middleton, Andrew Parker, Davendra Segara, Andrew Ong, Janne Bingham, Emma-Kate Carson, Belinda E Kiely, Dhanusha Sabanathan, Andrew Spillane, Kate Saw, Aura Serrano, Geoffrey J Lindeman, Alexander Swarbrick, Alan Coates, G Bruce Mann, Wayne Tilley, Elgene Lim
{"title":"The WinPro trial: window-of-opportunity study of endocrine therapy with micronised progesterone in ER-positive breast cancer.","authors":"Lucy Haggstrom, Kate Middleton, Andrew Parker, Davendra Segara, Andrew Ong, Janne Bingham, Emma-Kate Carson, Belinda E Kiely, Dhanusha Sabanathan, Andrew Spillane, Kate Saw, Aura Serrano, Geoffrey J Lindeman, Alexander Swarbrick, Alan Coates, G Bruce Mann, Wayne Tilley, Elgene Lim","doi":"10.1038/s41523-026-01008-w","DOIUrl":"https://doi.org/10.1038/s41523-026-01008-w","url":null,"abstract":"<p><p>Progesterone can inhibit tumoural proliferation in oestrogen receptor positive (ER+) breast cancer. The WinPro trial (Australian New Zealand Trials Clinical Trials Registry number: ACTRN12618000928213, date of registration 01/06/2018) was a randomised, multi-centre, phase 2, window-of-opportunity trial evaluating micronised progesterone (MP) in post-menopausal women with early-stage, ER+, progesterone receptor (PR) positive, HER2- breast cancer. Patients were randomised to letrozole, letrozole and MP, or tamoxifen and MP for 14 days preoperatively. The primary endpoint was the percent proportional reduction in Ki67 ('Ki67 suppression') between the two letrozole groups in the per protocol population. From February 2018 to June 2024, 244 patients were enrolled. 189 patients completed per protocol: letrozole (n = 66, 34.9%), letrozole + MP (n = 64, 33.9%), and tamoxifen + MP (n = 59, 31.2%). There was no difference in Ki67 suppression between letrozole (88.2%) versus letrozole + MP (89.2%) (p = 0.39). Ki67 suppression appeared lower with tamoxifen + MP (61.5%). Hot flushes appeared less frequent with letrozole + MP (13.3%) versus letrozole (22.4%) or tamoxifen + MP (20.5%).</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Novel (Z)-endoxifen-related new chemical entities exhibit potent anti-cancer activity in ERα+ breast cancer. 新的(Z)-内毒素相关的新化学实体在ERα+乳腺癌中显示出强大的抗癌活性。
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-07-20 DOI: 10.1038/s41523-026-01007-x
Lena Batoon, Rajeev S Muthyala, Xiyin Wang, Esther Rodman, Michael Emch, Sofia Marigliano, Anna Detry, Sandra S Hammer, Mohsen Sadatrezaei, Steven C Quay, Matthew P Goetz, John R Hawse
{"title":"Novel (Z)-endoxifen-related new chemical entities exhibit potent anti-cancer activity in ERα+ breast cancer.","authors":"Lena Batoon, Rajeev S Muthyala, Xiyin Wang, Esther Rodman, Michael Emch, Sofia Marigliano, Anna Detry, Sandra S Hammer, Mohsen Sadatrezaei, Steven C Quay, Matthew P Goetz, John R Hawse","doi":"10.1038/s41523-026-01007-x","DOIUrl":"https://doi.org/10.1038/s41523-026-01007-x","url":null,"abstract":"<p><p>Approximately 80% of breast cancers express estrogen receptor alpha (ERα), yet ERα-positive disease remains associated with high recurrence and late relapse. (Z)-Endoxifen (ENDX), the most abundant active metabolite of tamoxifen, is a potent, orally bioavailable, selective estrogen receptor modulator currently in development for breast health indications. During its synthesis, structurally related compounds are generated as byproducts termed here as new chemical entities (NCEs): AT416E, AT416Z, AT402E, AT402Z, and AT300, which have not been previously studied. We evaluated these NCEs alongside ENDX using multiple ERα-positive breast cancer cell lines, including models harboring clinically relevant ESR1 mutations. Activity was assessed using 2D and 3D proliferation, apoptosis, cell cycle profiling, migration, invasion, ERα transcriptional activity, RNA sequencing and synergy with abemaciclib. Several NCEs exhibited potent anti-estrogenic and anti-cancer effects. In various settings, these compounds matched or exceeded ENDX's activity, highlighting their therapeutic promise. RNA sequencing analysis revealed both shared and compound-specific transcriptional programs. Some NCEs also combined favorably with abemaciclib, producing additive to synergistic effects comparable to or greater than ENDX. Together, our findings support further investigation of select NCEs for ERα-positive breast cancer, particularly for tumors with ESR1 activating mutations and as potential second- or third-line options for recurrent disease.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Ensemble machine learning for predicting breast cancer recurrence and mortality using clinical and hemogram data. 使用临床和血象数据预测乳腺癌复发和死亡率的集成机器学习。
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-07-11 DOI: 10.1038/s41523-026-01005-z
Patricia Honorato Moreira, Arthur Shuzo Owtake Cardoso, Rafael de Oliveira, Joaquim Gasparini Dos Santos, Renata Colombo Bonadio, Wesley Antonio Lopes de Lima, Thomas de Almeida Reichmann, Bruna Salani Mota, Alexandre Ferreira Ramos, Flavia Santoro, Roger Chammas, Luciana Rodrigues Carvalho Barros
{"title":"Ensemble machine learning for predicting breast cancer recurrence and mortality using clinical and hemogram data.","authors":"Patricia Honorato Moreira, Arthur Shuzo Owtake Cardoso, Rafael de Oliveira, Joaquim Gasparini Dos Santos, Renata Colombo Bonadio, Wesley Antonio Lopes de Lima, Thomas de Almeida Reichmann, Bruna Salani Mota, Alexandre Ferreira Ramos, Flavia Santoro, Roger Chammas, Luciana Rodrigues Carvalho Barros","doi":"10.1038/s41523-026-01005-z","DOIUrl":"https://doi.org/10.1038/s41523-026-01005-z","url":null,"abstract":"<p><p>Accurate prediction of breast cancer recurrence remains difficult because prognosis varies significantly across molecular subtypes. This underscores the need for scalable, affordable, and interpretable prognostic tools. We developed machine learning models integrating hematological indices with clinicopathologic data to predict 2- and 10-year recurrence or all-case death. We retrospectively analyzed 4277 women with primary breast cancer (2008-2022). The cohort included hormone receptor-positive (HR + ), HER2-positive, and triple-negative (TNBC) subtypes. We trained multiple classifiers and integrated them into a stacked ensemble using logistic regression as the final learner. Class imbalance was addressed with SMOTE applied to training sets. The ensemble achieved strong discrimination: general cohort AUC 0.859 (2-year) and 0.811 (10-year), with specificity 84-82% and sensitivity 68-61%. Subtype-specific performance remained robust across time horizons: HR + AUC 0.862/0.804, HER2 + AUC 0.877/0.831, and TNBC AUC 0.826/0.826 (2-year/10-year respectively). SHAP analysis identified advanced tumor stage, elevated inflammatory ratios (NLR, PLR, MLR), elevated red cell distribution width, and age as key adverse predictors with stronger effects on early recurrence. This interpretable tool uses routine blood tests and clinico-pathological data at diagnosis. It flaggs high-risk patients for intensified therapy, useful where genomic testing is unavailable.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Routine germline genetic testing in 3552 unselected NHS breast cancer patients: evidence informing testing criteria and implementation of a 'BRCA-DIRECT' mainstreaming pathway. 3552例未选择的NHS乳腺癌患者的常规生殖系基因检测:检测标准和“BRCA-DIRECT”主流途径实施的证据
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-07-09 DOI: 10.1038/s41523-026-01000-4
Bethany Torr, Lea Mansour, Caitlin T Fierheller, Monica Hamill, Joshua Nolan, Nicola Bell, Subin Choi, Sophie Allen, Sudeekshna Muralidharan, Suzanne MacMahon, Yasmin Clinch, Mikel Valganon-Petrizan, Helena Harder, Alice Garrett, D Gareth Evans, Angela George, Valerie Jenkins, Lesley Fallowfield, Rosa Legood, Zoe Kemp, Ranjit Manchanda, Clare Turnbull
{"title":"Routine germline genetic testing in 3552 unselected NHS breast cancer patients: evidence informing testing criteria and implementation of a 'BRCA-DIRECT' mainstreaming pathway.","authors":"Bethany Torr, Lea Mansour, Caitlin T Fierheller, Monica Hamill, Joshua Nolan, Nicola Bell, Subin Choi, Sophie Allen, Sudeekshna Muralidharan, Suzanne MacMahon, Yasmin Clinch, Mikel Valganon-Petrizan, Helena Harder, Alice Garrett, D Gareth Evans, Angela George, Valerie Jenkins, Lesley Fallowfield, Rosa Legood, Zoe Kemp, Ranjit Manchanda, Clare Turnbull","doi":"10.1038/s41523-026-01000-4","DOIUrl":"https://doi.org/10.1038/s41523-026-01000-4","url":null,"abstract":"<p><p>In the North Thames Mainstreaming of Breast Cancer Genetic Testing (NT-MBGT) programme, we piloted testing for breast cancer susceptibility genes (BCSGs) in unselected breast cancer (BC) patients, deploying a clinician-light 'BRCA-DIRECT' mainstreaming pathway; this included home saliva-testing and consent with postal return, written and digital materials, with full access to a Genetic Counsellor Telephone helpline. Across 14 National Health Service (NHS) breast oncology units, we successfully tested 3515 newly-diagnosed BC patients with high levels of patient and breast healthcare professional (HCP) satisfaction and genetics HCPs reporting decreases in service referrals. The pick-up rate of gPVs was 4.7% (166 germline Pathogenic Variants (gPVs) across seven BCSGs). Examining application of current NHS eligibility criteria to the unselected cohort, testing would have been offered to 20.6% of patients with identification of 49.2% of gPVs in high penetrance (HP)-BCSGs (BRCA1/BRCA2/PALB2) and 18.2% of gPVs in intermediate penetrance-BCSGs (CHEK2/ATM/RAD51C/RAD51D). Designing 'Ultra-simple' eligibility criteria suitable for mainstreaming, detection (sensitivity) could be improved to 81.1% and 70.4% respectively, whilst increasing testing to 49.7% of BC cases. Evidence from the NT-MBGT programme demonstrates that expanding BCSG-testing via a clinician-light pathway is acceptable and feasible, without increasing the burden on limited breast and genetics workforce, and has high satisfaction.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422901","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Impact of neoadjuvant chemotherapy on local breast microbiota and macrophages in ER-positive breast cancer with links to treatment response. 新辅助化疗对er阳性乳腺癌局部乳腺微生物群和巨噬细胞的影响及其与治疗反应的关系
IF 8.4 2区 医学
NPJ Breast Cancer Pub Date : 2026-07-06 DOI: 10.1038/s41523-026-01004-0
Sabine Dieleman, Carlijn Bruggeling, Phuc Dat Le, Lars E Hillege, Catarina Correia Tavares Bernardino, Janine Ziemons, Renske Cremers, Arnaud Jacquerie, Alem Gusinac, Thomas H A Ederveen, Kiek Verrijp, John Penders, Anne-Marie Vos, Loes F S Kooreman, Heike I Grabsch, Marjolein L Smidt, Annemarie Boleij
{"title":"Impact of neoadjuvant chemotherapy on local breast microbiota and macrophages in ER-positive breast cancer with links to treatment response.","authors":"Sabine Dieleman, Carlijn Bruggeling, Phuc Dat Le, Lars E Hillege, Catarina Correia Tavares Bernardino, Janine Ziemons, Renske Cremers, Arnaud Jacquerie, Alem Gusinac, Thomas H A Ederveen, Kiek Verrijp, John Penders, Anne-Marie Vos, Loes F S Kooreman, Heike I Grabsch, Marjolein L Smidt, Annemarie Boleij","doi":"10.1038/s41523-026-01004-0","DOIUrl":"https://doi.org/10.1038/s41523-026-01004-0","url":null,"abstract":"<p><p>Gut microbiota can modulate the tumor microenvironment and influence therapeutic outcomes in breast cancer. We hypothesized that similar interactions occur between the breast microbiota and tumor microenvironment. This exploratory study evaluated whether in situ microbial and macrophage densities differ between good and poor neoadjuvant chemotherapy responders and compared microbial density and composition post treatment with surgery-only controls. In 20 postmenopausal estrogen receptor-positive breast cancer patients, bacterial density was quantified by fluorescence in situ hybridization and macrophages density by multiplexed immunofluorescence in pre and post treatment tissue. Bacterial composition was analyzed by 16S rRNA sequencing of post-treatment resection specimens. Nine surgery-only patients served as controls. Neoadjuvant chemotherapy significantly reduced CD68 macrophage density, but not CD163 macrophages or bacterial density. Macrophages and bacterial densities were not correlated, and bacterial densities did not differ between good and poor responders. Higher pretreatment CD68 and CD163 macrophage densities predicted good response. Post treatment resections showed reduced bacterial density and alpha-diversity compared to surgery-only controls. These findings suggest that neoadjuvant chemotherapy affects local breast microbiota and macrophages, with macrophages as promising biomarkers to predict treatment response. The interaction between breast microbiota and local immunity deserves more attention in future research.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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