NPJ Breast Cancer最新文献_第5页

Genomic landscape of breast cancer in elderly patients. 老年乳腺癌患者的基因组图谱。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-10 DOI: 10.1038/s41523-025-00781-4

Pier Selenica, Higinio Dopeso, Matteo Repetto, Thais Basili, Andrea M Gazzo, Christopher J Schwartz, Fatemeh Derakhshan, Antonio Marra, Lorenzo Ferrando, Regina G H Beets-Tan, Y H Wen, Dara S Ross, Edi Brogi, Hong Zhang, Larry Norton, Sarat Chandarlapaty, Pedram Razavi, Diana Mandelker, Jorge S Reis-Fiho, Britta Weigelt, Fresia Pareja

{"title":"Genomic landscape of breast cancer in elderly patients.","authors":"Pier Selenica, Higinio Dopeso, Matteo Repetto, Thais Basili, Andrea M Gazzo, Christopher J Schwartz, Fatemeh Derakhshan, Antonio Marra, Lorenzo Ferrando, Regina G H Beets-Tan, Y H Wen, Dara S Ross, Edi Brogi, Hong Zhang, Larry Norton, Sarat Chandarlapaty, Pedram Razavi, Diana Mandelker, Jorge S Reis-Fiho, Britta Weigelt, Fresia Pareja","doi":"10.1038/s41523-025-00781-4","DOIUrl":"10.1038/s41523-025-00781-4","url":null,"abstract":"Breast cancer (BC) displays age-related histopathologic and transcriptomic heterogeneity. Whether BC in elderly patients differs genetically from that of younger individuals remains unclear. We re-analyzed sequencing data from 1918 BCs previously subjected to an FDA-cleared paired tumor-normal targeted sequencing assay across elderly (≥65 years), middle-aged (>45 and <65 years) and young (≥45 years) patients. BCs in elderly individuals exhibited fewer germline but were numerically enriched in somatic homologous recombination deficiency (HRD)/DNA damage response (DDR) genetic alterations. Primary ER+/HER2- BC in elderly patients showed shifts in the spectrum of actionable PI3K/AKT alterations, whereas metastatic cases were enriched in FAT1 and RB1 mutations and fewer ESR1 mutations, suggesting age-dependent therapeutic resistance mechanisms. Metastatic ER+/HER2- lobular BCs were enriched in actionable ERBB2 mutations. Resistance-associated alterations were more prevalent in metastatic vs primary BC in elderly patients. Our findings reveal distinct actionable genetic features in elderly patients, highlighting the importance of genomic profiling and treatment personalization in this population.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"70"},"PeriodicalIF":6.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246064/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608871","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

Advancing equitable access to innovation in breast cancer. 促进乳腺癌创新的公平获取。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-10 DOI: 10.1038/s41523-025-00768-1

Seamus O'Reilly, Ines Vaz Luis, Virginie Adam, Evangelia D Razis, Ander Urruticoechea, Amal Arahmani, Eva Carrasco, Boon H Chua, Judith Bliss, Carolyn Straehle, Theodora Goulioti, Barbro Lindholm, Gustavo Werustsky, Etienne Brain, Philippe L Bedard, Giuseppe Curigliano, Sherene Loi, Shigehira Saji, David Cameron

引用次数: 0

Exploring ID4 as a driver of aggression and a therapeutic target in triple-negative breast cancer. 探索ID4作为三阴性乳腺癌侵袭性驱动因子和治疗靶点的作用。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-10 DOI: 10.1038/s41523-025-00787-y

C Toro, S Real, S Laurito, M T Branham

{"title":"Exploring ID4 as a driver of aggression and a therapeutic target in triple-negative breast cancer.","authors":"C Toro, S Real, S Laurito, M T Branham","doi":"10.1038/s41523-025-00787-y","DOIUrl":"10.1038/s41523-025-00787-y","url":null,"abstract":"Basal-like breast cancer (BLBC) is an aggressive subtype with poor prognosis and limited treatment options. The Inhibitor of Differentiation 4 (ID4) protein is frequently overexpressed in BLBC, yet its role in tumor progression remains unclear. Here, we used CRISPR-Cas9-mediated ID4 knockout, pharmacologic inhibition, in vivo xenografts, and transcriptomic analysis to investigate ID4 function. ID4 loss in MDA-MB-231 cells reduced proliferation, colony formation, Ki67 expression, and tumor growth in vivo. TCGA analysis showed improved relapse-free survival in patients with low ID4 expression. Gene set enrichment revealed a luminal-like transcriptional profile in ID4-low tumors, including increased estrogen response and inflammatory signaling. Transcription factor activity analysis indicated MYC, JUN, and STAT activation, suggesting a shift toward differentiation. The ID4 degrader AGX51 also suppressed TNBC cell proliferation. Together, these findings identify ID4 as a driver of BLBC aggressiveness and support its inhibition as a promising therapeutic strategy for improving outcomes in triple-negative breast cancer.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"69"},"PeriodicalIF":6.5,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12246117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608870","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

Radiation therapy for lobular breast cancer: opportunities and challenges for leveraging radiosensitivity. 小叶性乳腺癌的放射治疗：利用放射敏感性的机遇和挑战。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-10 DOI: 10.1038/s41523-025-00788-x

Michael R Boysen, Corey W Speers, Matthew J Sikora

引用次数: 0

NR4A3 potentials M1-like macrophage polarization to facilitate anti-tumor immune responses in breast cancer. NR4A3激活m1样巨噬细胞极化促进乳腺癌抗肿瘤免疫反应。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-07 DOI: 10.1038/s41523-025-00785-0

Yi-Yu Qian, Ning Jin, Shan-Shan Rao, Ya Wang, Xin Li, Wen Pan, Pu Huang, Si-Yuan Wang, Ping-Fei Li, Yan-Kai Lv, Qing-Lei Gao, Yu Xia

{"title":"NR4A3 potentials M1-like macrophage polarization to facilitate anti-tumor immune responses in breast cancer.","authors":"Yi-Yu Qian, Ning Jin, Shan-Shan Rao, Ya Wang, Xin Li, Wen Pan, Pu Huang, Si-Yuan Wang, Ping-Fei Li, Yan-Kai Lv, Qing-Lei Gao, Yu Xia","doi":"10.1038/s41523-025-00785-0","DOIUrl":"10.1038/s41523-025-00785-0","url":null,"abstract":"Breast cancer (BC) is commonly labeled a \"cold tumor\" due to its dense population of immunosuppressive cells, particularly M2-like macrophages, which contribute to its resistance to therapy. Thus, there is a pressing need to shift the macrophage polarization towards M1 and revitalize the tumor immune microenvironment (TIME) to improve BC prognosis. In this study, we leveraged published RNA-sequencing data and performed multiplex immunohistochemistry on clinical specimens to identify NR4A3 as a promising biomarker for favorable outcomes in BC. High NR4A3 expression correlates with an inflamed TIME, characterized by heightened T-cell infiltration and activation. NR4A3 was preferentially expressed in macrophages and fostered M1-like macrophage polarization through direct binding to p65, thereby enhancing NF-κB transcriptional activity. Overexpression of Nr4a3 in tumor-infiltrating macrophages significantly inhibited the growth of E0771 tumors in a syngeneic mouse model, accompanied by increased T-cell infiltration and elevated production of functional cytokines. Conversely, suppression of Nr4a3 in macrophages compromised T-cell recruitment and diminished their anti-tumor capabilities. Consistent with these findings, co-culture experiments involving human T cells and NR4A3-overexpressing THP1 cells further demonstrated enhanced T-cell functionality. Collectively, our findings uncover a novel role for NR4A3 in macrophage polarization and TIME remodeling, offering a potential biomarker for favorable BC prognosis and a therapeutic target to enhance immunotherapy efficacy.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"67"},"PeriodicalIF":6.5,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12234874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144584402","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

Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients. 免疫疗法治疗早期HR+乳腺癌患者的动态单细胞全身免疫反应

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-03 DOI: 10.1038/s41523-025-00776-1

Xiaopeng Sun, Margaret L Axelrod, Adrienne G Waks, Jingxin Fu, Molly DiLullo, Eliezer M Van Allen, Sara M Tolaney, Elizabeth A Mittendorf, Yaomin Xu, Justin M Balko

{"title":"Dynamic single-cell systemic immune responses in immunotherapy-treated early-stage HR+ breast cancer patients.","authors":"Xiaopeng Sun, Margaret L Axelrod, Adrienne G Waks, Jingxin Fu, Molly DiLullo, Eliezer M Van Allen, Sara M Tolaney, Elizabeth A Mittendorf, Yaomin Xu, Justin M Balko","doi":"10.1038/s41523-025-00776-1","DOIUrl":"10.1038/s41523-025-00776-1","url":null,"abstract":"The limited added benefit of immune checkpoint inhibitors in breast cancer indicates the pressing need to identify biomarkers of response to minimize risk and maximize benefit. We used single cell RNA sequencing and T cell receptor (TCR) sequencing of peripheral blood mononuclear cells (for 28 samples comprising 79,284 cells) to monitor the peripheral immune dynamic of an exploratory cohort of hormone receptor positive breast cancer patients treated with neoadjuvant nab-paclitaxel+pembrolizumab with the ultimate goal of identifying potential peripheral blood predictive biomarkers. In responsive patients, Granzyme B positive (GZMB+) cytotoxic CD8 T cells expanded post-nab-paclitaxel+pembrolizumab, accompanied by rapid changes in TCR clones. In contrast, non-responders' peripheral T cells may experience terminal exhaustion and are not significantly altered by treatment. In addition, B cell and monocyte-specific interferon response signatures were also associated with response. Our data suggests that peripheral immunological signatures may represent a facile way to monitor dynamic antitumor immune response.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"65"},"PeriodicalIF":6.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560633","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

Use of membrane lipidome, body weight, and composition in stratification of early breast cancer patients. 膜脂组、体重和成分在早期乳腺癌患者分层中的应用。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-03 DOI: 10.1038/s41523-025-00784-1

Carla Ferreri, Rosaria Ferreri, Alessio Filippone, Maria Maddalena Rossi, Cristina Rossi, Claudia Maggiore, Annalisa Di Micco, Gianluca Franceschini, Anna Sansone, Gessica Batani, Riccardo Masetti, Stefano Magno

{"title":"Use of membrane lipidome, body weight, and composition in stratification of early breast cancer patients.","authors":"Carla Ferreri, Rosaria Ferreri, Alessio Filippone, Maria Maddalena Rossi, Cristina Rossi, Claudia Maggiore, Annalisa Di Micco, Gianluca Franceschini, Anna Sansone, Gessica Batani, Riccardo Masetti, Stefano Magno","doi":"10.1038/s41523-025-00784-1","DOIUrl":"10.1038/s41523-025-00784-1","url":null,"abstract":"Fat quality and quantity have a strong impact on cancer metabolism, however, in oncology practice, only body mass index (BMI) is evaluated. The observational prospective study performed at Fondazione Policlinico Gemelli explored the combination of membrane lipidome, BMI, and body composition, together with nutritional information, as evaluation criteria of fifty newly diagnosed early breast cancer patients (BRECALIP study). The fatty acid content of red blood cell membrane phospholipids, dividing patients by the BMI, individuated normal weight subjects for their molecular signatures different from the other groups, pointing to increased membrane fluidity and inflammation (saturated fatty acid decrease, omega-6 fatty acid increase), known to sustain cancer proliferation. Fat mass (FM% ≥30) and phase angles (PA° ≥ 5.6) in the normal weight group correlated with specific pro-inflammatory fatty acid modifications. Such patient stratification, confirmed by large and longitudinal studies, can better individuate nutritional/metabolic risks of inflammatory implications in breast cancer.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"66"},"PeriodicalIF":6.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12229569/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560634","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

Regular aspirin use, breast tumor characteristics and long-term breast cancer survival. 定期服用阿司匹林，乳腺肿瘤特征和长期乳腺癌生存。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-01 DOI: 10.1038/s41523-025-00775-2

Cheng Peng, Tengteng Wang, Michelle D Holmes, Wendy Y Chen, Kristen D Brantley, Phuong Anh Le, Yujing J Heng, Pepper J Schedin, Bernard A Rosner, Walter C Willett, Meir J Stampfer, Rulla M Tamimi, A Heather Eliassen

{"title":"Regular aspirin use, breast tumor characteristics and long-term breast cancer survival.","authors":"Cheng Peng, Tengteng Wang, Michelle D Holmes, Wendy Y Chen, Kristen D Brantley, Phuong Anh Le, Yujing J Heng, Pepper J Schedin, Bernard A Rosner, Walter C Willett, Meir J Stampfer, Rulla M Tamimi, A Heather Eliassen","doi":"10.1038/s41523-025-00775-2","DOIUrl":"10.1038/s41523-025-00775-2","url":null,"abstract":"Epidemiologic data, supported by experiments, suggest aspirin may improve survival in breast cancer patients. However, recent trials reported a lack of protection, though the length of intervention was limited. Among 10,705 stages I-III breast cancer patients in the Nurses' Health Studies (NHS/NHSII), we examined the associations between post-diagnostic aspirin use and long-term breast cancer survival. During up to 34 years of follow-up, regular post-diagnostic aspirin use was associated with a 38% and 28% lower risk of breast cancer-specific and total mortality. Associations were more evident with longer duration of post-diagnostic aspirin use but attenuated with higher stage and older age at diagnosis. Pre-diagnostic long-term aspirin use was associated with the downregulation of tumor proliferation pathways in NHS/NHSII and the aspirin-gene-expression-signature predicted better survival in METABRIC. Our study highlighted the need for trials with longer duration and suggested that aspirin use before diagnosis may alter the tumor-microenvironment towards a less proliferative type.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"62"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144541596","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

Insights from a multi-institutional registry show duration of endocrine treatment for DCIS impacts second events. 来自多机构注册的见解显示DCIS的内分泌治疗持续时间影响第二事件。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-01 DOI: 10.1038/s41523-025-00774-3

Thomas J O'Keefe, Christina Yau, Emma Iaconetti, Eliza Jeong, Case Brabham, Paul Kim, Joseph McGuire, Ann Griffin, Anne M Wallace, Laura J Esserman, Olivier Harismendy, Gillian L Hirst

{"title":"Insights from a multi-institutional registry show duration of endocrine treatment for DCIS impacts second events.","authors":"Thomas J O'Keefe, Christina Yau, Emma Iaconetti, Eliza Jeong, Case Brabham, Paul Kim, Joseph McGuire, Ann Griffin, Anne M Wallace, Laura J Esserman, Olivier Harismendy, Gillian L Hirst","doi":"10.1038/s41523-025-00774-3","DOIUrl":"10.1038/s41523-025-00774-3","url":null,"abstract":"Ductal carcinoma in situ (DCIS) incidence has risen rapidly with the introduction of screening mammography, yet it is unclear who benefits from both the amount and type of adjuvant treatment (radiation therapy, endocrine therapy) versus what constitutes over-treatment. Our goal was to identify the effects of adjuvant radiation therapy, or endocrine ± radiation therapy versus breast conservation surgery alone in a large multi-center registry of retrospective DCIS cases (N = 1916) with median follow up of 7.0 (IQR: 8.43) years. We show that patients with DCIS who took less than 2 years of adjuvant endocrine therapy alone have a similar second event rate as breast conservation surgery. However, patients who took more than 2 years of endocrine therapy show a significantly reduced second event rate, similar to those who received either radiation or combined endocrine + radiation therapy, which was independent of age, tumor size, grade, or period of diagnosis. This highlights the importance of endocrine therapy duration for risk reduction.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"63"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12216362/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144541573","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

Quantitative analysis of T cell subsets in a population of Black women with invasive breast cancer. 浸润性乳腺癌黑人妇女群体中T细胞亚群的定量分析。

IF 6.5 2区医学

NPJ Breast Cancer Pub Date : 2025-07-01 DOI: 10.1038/s41523-025-00780-5

Angela R Omilian, Lucas Mendicino, Anthony George, Tina Darabnoushtehrani, Rochelle Payne Ondracek, Wiam Bshara, Chi-Chen Hong, Bo Qin, Elisa V Bandera, Thaer Khoury, Rikki Cannioto, Song Yao, Christine B Ambrosone

{"title":"Quantitative analysis of T cell subsets in a population of Black women with invasive breast cancer.","authors":"Angela R Omilian, Lucas Mendicino, Anthony George, Tina Darabnoushtehrani, Rochelle Payne Ondracek, Wiam Bshara, Chi-Chen Hong, Bo Qin, Elisa V Bandera, Thaer Khoury, Rikki Cannioto, Song Yao, Christine B Ambrosone","doi":"10.1038/s41523-025-00780-5","DOIUrl":"10.1038/s41523-025-00780-5","url":null,"abstract":"We compared T cell subpopulations in primary invasive breast tumors from Black and White women and investigated breast cancer subtype-specific associations of T cell abundance with survival in Black women. Multispectral immune staining was used to quantify helper, cytotoxic, and regulatory T cells in the tumor and stromal compartments of breast tissues. In fully adjusted models, breast tumors from Black women were significantly more likely than those from White women to have a higher abundance of cytotoxic T cells (IRR, 2.41; 95% CI, 1.43-4.05) and helper T cells (IRR, 1.80; 95% CI, 1.06-3.06), and these differences were more pronounced in the tumor than the stromal compartment. Among Black women, higher levels of T cells were associated with improved survival in women with triple-negative breast cancer, whereas a trend of poorer survival was observed in women with HER2-positive tumors. This study contributes to an accumulating body of evidence that the tumor-immune landscape differs between Black and White women.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":"11 1","pages":"64"},"PeriodicalIF":6.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12218130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144541574","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