NPJ Breast Cancer最新文献

{"title":"Platinum-based neoadjuvant chemotherapy and the predictive role of DNA damage response biomarkers in TNBC: the NeoCarbo study.","authors":"Eriseld Krasniqi, Anna Di Benedetto, Lorena Filomeno, Teresa Arcuri, Cristiana Ercolani, Gianluigi Ferretti, Simona Gasparro, Alberto Fulvi, Arianna Roselli, Loretta D'Onofrio, Laura Pizzuti, Maddalena Barba, Marcello Maugeri-Saccà, Claudio Botti, Franco Graziano, Ilaria Puccica, Sonia Cappelli, Fabio Pelle, Flavia Cavicchi, Amedeo Villanucci, Ida Paris, Tatiana D'Angelo, Fabio Calabrò, Sandra Rea, Roy De Vita, Letizia Perracchio, Giuseppe Sanguineti, Silvia Takanen, Laura Marucci, Lucia Goanta, Laura Greco, Ramy Kayal, Pina Tiziana Falbo, Paola Scavina, Matteo Vergati, Marco Mazzotta, Nicola Calonaci, Mauro Minelli, Giuliana D'Auria, Giulio Caravagna, Giovanni Blandino, Patrizia Vici","doi":"10.1038/s41523-026-00977-2","DOIUrl":"10.1038/s41523-026-00977-2","url":null,"abstract":"<p><p>Platinum-containing neoadjuvant chemotherapy increases pathological complete response (pCR) rates in triple-negative breast cancer (TNBC), but predictive biomarkers remain incompletely defined. In the multicenter NeoCarbo cohort, we assessed a carboplatin-containing neoadjuvant regimen and examined whether germline homologous recombination deficiency (HRD) and baseline tumor DNA damage response (DDR) activation predict pCR and outcomes. Stage I-III TNBC patients at three centers received carboplatin (AUC6 q3w×4) plus weekly paclitaxel (×12), followed by dose-dense epirubicin/cyclophosphamide (q2w×4) and surgery. The primary endpoint was pCR (ypT0/is ypN0); secondary endpoints were disease-free survival (DFS) and overall survival (OS). Germline HRD was defined by pathogenic/likely pathogenic variants in BRCA1/2 and other homologous recombination genes, and DDR activation was assessed centrally by phospho-DDR immunohistochemistry. Among 128 patients, pCR occurred in 77 (60.2%; 95% CI 51.1-68.7%). HRD status was available in 80 patients (28 HRD-positive), with pCR rates of 78.6% in HRD-positive versus 57.7% in HRD-negative tumors (Fisher p = 0.086). In a bivariable analysis restricted to patients with complete biomarker data, HRD positivity independently predicted pCR (adjusted OR 2.68; 95% CI 1.16-6.85; p = 0.027), whereas DDR tertiles were not independently associated with pCR. At a median follow-up of 60.4 months, pCR was associated with improved DFS (HR 0.29; 95% CI 0.12-0.72; p = 0.008) and OS (HR 0.30; 95% CI 0.12-0.81; p = 0.017). Grade ≥3 toxicity occurred in 14.4% during carboplatin-paclitaxel and 18.9% during epirubicin-cyclophosphamide, predominantly hematologic. These findings support high pCR rates with this regimen and suggest that HRD may identify patients more likely to achieve pCR, whereas baseline tumor phospho-DDR lacked predictive value; future evaluation may require dynamic DDR assessment in larger studies.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055874","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":"Preoperative onapristone-XR in postmenopausal women with progesterone receptor-positive (PgR+)/HER2-negative early breast cancer: SOLTI-1802 ONAWA trial results.","authors":"Meritxell Bellet, Juan M Ferrero-Cafiero, Milana Bergamino Sirvén, Claudette Falato, Xavier González, Kepa Amillano, Nuria Chic, Serafin Morales, Ariadna Gasol, Paolo Nuciforo, Guillermo Villacampa, Patricia Villagrasa, Caroline H Diep, Davis Seelig, Carol Lange, Antonio D'Assoro, Aleix Prat, Tomás Pascual, Cristina Saura","doi":"10.1038/s41523-025-00887-9","DOIUrl":"10.1038/s41523-025-00887-9","url":null,"abstract":"<p><p>Onapristone, a type-1 antiprogestin, has been tested for advanced breast cancer (BC), but its activity in early-stage, hormone receptor-positive, HER2-negative BC has not been fully explored. The ONAWA trial (ClinicalTrials.gov ID: NCT04142892- Registered on January 6, 2021) was a single-arm study evaluating the preoperative effects of onapristone with extended-release formulation (ONA-XR) (50 mg BID for 21 days) in postmenopausal women with Progesterone Receptor-positive (PgR+)/HER2-negative early BC. No complete cell cycle arrest (CCCA) was achieved at day 21, however ONA-XR significantly suppressed tumor proliferation with a Ki-67 geometric mean change of -17.78% (CI95 -39.76% to 12.20%) particularly in tumors with baseline PgR≥90% (-46.21%; CI -63.02% to -21.76%). Immunohistochemistry showed suppression of phospho-Ser294-PgR and p-STAT3, indicating effects on proliferation and endocrine pathways. Treatment also induced a shift to a more endocrine-sensitive phenotype. Of the 10 patients, 60% experienced adverse events, including one grade 3 increase in gamma-glutamyltransferase. In conclusion, ONA-XR showed early tumor proliferation suppression, particularly in high PgR-expressing tumors, supporting its potential for further clinical evaluation.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055902","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":"Potential treatment targets in the whole-tissue proteome of triple negative breast cancer.","authors":"Tram B Doan, Merridee A Wouters, Jiashu Hu, Jennifer M S Koh, Erin K Sykes, Clare Loudon, Zainab Noor, Nirmala Pathmanathan, Jane E Armes, Peter G Hains, Phillip J Robinson, Qing Zhong, Roger R Reddel, J Dinny Graham, Rosemary L Balleine","doi":"10.1038/s41523-026-00976-3","DOIUrl":"https://doi.org/10.1038/s41523-026-00976-3","url":null,"abstract":"<p><p>Triple Negative Breast Cancer (TNBC) is recognised as heterogeneous, with distinct subtypes specified by histopathologic and gene expression analysis. However, these do not align closely to treatment response and there is an on-going need for both clinically applicable biomarkers and new effective treatments. Comprehensive profiling of the TNBC tissue proteome has potential to bring new perspective to these challenges. We report global proteomic profiles of 312 TNBC cases derived from Data Independent Acquisition-Mass Spectrometry (DIA-MS) analysis, coupled with gene expression profiling in a subset of cases (n = 97). This showed differential expression of protein cassettes reflecting the key features of 1) cellular growth and proliferation, 2) immune activation, 3) mesenchymal elements and 4) luminal androgen receptor phenotype. In combination, these cassettes distinguished TNBC subtypes that align to potential treatments. We also found an association between immune activation and improved survival that was influenced by the presence of lymph node metastases. In our cohort and in a validation dataset, the combination of a five protein immune activation signature with lymph node status was highly predictive of survival, suggesting that a combination of tissue proteomics with clinical features could be an informative guide to TNBC management. This large proteomic study forms a resource to progress this goal.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148055885","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}

{"title":"Risk factors for second primary cancer in patients who survive breast cancer.","authors":"Phillip Park, Keunkyun Kim, Dong-Woo Choi, Heejung Chae, So-Youn Jung, Hyun-Jin Kim","doi":"10.1038/s41523-026-00975-4","DOIUrl":"10.1038/s41523-026-00975-4","url":null,"abstract":"<p><p>Breast cancer survivors are living longer. However, the risk of second primary cancer (SPC) remains a concern. The aim of this study was to identify risk factors for synchronous SPC (sSPC) and metachronous SPC (mSPC) among patients who survive breast cancer and evaluate causes of death. This population-based cohort study used data from the South Korean Cancer Public Library Database, which integrates the national cancer registry with insurance claim and health screening data. Female patients diagnosed with primary breast cancer between 2012 and 2019 were included in the study. SPCs were defined as new histologically distinct malignancies occurring six months or more (mSPC) or less than six months (sSPC) after breast cancer diagnosis. Cox proportional hazards models were used to identify risk factors for SPC. Cumulative incidence and causes of death were examined by cancer stage and age. Among 15,430 women with breast cancer who met the eligibility criteria, 497 developed sSPC and 812 developed mSPC. In multivariable models, an age ≥70 vs <40 years was associated with a higher risk of both sSPC (hazard ratio [HR], 3.58; 95% confidence interval [CI], 2.01-6.36; P < 0.001) and mSPC (HR, 3.18; 95% CI, 2.06-4.91; P < 0.001). Fasting blood sugar ≥140 mg/dL was associated with sSPC (HR, 1.61; 95% CI, 1.06-2.45; P = 0.02), but not with mSPC. Cumulative-incidence curves showed a higher prevalence of thoracic and gastrointestinal mSPC in older and lower-income strata, consistent with Cox results. Although smoking was more prevalent in low-income groups, it was not an independent predictor. Cause-of-death analyses indicated that SPCs more often accounted for death in older survivors and in those with early-stage index breast cancer. The results of this study identify metabolic and socioeconomic factors as key predictors of SPC in patients who survive breast cancer. Tailored survivorship strategies are needed for high-risk subgroups, including older patients and those with low incomes or poor metabolic profiles.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13493786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148042918","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":"WISDOM randomized trial comparing risk-based versus annual breast cancer screening: study cohort characteristics and design.","authors":"Allison Fiscalini, Kelly Blum, Kirkpatrick Fergus, Robert A Hiatt, Arash Naeim, Andrea Kaster, Maren T Scheuner, Laura J van 't Veer, Andrea Z LaCroix, Alexander D Borowsky, Olufunmilayo I Olopade, Hannah L Park, James Esserman, Rachael Lancaster, Diane Heditsian, Susie Brain, Vivian Lee, Deborah L Goodman, Katherine S Ross, Neil Wenger, Barbara A Parker, Lisa Madlensky, Jeffrey A Tice, Yiwey Shieh, Elad Ziv, Vignesh A Arasu, Hoda Anton-Culver, Celia P Kaplan, Kim F Rhoads, Kimberly Badal, Michael Hogarth, Antonia Petruse, Irene A Soto, Katherine Leggat-Barr, Steffanie Goodman, Jennifer Atamer, Rita Ryu, Kelly Adduci, Jeffrey B Matthews, Martin Eklund, Leah P Sabacan, Laura Esserman","doi":"10.1038/s41523-026-00952-x","DOIUrl":"10.1038/s41523-026-00952-x","url":null,"abstract":"<p><p>The Women Informed to Screen Depending on Measures of risk (WISDOM) Study (clinicaltrials.gov NCT02620852, 2016-08-31) is pragmatic randomized controlled trial evaluating risk assessment to inform the age to start, frequency and modality of breast cancer screening and risk reduction. The WISDOM Study uses a preference-tolerant design, enabling women who decline randomization to self-select their screening arm. The risk-based arm included comprehensive breast cancer risk assessment using the Breast Cancer Surveillance Consortium (BCSC) model and genetics. From August 2016 to February 2023, WISDOM enrolled a large, diverse, nationwide cohort of 46,403 participants - 77% non-Hispanic (NH) White, 9% Hispanic, 6% (NH) Black, and 5% (NH) Asian; demographic diversity increased over time. Mean age at baseline was 54 years. 28,372 (61%) were randomized, while 89% of those who self-selected their screening arm chose risk-based screening. The preference-tolerant design captured real-world screening preferences while maintaining scientific rigor and demonstrated strong preference for risk-based screening.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13478457/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005935","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":"USP7 inhibition perturbs proteostasis and tumorigenesis in triple-negative breast cancer.","authors":"Ahhyun Kim, Priya Gopalakrishnan, Marina Suárez-Pizarro, Claire C Chen, Xianxi Wang, Sydney M McCoy, Nikita Umesh, Angie Mordant, Natalie K Barker, Laura E Herring, Rasha T Kakati, Philip M Spanheimer, Michael J Emanuele, Claudia A Benavente","doi":"10.1038/s41523-026-00974-5","DOIUrl":"10.1038/s41523-026-00974-5","url":null,"abstract":"<p><p>The deubiquitinase USP7 is a critical regulator of tumorigenesis, known for stabilizing the MDM2-p53 pathway. Emerging evidence highlights USP7's p53-independent roles in proliferation and tumorigenesis. Our study reveals that USP7 is broadly upregulated in breast cancer, including triple-negative breast cancer (TNBC), a subtype characterized by near-universal TP53 loss. This provides a model to investigate p53-independent functions of USP7. Using TNBC models, we define p53-independent roles of USP7 in regulating proteostasis and tumorigenesis. Importantly, genetic and pharmacologic USP7 inactivation impaired tumor progression in TNBC models. To explore USP7's role in p53-mutant TNBCs, we performed deep quantitative proteomics across TNBC cell lines, identifying shared USP7 targets involved in cell proliferation, genome stability, and proteostasis. Acute USP7 inactivation allowed us to infer proximally controlled proteins that are likely direct targets. Surprisingly, many of the proteins downregulated by USP7 inhibition are E3 ubiquitin ligases. Thus, a key USP7 function in TNBC is to antagonize the degradation of ubiquitinating enzymes, since these enzymes are often susceptible to auto-ubiquitination and degradation. Notably, we identified TOPORS, a dual ubiquitin- and SUMO-ligase, among novel USP7 substrates. TOPORS interacts with the BRCA1-A DNA damage repair complex, suggesting a USP7-TOPORS-BRCA1-A axis that might further explain the continued proliferation of genomically unstable TNBCs. Collectively, these data nominate USP7 as a potential therapeutic vulnerability in TNBC.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13473141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005979","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":"Women's preferences for breast cancer risk-reducing medications: a discrete choice experiment study.","authors":"Qi Gao, Si Ning Serene Goh, Alexis Jiaying Khng, Mikael Hartman, Yi Wang, Jingmei Li","doi":"10.1038/s41523-026-00972-7","DOIUrl":"10.1038/s41523-026-00972-7","url":null,"abstract":"<p><p>Despite strong evidence that chemoprevention reduces breast cancer risk in high-risk women, uptake remains low. We hypothesized that healthy women evaluate preventive medications differently from patients and that understanding delivery preferences may inform more acceptable strategies. We conducted a discrete choice experiment with eight attributes: reduction in lifetime breast cancer risk by age 70, treatment duration, modality, frequency, medical recommendation, fertility impact, side effects, and total cost. Women aged 21-59 without prior breast cancer were recruited in Singapore. Each participant completed choice tasks under two perceived lifetime risk scenarios (30% and 80%). Preferences were analyzed using mixed logit models, with conditional relative importance and marginal willingness-to-pay estimated. Among 618 women, respondents generally preferred risk-reducing treatment over no treatment. Across risk scenarios, shorter duration, minimal fertility impact, and fewer side effects were consistently valued. Cost strongly influenced choices, although less so at higher baseline risk. Cost and side effects were the most important attributes in both scenarios. Willingness-to-pay estimates indicated strong aversion to severe side effects and long durations, and a preference for specialist over general practitioner recommendations. Preferences varied by sociodemographic and clinical characteristics. No significant preference differences were observed across delivery modalities.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13463033/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988384","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":"Ultra-high tumor mutation burden breast cancer: genomic profiling and real-world immunotherapy results.","authors":"Kristina Fanucci, Mariya Rozenblit, Julia C F Quintanilha, Ryon P Graf, Neal Fischbach, Maureen Pelletier, Abirami Sivapiragasam, Prashanth Ashok Kumar, Mansi Kallem, Ethan S Sokol, Smruthy Sivakumar, Dean C Pavlick, Jeffrey S Ross, Maryam Lustberg, Lajos Pusztai","doi":"10.1038/s41523-026-00965-6","DOIUrl":"10.1038/s41523-026-00965-6","url":null,"abstract":"<p><p>Patients with metastatic breast cancer and tumor mutational burden (TMB) ≥10 mutations/megabase are eligible for immunotherapy, but clinical and genomic characteristics and outcomes of patients with ultra-high TMB (UHTMB) ≥20 mutations/megabase remain under-characterized. In this retrospective cohort and comparative effectiveness study we examined comprehensive genomic profiling assessed on tumors as part of routine care. Real-world time to next treatment (TTNT), and overall survival (rwOS) data were collected from the Flatiron Database. 45/2049 (2.2%) patients had UHTMB; patients with UHTMB were more likely to have estrogen receptor-positive disease (86.6% vs. 70.0%), lobular histology (40.0% vs. 14.5%), and PIK3CA mutation (81.8% vs. 37.9%) vs. patients with TMB ≤ 20. Patients with UHTMB who received immunotherapy had longer TTNT (4.9 vs. 2.6 months, hazard ratio (HR) = 0.49, 95% confidence interval (CI):0.26-0.91,p = 0.025) and longer rwOS (14.1 vs. 3.2 months, HR = 0.37, 95%CI:0.18-0.76,p = 0.007) than patients with TMB <10. Single agent immunotherapy is an important treatment option for patients with UHTMB.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13462879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981986","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":"Dual ctDNA and CTCs analysis for minimal residual disease detection and relapse monitoring in early-stage breast cancer.","authors":"Jesús Velasco-Suelto, María Elena Quirós-Ortega, Javier Pascual, Ana Godoy-Ortiz, Alfonso Alba-Bernal, Esperanza López-López, María Emilia Domínguez-Recio, Begoña Jiménez-Rodríguez, Jesús Peralta-Linero, Estefanía Bellagarza-García, Laura Troyano-Ramos, Guadalupe Garrido-Ruiz, M Isabel Hierro-Martín, María Victoria Ortega, Alicia Garrido-Aranda, Rocío Lavado-Valenzuela, Martina Álvarez, Emilio Alba, Iñaki Comino-Méndez","doi":"10.1038/s41523-026-00970-9","DOIUrl":"10.1038/s41523-026-00970-9","url":null,"abstract":"<p><p>Early detection of minimal residual disease (MRD) by liquid biopsy could enable earlier relapse identification in early-stage breast cancer (BC), but most approaches are single-analyte. We prospectively studied 58 patients with early-stage BC, including HR+/HER2-, triple-negative, and HER2+ subtypes, treated with neoadjuvant chemotherapy or primary surgery plus adjuvant therapy. Patient-specific droplet digital PCR assays were designed for both ctDNA and CTCs analysis, with one truncal tumour mutation tracked per patient for detection in both analytes, in serial high-volume blood samples collected at diagnosis before treatment, approximately 1 month after surgery, and at 6-month intervals during follow-up in patients at high risk of relapse. We developed a composite Liquid biopsy Minimal Residual Disease (L-MRD) score integrating six clinical and molecular variables. At baseline (pre-treatment), ctDNA and/or CTCs were detected in 67.2% of patients and remained positive post-surgery in 53.6%. During follow-up, MRD detection anticipated all relapses (100% sensitivity; median lead time 27.95 months) and the L-MRD score stratified 5-year recurrence risk (2.2% vs 41.6%; HR = 6.6; P = 0.04) with strong performance (AUC = 0.891; NPV = 97.8%). This dual-analyte, longitudinal MRD strategy improves relapse prediction and supports further research regarding the clinical utility of personalised surveillance in early-stage BC.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575130/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147982707","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":"Targeting microRNA let-7b-5p-mediated aberrant androgen receptor signaling for prevention of hormone receptor-negative breast cancer.","authors":"Leslie Faye Cando, Janvi Sandhu, Zhenlin Ju, Constance T Albarracin, Leslie Michelle Dalmacio, Jing Wang, Anjana Bhardwaj, Isabelle Bedrosian","doi":"10.1038/s41523-026-00938-9","DOIUrl":"10.1038/s41523-026-00938-9","url":null,"abstract":"<p><p>Androgen receptor, the key mediator of the AR signaling pathway, is expressed in the majority of breast cancers and has been emerging as a potential target for treatment with encouraging results in preclinical and clinical trials. But whether AR plays a role in the preneoplastic context to serve as a target for breast cancer prevention is unknown. Our results showed upregulation of AR expression in the preneoplastic and preinvasive sublines of the MCF10A breast cancer progression model. Similarly, we observed a trend towards higher expression of AR in the tumors and matched histologically normal mammary tissues of TNBC-LAR patients compared to normal noncancer controls. Mechanistically, we identified AR as a novel gene target of tumor suppressor microRNA let-7b-5p, which directly binds the AR 3' untranslated region. Mirroring AR upregulation, there was a corresponding loss of let-7b-5p expression in tumors of TNBC patients. By targeting this aberrant let-7b-5p-mediated AR signaling pathway with AR inhibitor enzalutamide, the growth and survival of preneoplastic and preinvasive lesions were significantly reduced in cell line models. Overall, our study highlights the role of let-7b-5p-mediated aberrant AR signaling in breast tumorigenesis and as a potential target for prevention in populations at risk for hormone receptor-negative breast cancer.</p>","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147981558","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}