NPJ Breast Cancer最新文献_第7页

Positron-emission tomography as a predictor of response to first-line cyclin-dependent kinase 4/6 inhibitors in patients with metastatic ER-positive HER2-negative breast cancer. 正电子发射断层扫描作为转移性er阳性her2阴性乳腺癌患者对一线细胞周期蛋白依赖性激酶4/6抑制剂反应的预测因子

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-05-11 DOI: 10.1038/s41523-026-00962-9

Marcin Kubeczko, Anna Polakiewicz-Gilowska, Andrea d'Amico, Olgierd Chrabański, Katarzyna Świderska, Ewa Chmielik, Barbara Bobek-Billewicz, Daria Handkiewicz-Junak, Michał Jarząb

{"title":"Positron-emission tomography as a predictor of response to first-line cyclin-dependent kinase 4/6 inhibitors in patients with metastatic ER-positive HER2-negative breast cancer.","authors":"Marcin Kubeczko, Anna Polakiewicz-Gilowska, Andrea d'Amico, Olgierd Chrabański, Katarzyna Świderska, Ewa Chmielik, Barbara Bobek-Billewicz, Daria Handkiewicz-Junak, Michał Jarząb","doi":"10.1038/s41523-026-00962-9","DOIUrl":"10.1038/s41523-026-00962-9","url":null,"abstract":"Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) are the standard first-line treatment for metastatic estrogen receptor-positive, HER2-negative breast cancer, yet acquired resistance remains a major challenge. Reliable biomarkers for prognostic stratification are therefore needed. We retrospectively analyzed 174 patients treated with first-line CDK4/6i between 2018 and 2023 who underwent baseline 18F-fluorodeoxyglucose positron emission tomography. Associations between baseline SUVmax and clinical outcomes were assessed using Kaplan-Meier estimates, Cox proportional hazards models, logistic regression for early progression, and receiver-operating characteristic (ROC) analysis for cut-off determination. Higher SUVmax was significantly associated with shorter progression-free survival (PFS; HR 1.11, 95% CI 1.05-1.16, p < 0.001) and overall survival (OS; HR 1.10, 95% CI 1.02-1.18, p = 0.016). Patients with SUVmax <8.0 experienced markedly longer PFS and improved 2-year PFS compared with those with SUVmax ≥8.0. Similarly, 2-year OS was substantially higher among patients with lower SUVmax values. In multivariable analysis, SUVmax remained an independent prognostic factor for PFS. Higher SUVmax was also associated with early progression, with an 18% increase in odds per unit (OR 1.18, 95% CI 1.05-1.33). These findings demonstrate that baseline SUVmax is a strong and readily accessible prognostic biomarker in patients receiving CDK4/6i, helping to identify individuals at elevated risk of early disease progression. Prospective validation is warranted.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147869053","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

Risk factors and metastatic sites in HER2-positive breast cancer with pathological complete response. 病理完全缓解的her2阳性乳腺癌的危险因素和转移部位

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-05-09 DOI: 10.1038/s41523-026-00959-4

Mayako Terao, Hiraku Kumamaru, Naoko Kinukawa, Toru Hanamura, Yasuaki Sagara, Takayuki Iwamoto, Minoru Miyashita, Takanori Ishida, Naruto Taira, Shigehira Saji, Naoki Niikura

{"title":"Risk factors and metastatic sites in HER2-positive breast cancer with pathological complete response.","authors":"Mayako Terao, Hiraku Kumamaru, Naoko Kinukawa, Toru Hanamura, Yasuaki Sagara, Takayuki Iwamoto, Minoru Miyashita, Takanori Ishida, Naruto Taira, Shigehira Saji, Naoki Niikura","doi":"10.1038/s41523-026-00959-4","DOIUrl":"10.1038/s41523-026-00959-4","url":null,"abstract":"A pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with favorable outcomes in patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer; however, brain metastases still occur. Using the National Clinical Database-Breast Cancer Registry (JAPAN 2008-2020), we identified 21,494 patients who received NAC followed by surgery. After excluding cases without pCR status or prognostic data, 8421 patients were analyzed (2430 pCR; 5991 non-pCR). Disease-free survival (DFS), brain metastasis-free survival, and recurrence patterns were compared, and risk factors for distant recurrence were evaluated. Patients achieving pCR had significantly better 5-year DFS than non-pCR patients. Among pCR cases, hormone receptor status and clinical stage independently predicted recurrence. At 5 years, brain metastases occurred in 2.6% of pCR patients and 4.5% of non-pCR patients. These findings indicate that pCR does not eliminate the risk of brain metastases, highlighting the need for continued vigilance.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13376903/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864368","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

Enabling DCIS subtyping: leveraging foundation models for robust grading and molecular biomarker scoring. 启用DCIS亚型：利用基础模型进行稳健的分级和分子生物标志物评分。

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-05-06 DOI: 10.1038/s41523-026-00957-6

S Doyle, M A Oerlemans, J Brunekreef, E Marcus, L Mulder, Y Liu, I Bouybayoune, E J Sawyer, A M Thompson, S E Pinder, Jelle Wesseling, Alastair Thompson, Serena Nik-Zainal, Elinor J Sawyer, Helen Davies, Andrew Futreal, Nicholas Navin, E Shelley Hwang, Jos Jonkers, Jacco van Rheenen, Fariba Behbod, Esther H Lips, Marjanka Schmidt, Lodewyk F A Wessels, Daniel Rea, Proteeti Bhattacharjee, Hilary Stobart, Deborah Collyar, Donna Pinto, Ellen Verschuur, Marja van Oirsouw, C I Sánchez, J Teuwen, J Wesseling, E H Lips

{"title":"Enabling DCIS subtyping: leveraging foundation models for robust grading and molecular biomarker scoring.","authors":"S Doyle, M A Oerlemans, J Brunekreef, E Marcus, L Mulder, Y Liu, I Bouybayoune, E J Sawyer, A M Thompson, S E Pinder, Jelle Wesseling, Alastair Thompson, Serena Nik-Zainal, Elinor J Sawyer, Helen Davies, Andrew Futreal, Nicholas Navin, E Shelley Hwang, Jos Jonkers, Jacco van Rheenen, Fariba Behbod, Esther H Lips, Marjanka Schmidt, Lodewyk F A Wessels, Daniel Rea, Proteeti Bhattacharjee, Hilary Stobart, Deborah Collyar, Donna Pinto, Ellen Verschuur, Marja van Oirsouw, C I Sánchez, J Teuwen, J Wesseling, E H Lips","doi":"10.1038/s41523-026-00957-6","DOIUrl":"10.1038/s41523-026-00957-6","url":null,"abstract":"Ductal Carcinoma In Situ (DCIS) is a non-obligate precursor of invasive breast cancer. Due to a lack of reliable prognostic markers, nearly all women with DCIS undergo intensive treatment-often unnecessarily. The LORD trial addresses this by offering active surveillance to women with screen-detected, ER-positive, HER2-negative, grade 1 or 2 DCIS, aiming to reduce overtreatment. To support this, we developed a deep learning pipeline based on foundation models to predict grade, ER, and HER2 status directly from H&E-stained digitized pathology slides. Models were trained and tested on a Dutch multicenter dataset (n = 887) and externally validated on a UK dataset (n = 259). On the Dutch data, the models achieved mean AUROCs of 0.90 (ER), 0.84 (HER2), and 0.86 (grade); external validation yielded 0.80, 0.74, and 0.75, respectively. Using these outputs, we stratified patients according to active surveillance criteria, reaching balanced accuracies of 0.81 (Dutch) and 0.64 (UK), with corresponding NPVs of 0.86 and 0.76. Our models generalize across cohorts and reliably predict key biomarkers, supporting the identification of DCIS patients eligible for less aggressive management.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623920/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840776","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

Co-occurring rare germline DNA repair gene variants in BRCA1/BRCA2 implicated hereditary breast cancer families. BRCA1/BRCA2中共同发生的罕见种系DNA修复基因变异与遗传性乳腺癌家族有关。

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-05-05 DOI: 10.1038/s41523-026-00956-7

Wejdan M Alenezi, Neil Recio, Caitlin T Fierheller, Corinne Serruya, Timothée Revil, Anne-Marie Mes-Masson, Diane Provencher, Celia M T Greenwood, Jiannis Ragoussis, Patricia N Tonin

{"title":"Co-occurring rare germline DNA repair gene variants in BRCA1/BRCA2 implicated hereditary breast cancer families.","authors":"Wejdan M Alenezi, Neil Recio, Caitlin T Fierheller, Corinne Serruya, Timothée Revil, Anne-Marie Mes-Masson, Diane Provencher, Celia M T Greenwood, Jiannis Ragoussis, Patricia N Tonin","doi":"10.1038/s41523-026-00956-7","DOIUrl":"10.1038/s41523-026-00956-7","url":null,"abstract":"As gene-panels expand to include candidate breast cancer predisposing genes (CPGs) involved in diverse DNA repair pathways, we investigated an index breast cancer (BC) case from 56 BRCA1/BRCA2 implicated high-risk hereditary BC families using gene-based approach for co-occurring, rare germline variants predicted to be damaging and clinically relevant in 276 DNA repair genes (DRGs). Using whole exome sequencing analyses, we identified a total of 287 variants in 55% of DRGs, of which 24 loss-of-function and 36 other predicted damaging variants were identified in 72% and 76% of BRCA1 and BRCA2 implicated cases, respectively. We also identified 60 variants of clinical interest in various known CPGs, including those involved in risk to other cancers, in 72% of BRCA1 and 60% of BRCA2 cases. The number of variants predicted to be deleterious in diverse DRGs raises questions about the interpretability of findings as panel testing expands beyond clinically established breast CPGs.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13350704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147840750","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

Imlunestrant with or without abemaciclib in advanced breast cancer: safety analyses from the EMBER-3 trial. abemaciclib治疗晚期乳腺癌：EMBER-3试验的安全性分析

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-04-27 DOI: 10.1038/s41523-026-00950-z

Joyce O'Shaughnessy, Francois-Clement Bidard, Patrick Neven, Monica Lis Casalnuovo, Philippe Aftimos, Cristina Saura, Nadia Harbeck, Lisa A Carey, Giuseppe Curigliano, Jose A Garcia-Saenz, Maria Fernandez Abad, Larissa de Paula, Yeon Hee Park, Ozgur Ozyilkan, Maria Munoz, Emily Barrett, Shanshan Cao, Aarti Chawla, Komal L Jhaveri

{"title":"Imlunestrant with or without abemaciclib in advanced breast cancer: safety analyses from the EMBER-3 trial.","authors":"Joyce O'Shaughnessy, Francois-Clement Bidard, Patrick Neven, Monica Lis Casalnuovo, Philippe Aftimos, Cristina Saura, Nadia Harbeck, Lisa A Carey, Giuseppe Curigliano, Jose A Garcia-Saenz, Maria Fernandez Abad, Larissa de Paula, Yeon Hee Park, Ozgur Ozyilkan, Maria Munoz, Emily Barrett, Shanshan Cao, Aarti Chawla, Komal L Jhaveri","doi":"10.1038/s41523-026-00950-z","DOIUrl":"10.1038/s41523-026-00950-z","url":null,"abstract":"In EMBER-3 (NCT04975308), among patients with ER + , HER2- advanced breast cancer (ABC) with recurrence/progression on/after endocrine therapy (ET), imlunestrant significantly prolonged PFS versus standard ET in patients with ESR1 mutations, and imlunestrant + abemaciclib prolonged PFS versus imlunestrant in the overall population. We report the incidence, severity, timing, and management of common treatment-emergent adverse events (TEAEs), including safety profiles of select subgroups. In both imlunestrant-containing arms, the most common TEAEs were reversible, low grade, single occurrences; occurred early in treatment; and resulted in few treatment discontinuations (imlunestrant, 5%; imlunestrant + abemaciclib, 6%). TEAEs in imlunestrant+abemaciclib arm were managed with dose adjustments (61%) and supportive medication. Imlunestrant monotherapy had a similar safety profile between patients aged <65 and ≥65 years, while imlunestrant + abemaciclib had a similar safety profile to other abemaciclib+ET combinations in both age groups. Imlunestrant and imlunestrant + abemaciclib provide effective, convenient oral therapy with a favorable and manageable safety profile for patients with ER+, HER2- ABC with recurrence/progression on/after ET.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13324159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777237","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

Multimodal analysis of a rare BARD1 missense variant suggests its pathogenicity is conditional. 一种罕见的BARD1错义变异的多模态分析表明其致病性是有条件的。

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-04-21 DOI: 10.1038/s41523-026-00955-8

Fiona Chan-Pak-Choon, Yuandi Gao, José Camacho-Valenzuela, Júlia-Jié Cabré-Romans, Amisha Minju-Op, Lili Fu, Paz Polak, Barbara Rivera, Raquel Cuella-Martin, William D Foulkes

{"title":"Multimodal analysis of a rare BARD1 missense variant suggests its pathogenicity is conditional.","authors":"Fiona Chan-Pak-Choon, Yuandi Gao, José Camacho-Valenzuela, Júlia-Jié Cabré-Romans, Amisha Minju-Op, Lili Fu, Paz Polak, Barbara Rivera, Raquel Cuella-Martin, William D Foulkes","doi":"10.1038/s41523-026-00955-8","DOIUrl":"10.1038/s41523-026-00955-8","url":null,"abstract":"Hereditary breast cancer involves multiple risk genes, including BARD1, which confers low to moderate risk and is associated with triple-negative breast cancer (TNBC). We report a proband with a primary ER+/PR+/HER2- breast cancer, which recurred unilaterally as a TNBC and who later developed endometrial cancer. Clinical germline testing revealed a rare BARD1 missense variant of uncertain significance [c.2258G>T; p.(Gly753Val)]. Whole-exome sequencing of tumors and blood revealed BARD1 loss of heterozygosity and mutational signature 3 - indicative of homologous recombination (HR) repair deficiency - exclusively in the TNBC recurrence. Functional assays demonstrated impaired HR repair via increased PARP inhibitor sensitivity and reduced RAD51 foci formation. We hypothesize that the selective pressure exerted by tamoxifen resulted in breast cancer subtype switching and uncovered the pathogenic potential of the BARD1 p.(Gly753Val) variant. This case illustrates a previously unreported scenario where the pathogenicity of a germline BARD1 variant appears conditional on prior treatment.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13284403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777158","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

Development and internal validation of mammography feature-based prognostic models for distant recurrence-free survival of invasive breast cancer in a screening cohort. 基于乳房x线摄影特征的浸润性乳腺癌远端无复发生存预后模型的发展和内部验证。

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-04-20 DOI: 10.1038/s41523-026-00946-9

Jim Peters, Bas B L Penning de Vries, Jos A A M van Dijck, Ritse M Mann, Nikita Moriakov, Jonas Teuwen, Nico Karssemeijer, Esther H Lips, Jelle Wesseling, Merle M van Leeuwen, Alexandra W van den Belt-Dusebout, Carla H van Gils, Ruud Pijnappel, Linda de Munck, Marja van Oirsouw, Ellen Verschuur, Sjoerd G Elias, Mireille J M Broeders

{"title":"Development and internal validation of mammography feature-based prognostic models for distant recurrence-free survival of invasive breast cancer in a screening cohort.","authors":"Jim Peters, Bas B L Penning de Vries, Jos A A M van Dijck, Ritse M Mann, Nikita Moriakov, Jonas Teuwen, Nico Karssemeijer, Esther H Lips, Jelle Wesseling, Merle M van Leeuwen, Alexandra W van den Belt-Dusebout, Carla H van Gils, Ruud Pijnappel, Linda de Munck, Marja van Oirsouw, Ellen Verschuur, Sjoerd G Elias, Mireille J M Broeders","doi":"10.1038/s41523-026-00946-9","DOIUrl":"10.1038/s41523-026-00946-9","url":null,"abstract":"Overdiagnosis in breast cancer screening may be reduced by identifying lesions that, although detected on screening mammograms, are unlikely to progress to poor outcomes and may not require recall. As a proof-of-concept, we evaluated prognostic models for 10-year distant recurrence-free survival (DRFS) using radiomics features from invasive breast cancers (IBCs) presenting as masses on screening mammograms. In a cohort of screened women, 1466 IBC patients with clinical, pathological, and follow-up data were identified through national registries. Using radiomics features, tumor volume, and specific growth rate, proportional hazards models were developed to predict 10-year distant recurrence risk. Models were trained using positive screening mammograms of patients with screen-detected IBC (n = 1063) and diagnostic mammograms of patients with interval cancer (n = 406). Performance was evaluated only in screen-detected IBCs using repeated nested cross-validation. Median follow-up was 5.1 years (10th-90th percentile: 2.1-10.1), with 111 distant recurrences within 10 years. Model performance was moderate (C-index 0.70 [SD 0.01], calibration slope 1.22 [SD 0.13]), with predicted 10-year recurrence risks ranging from 4.9% to 18.0% (10th-90th percentile). The 42 IBCs with the lowest predicted risk had a 10-year recurrence probability of 2.6% (95% CI 0-7.5%), of whom only five received adjuvant systemic therapy. These findings suggest that mammography-based radiomics features may help identify low-risk IBCs and potentially reduce overdiagnosis by reconsidering recall for selected cases.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13280345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729651","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

Comparison of T-DXd-associated pulmonary toxicity in real-world settings and clinical trials. t - dxd相关肺毒性在现实环境和临床试验中的比较。

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-04-17 DOI: 10.1038/s41523-026-00936-x

Simon Udovica, Rupert Bartsch, Christian F Singer, Clemens Leitgeb, Maximilian Marhold, Christian Peters-Engl, Verena Sagaster, Maximilian Hochmair, Muna Ferner, Wolfgang Hilbe, Kathrin Strasser-Weippl

{"title":"Comparison of T-DXd-associated pulmonary toxicity in real-world settings and clinical trials.","authors":"Simon Udovica, Rupert Bartsch, Christian F Singer, Clemens Leitgeb, Maximilian Marhold, Christian Peters-Engl, Verena Sagaster, Maximilian Hochmair, Muna Ferner, Wolfgang Hilbe, Kathrin Strasser-Weippl","doi":"10.1038/s41523-026-00936-x","DOIUrl":"10.1038/s41523-026-00936-x","url":null,"abstract":"Interstitial lung disease (ILD) is a common and potentially life-threatening adverse event associated with trastuzumab deruxtecan (T-DXd). In the pivotal T-DXd clinical trials, 10-15% of patients developed ILD, with stringent mitigation strategies aimed at the early detection of low-grade cases. Real-world data are urgently needed to assess ILD incidence and outcomes outside controlled trial settings. This retrospective analysis included 190 patients treated with T-DXd at the Vienna Healthcare Group between August 2020 and December 2023. Among them, 17 (8.9%) developed any-grade ILD, with 8 cases (4.2% of the total cohort; 47.1% of ILD cases) classified as grade ≥3. The median time to ILD onset was 86 days, with a significantly shorter onset for high-grade compared to low-grade ILD (44.5 vs. 119 days, p = 0.01). A pooled real-world analysis (n = 1255, including patients from this study) demonstrated a higher incidence of high-grade ILD in real-world settings compared to phase III trials (2.9% vs. 1.4%, p = 0.014), despite no significant difference in overall ILD incidence (10.4% vs. 11.1%, p = 0.62). However, high-grade ILD rates in the real-world cohort were comparable to those reported in early phase I/II trials (2.9% vs. 3.5%, p = 0.41). These findings suggest a greater risk of high-grade ILD in real-world settings and underscore the need for rigorous patient selection, screening, and management strategies in clinical practice. Furthermore, the shorter onset of high-grade ILD suggests distinct pathophysiological mechanisms that warrant further investigation.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147717553","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

Acute circulating tumor DNA dynamics during and after systemic therapy initiation for advanced triple-negative breast cancer. 晚期三阴性乳腺癌开始全身治疗期间和之后的急性循环肿瘤DNA动力学。

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-04-16 DOI: 10.1038/s41523-026-00953-w

Briana To, Vishnu Prasath, Deloris Veney, Christian Rolfo, Viktor Adalsteinsson, William E Carson, Robert Wesolowski, Daniel Stover, Dionisia Quiroga

{"title":"Acute circulating tumor DNA dynamics during and after systemic therapy initiation for advanced triple-negative breast cancer.","authors":"Briana To, Vishnu Prasath, Deloris Veney, Christian Rolfo, Viktor Adalsteinsson, William E Carson, Robert Wesolowski, Daniel Stover, Dionisia Quiroga","doi":"10.1038/s41523-026-00953-w","DOIUrl":"10.1038/s41523-026-00953-w","url":null,"abstract":"Circulating tumor DNA (ctDNA) 'tumor fraction' (TF) may correlate with therapy response, but little is known regarding TF dynamics immediately after therapy initiation. Plasma samples from a single-arm clinical trial enrolling patients with triple-negative breast cancer were collected at a variety of time points following infusion of onalespib (day -7), paclitaxel (day 1), and onalespib + paclitaxel (day 8). 313 samples from 14 patients underwent shallow whole genome sequencing and TF determination. The primary objective was to evaluate TF change from pre-infusion to 6 h and 24 h post-infusion. There was significant TF decline from pre-infusion to 6 h for paclitaxel (p = 0.03) but no change for onalespib or onalespib+paclitaxel at 6hl. There was no ctDNA TF surge within minutes to 24 h of onalespib, paclitaxel, or combination, despite an overall decline in TF during the first therapy cycle. However, there was significant decline in TF from pre-infusion to D9 (16% to 6.5%, p = 0.004). These findings support further research on ctDNA dynamics immediately after therapy initiation.","PeriodicalId":19247,"journal":{"name":"NPJ Breast Cancer","volume":" ","pages":""},"PeriodicalIF":8.4,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13260934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147699266","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

Functional assays for BRCA1 and BRCA2 variant analysis: new tools and their applications. BRCA1和BRCA2变异分析的功能分析：新工具及其应用

IF 8.4 2区医学

NPJ Breast Cancer Pub Date : 2026-04-15 DOI: 10.1038/s41523-026-00949-6

Muthiah Bose, Elangoli Ebrahimkutty Faseela, Maria Rossing, Claus Storgaard Sørensen

引用次数: 0