Ines Mesa-Eguiagaray, Sarah H Wild, Linda J Williams, Kai Jin, Sheila M Bird, David H Brewster, Peter S Hall, Jonine D Figueroa
{"title":"Breast cancer-specific survival by molecular subtype in different age groups of women in Scotland.","authors":"Ines Mesa-Eguiagaray, Sarah H Wild, Linda J Williams, Kai Jin, Sheila M Bird, David H Brewster, Peter S Hall, Jonine D Figueroa","doi":"10.1186/s13058-025-02012-x","DOIUrl":"https://doi.org/10.1186/s13058-025-02012-x","url":null,"abstract":"<p><strong>Background: </strong>Age and molecular subtypes are important prognostic factors in breast cancer (BC). Here, we explore how age and molecular subtypes influence BC survival in Scotland.</p><p><strong>Methods: </strong>We analysed data from 71,784 women diagnosed with invasive BC in Scotland between 1997 and 2016, with follow-up until 31st December 2018 (median follow-up time = 5.5 years). Cox models estimated Hazard Ratios (HR) for BC-specific death by age group (with women of screening age, 50-69 years old, as the reference) within each molecular subtype, adjusting for prognostic factors. The cumulative incidence function was plotted to account for competing risks.</p><p><strong>Results: </strong>During the study period, 37% of women died, with 53% of deaths attributed to BC. Women aged 70 + years had increased BC-specific death compared to women aged 50 to 69 years with the same subtype. HRs (95% CI) were 1.49 (1.23-1.80) for luminal A, 1.39 (1.14 to 1.69) for luminal B tumours and 1.49 (1.15 to 1.94) for triple negative breast cancer (TNBC). Women aged < 50 years had lower risk of BC death in luminal A subtype only, with HR of 0.66 (0.51-0.86) compared to women aged 50 to 69 years. Competing risks analysis showed higher cumulative incidence of death from non-BC causes, particularly for women aged 70 + years with hormone positive subtypes. Stage, treatment, and molecular subtype were the strongest prognostic factors for BC-specific mortality across all ages.</p><p><strong>Conclusions: </strong>Age influences BC-specific mortality particularly within luminal subtypes. In contrast, other tumour characteristics and treatment are key prognostic factors for non-luminal subtypes. Future studies should investigate other markers of BC mortality particularly among over 70-year-olds, who account for 60% of BC deaths in the UK.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"59"},"PeriodicalIF":7.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013176/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jiawei Dai, Mariya Rozenblit, Xiaoyue Li, Naing Lin Shan, Yueyue Wang, Shrikant Mane, Michal Marczyk, Lajos Pusztai
{"title":"Genomic alterations in normal breast tissues preceding breast cancer diagnosis.","authors":"Jiawei Dai, Mariya Rozenblit, Xiaoyue Li, Naing Lin Shan, Yueyue Wang, Shrikant Mane, Michal Marczyk, Lajos Pusztai","doi":"10.1186/s13058-025-02018-5","DOIUrl":"https://doi.org/10.1186/s13058-025-02018-5","url":null,"abstract":"<p><strong>Background: </strong>Normal breast tissues adjacent to cancer often harbor many of the same genomic alterations as the cancer itself. However, it remains unclear whether histologically normal breast tissues carry genomic changes related to cancer development years before a cancer diagnosis.</p><p><strong>Methods: </strong>Whole exome sequencing was performed to examine germline and somatic alterations in histologically normal breast tissues from women who subsequently developed breast cancer (n = 79, pre-diagnosis tissues) and compared these with results from breast tissues of women who did not (n = 81). No patient had germline mutations in cancer predisposition genes.</p><p><strong>Results: </strong>The pre-diagnosis tissues had significantly more high functional impact germline variants per sample than the healthy controls (P = 0.034), 36.5% of affected genes were cancer hallmark genes, among these 62.4% were involved with evading growth suppressors and 5.7% with genome instability. The average number of somatic mutations were similar between the two cohorts. Mutation signature analysis revealed COSMIC signatures 3 (associated with impaired homologous recombination) as a dominant signature more frequent in pre-diagnosis tissues. At gene and variant level, nine common germline polymorphisms in two immune regulatory genes, FCGBP and TPSBP2, and along with three somatic mutations in F13A1, FRY and TMLHE, were significantly more frequently mutated in the pre-diagnosis samples.</p><p><strong>Conclusions: </strong>Individuals who develop breast cancer have a higher germline variant burden in normal breast tissues leading to subtle deficiencies in DNA repair that in the context of other germline and somatic mutations could facilitate malignant transformation.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"60"},"PeriodicalIF":7.4,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12013151/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Seo Kim, Jeong Hoon Lee, Yousung Yeon, Doyeon An, Seok Jun Kim, Myung-Giun Noh, Suehyun Lee
{"title":"Predicting Nottingham grade in breast cancer digital pathology using a foundation model.","authors":"Jun Seo Kim, Jeong Hoon Lee, Yousung Yeon, Doyeon An, Seok Jun Kim, Myung-Giun Noh, Suehyun Lee","doi":"10.1186/s13058-025-02019-4","DOIUrl":"10.1186/s13058-025-02019-4","url":null,"abstract":"<p><strong>Background: </strong>The Nottingham histologic grade is crucial for assessing severity and predicting prognosis in breast cancer, a prevalent cancer worldwide. Traditional grading systems rely on subjective expert judgment and require extensive pathological expertise, are time-consuming, and often lead to inter-observer variability.</p><p><strong>Methods: </strong>To address these limitations, we develop an AI-based model to predict Nottingham grade from whole-slide images of hematoxylin and eosin (H&E)-stained breast cancer tissue using a pathology foundation model. From TCGA database, we trained and evaluated using 521 H&E breast cancer slide images with available Nottingham scores through internal split validation, and further validated its clinical utility using an additional set of 597 cases without Nottingham scores. The model leveraged deep features extracted from a pathology foundation model (UNI) and incorporated 14 distinct multiple instance learning (MIL) algorithms.</p><p><strong>Results: </strong>The best-performing model achieved an F1 score of 0.731 and a multiclass average AUC of 0.835. The top 300 genes correlated with model predictions were significantly enriched in pathways related to cell division and chromosome segregation, supporting the model's biological relevance. The predicted grades demonstrated statistically significant association with 5-year overall survival (p < 0.05).</p><p><strong>Conclusion: </strong>Our AI-based automated Nottingham grading system provides an efficient and reproducible tool for breast cancer assessment, offering potential for standardization of histologic grade in clinical practice.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"58"},"PeriodicalIF":7.4,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008962/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Retraction Note: Association of Life's Essential 8 cardiovascular health with breast cancer incidence and mortality according to genetic susceptibility of breast cancer: a prospective cohort study.","authors":"Yan Zhao, Yang Song, Xiangmin Li, Ayao Guo","doi":"10.1186/s13058-025-02021-w","DOIUrl":"https://doi.org/10.1186/s13058-025-02021-w","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"56"},"PeriodicalIF":7.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jun Du, Jun Shi, Dongdong Sun, Yifei Wang, Guanfeng Liu, Jingru Chen, Wei Wang, Wenchao Zhou, Yushan Zheng, Haibo Wu
{"title":"Machine learning prediction of HER2-low expression in breast cancers based on hematoxylin-eosin-stained slides.","authors":"Jun Du, Jun Shi, Dongdong Sun, Yifei Wang, Guanfeng Liu, Jingru Chen, Wei Wang, Wenchao Zhou, Yushan Zheng, Haibo Wu","doi":"10.1186/s13058-025-01998-8","DOIUrl":"https://doi.org/10.1186/s13058-025-01998-8","url":null,"abstract":"<p><strong>Background: </strong>Treatment with HER2-targeted therapies is recommended for HER2-positive breast cancer patients with HER2 gene amplification or protein overexpression. Interestingly, recent clinical trials of novel HER2-targeted therapies demonstrated promising efficacy in HER2-low breast cancers, raising the prospect of including a HER2-low category (immunohistochemistry, IHC) score of 1 + or 2 + with non-amplified in-situ hybridization for HER2-targeted treatments, which necessitated the accurate detection and evaluation of HER2 expression in tumors. Traditionally, HER2 protein levels are routinely assessed by IHC in clinical practice, which not only requires significant time consumption and financial investment but is also technically challenging for many basic hospitals in developing countries. Therefore, directly predicting HER2 expression by hematoxylin-eosin (HE) staining should be of significant clinical values, and machine learning may be a potent technology to achieve this goal.</p><p><strong>Methods: </strong>In this study, we developed an artificial intelligence (AI) classification model using whole slide image of HE-stained slides to automatically assess HER2 status.</p><p><strong>Results: </strong>A publicly available TCGA-BRCA dataset and an in-house USTC-BC dataset were applied to evaluate our AI model and the state-of-the-art method SlideGraph + in terms of accuracy (ACC), the area under the receiver operating characteristic curve (AUC), and F1 score. Overall, our AI model achieved the superior performance in HER2 scoring in both datasets with AUC of 0.795 ± 0.028 and 0.688 ± 0.008 on the USCT-BC and TCGA-BRCA datasets, respectively. In addition, we visualized the results generated from our AI model by attention heatmaps, which proved that our AI model had strong interpretability.</p><p><strong>Conclusion: </strong>Our AI model is able to directly predict HER2 expression through HE images with strong interpretability, and has a better ACC particularly in HER2-low breast cancers, which provides a method for AI evaluation of HER2 status and helps to perform HER2 evaluation economically and efficiently. It has the potential to assist pathologists to improve diagnosis and assess biomarkers for companion diagnostics.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"57"},"PeriodicalIF":7.4,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12008878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143995057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Minouk J Schoemaker, Taylor Ellington, Hazel B Nichols, Lauren B Wright, Michael E Jones, Katie M O'Brien, Clarice R Weinberg, Hans-Olov Adami, Laura Baglietto, Kimberly A Bertrand, Yu Chen, Jessica Clague DeHart, A Heather Eliassen, Graham G Giles, Serena C Houghton, Victoria A Kirsh, Roger L Milne, Julie R Palmer, Hannah Lui Park, Thomas E Rohan, Gianluca Severi, Xiao-Ou Shu, Rulla M Tamimi, Lars J Vatten, Elisabete Weiderpass, Walter C Willett, Anne Zeleniuch-Jacquotte, Wei Zheng, Dale P Sandler, Anthony J Swerdlow
{"title":"Central and peripheral adiposity and premenopausal breast cancer risk: a pooled analysis of 440,179 women.","authors":"Minouk J Schoemaker, Taylor Ellington, Hazel B Nichols, Lauren B Wright, Michael E Jones, Katie M O'Brien, Clarice R Weinberg, Hans-Olov Adami, Laura Baglietto, Kimberly A Bertrand, Yu Chen, Jessica Clague DeHart, A Heather Eliassen, Graham G Giles, Serena C Houghton, Victoria A Kirsh, Roger L Milne, Julie R Palmer, Hannah Lui Park, Thomas E Rohan, Gianluca Severi, Xiao-Ou Shu, Rulla M Tamimi, Lars J Vatten, Elisabete Weiderpass, Walter C Willett, Anne Zeleniuch-Jacquotte, Wei Zheng, Dale P Sandler, Anthony J Swerdlow","doi":"10.1186/s13058-025-01995-x","DOIUrl":"10.1186/s13058-025-01995-x","url":null,"abstract":"<p><strong>Background: </strong>Among premenopausal women, higher body mass index (BMI) is associated with lower breast cancer risk, although the underlying mechanisms are unclear. Investigating adiposity distribution may help clarify impacts on breast cancer risk. This study was initiated to investigate associations of central and peripheral adiposity with premenopausal breast cancer risk overall and by other risk factors and breast cancer characteristics.</p><p><strong>Methods: </strong>We used individual-level data from 14 prospective cohort studies to estimate hazard ratios (HRs) for premenopausal breast cancer using Cox proportional hazards regression. Analyses included 440,179 women followed for a median of 7.5 years (interquartile range: 4.0-11.3) between 1976 and 2017, with 6,779 incident premenopausal breast cancers.</p><p><strong>Results: </strong>All central adiposity measures were inversely associated with breast cancer risk overall when not controlling for BMI (e.g. for waist circumference, HR per 10 cm increase: 0.92, 95% confidence interval (CI): 0.90-0.94) whereas in models adjusting for BMI, these measures were no longer associated with risk (e.g. for waist circumference: HR 0.99, 95% CI: 0.95-1.03). This finding was consistent across age categories, with some evidence that BMI-adjusted associations differed by breast cancer subtype. Inverse associations for in situ breast cancer were observed with waist-to-height and waist-to-hip ratios and a positive association was observed for oestrogen-receptor-positive breast cancer with hip circumference (HR per 10 cm increase: 1.08, 95% CI: 1.10-1.14). For luminal B, HER2-positive breast cancer, we observed an inverse association with hip circumference (HR per 10 cm: 0.84, 95% CI: 0.71-0.98), but positive associations with waist circumference (HR per 10 cm: 1.18, 95% CI: 1.03-1.36), waist-to-hip ratio (HR per 0.1 units: 1.29, 95% CI: 1.15-1.45) and waist-to height ratio (HR per 0.1 units: 1.46, 95% CI: 1.17-1.84).</p><p><strong>Conclusions: </strong>Our analyses did not support an association between central adiposity and overall premenopausal breast cancer risk after adjustment for BMI. However, our findings suggest associations might differ by breast cancer hormone receptor and intrinsic subtypes.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"55"},"PeriodicalIF":7.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12001638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002931","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pharmacovigilance study of adverse reactions of anti-HER-2 drugs for the treatment of HER-2-positive breast cancer based on the FAERS database.","authors":"Jinming Han, Xiaohan Zhai, Xufeng Tao, Yunming Li, Ziqi Zhao, Zhan Yu, Deshi Dong, Shilei Yang, Linlin Lv","doi":"10.1186/s13058-025-02013-w","DOIUrl":"https://doi.org/10.1186/s13058-025-02013-w","url":null,"abstract":"<p><strong>Objective: </strong>There are three categories of drugs that treat human epidermal growth factor receptor type 2 (HER-2) positive breast cancer: monoclonal antibodies (mAbs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). The purpose of this study is to analyze and compare the adverse reactions of three classes of anti-HER-2 drugs to various body systems in patients based on the FDA Adverse Event Reporting System (FAERS).</p><p><strong>Methods: </strong>All data reports were extracted from the FAERS between 2004 and 2024. Data mining of adverse events associated with anti-HER-2 drugs was carried out using disproportionality analysis. A multivariate logistic regression analysis was conducted to explore the risk factors associated with AEs leading to hospitalization.</p><p><strong>Results: </strong>A total of 47,799 patients were screened for the three classes of drugs, among which ADC drugs caused the largest proportion of deaths. MAb has the strongest ADR signals associated with \"cardiac disorders\". Moreover, trastuzumab was associated with a greater risk of cardiotoxicity. Logistic regression analysis revealed that the treatment with mAbs should be wary of serious adverse reactions in \"infections and infestations\" and \"metabolism and nutrition disorders\". Moreover, \"endocrine disorders\" were the factor associated with the highest risk of prolonged hospitalization due to trastuzumab deruxtecan (T-DXd). The safety of tucatinib among TKI drugs is greater than that of other drugs.</p><p><strong>Conclusion: </strong>In general, from the perspective of the effects of the three classes of drugs on the various body systems of patients, we should focus on mAb-associated \"cardiac disorders\", ADC-associated \"hepatobiliary disorders\", \"respiratory, thoracic and mediastinal disorders\", and TKI-associated \"gastrointestinal disorders.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"54"},"PeriodicalIF":7.4,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11983758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144022268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lusine Yaghjyan, Yujing J Heng, Brian R Sardella, Divya Murthy, Matt B Mahoney, Bernard Rosner, Kornelia Polyak, Maisey Ratcliff, Rulla M Tamimi
{"title":"Associations of circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 with the expression of stem cell markers in benign breast tissue.","authors":"Lusine Yaghjyan, Yujing J Heng, Brian R Sardella, Divya Murthy, Matt B Mahoney, Bernard Rosner, Kornelia Polyak, Maisey Ratcliff, Rulla M Tamimi","doi":"10.1186/s13058-025-02002-z","DOIUrl":"10.1186/s13058-025-02002-z","url":null,"abstract":"<p><strong>Background: </strong>The insulin-like growth factor (IGF) pathway is implicated in a naturally occurring process of tissue remodeling during which cells acquire stem cell-like characteristics. We examined associations of circulating IGF-1 and IGF binding protein-3 (IGFBP-3) with expression of CD44, CD24, and ALDH1A1 stem cell markers in benign breast biopsies.</p><p><strong>Methods: </strong>This study included 151 cancer-free women with incident biopsy-confirmed benign breast disease and blood samples within the Nurses' Health Study II. The data on reproductive and other BCa risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was done on tissue microarrays. For each core, the IHC expression was assessed using QuPath, and expressed as % of cells that stain positively for a specific marker out of the total cell count. Generalized linear regression was used to examine the associations of plasma IGF-I and IGFBP-3 (continuous log-transformed and quartiles) with log-transformed expression of each marker (in epithelium and stroma), adjusted for BCa risk factors.</p><p><strong>Results: </strong>In multivariate analysis, continuous circulating IGF-1 and IGFBP-3 measures were not associated with the continuous expression of any of the markers in the epithelium or stroma. Women whose IGFBP-3 levels were in the top quartile appeared to have lower expression of stromal CD24 compared to those in the lowest quartile (β = - 0.38, 95% CI - 0.69, - 0.08, p-trend = 0.06).</p><p><strong>Conclusions: </strong>Higher circulating IGFBP-3 levels were associated with lower stromal CD24 expression in benign breast tissue. Our findings provide indirect evidence of the inducing effect of IGF pathway on epithelial-to-mesenchymal transitions and stem cell activity in the breast.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"53"},"PeriodicalIF":7.4,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11978140/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143804496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Siyao Du, Wanfang Xie, Si Gao, Ruimeng Zhao, Huidong Wang, Jie Tian, Jiangang Liu, Zhenyu Liu, Lina Zhang
{"title":"Early prediction of neoadjuvant therapy response in breast cancer using MRI-based neural networks: data from the ACRIN 6698 trial and a prospective Chinese cohort.","authors":"Siyao Du, Wanfang Xie, Si Gao, Ruimeng Zhao, Huidong Wang, Jie Tian, Jiangang Liu, Zhenyu Liu, Lina Zhang","doi":"10.1186/s13058-025-02009-6","DOIUrl":"10.1186/s13058-025-02009-6","url":null,"abstract":"<p><strong>Background: </strong>Early prediction of treatment response to neoadjuvant therapy (NAT) in breast cancer patients can facilitate timely adjustment of treatment regimens. We aimed to develop and validate a MRI-based enhanced self-attention network (MESN) for predicting pathological complete response (pCR) based on longitudinal images at the early stage of NAT.</p><p><strong>Methods: </strong>Two imaging datasets were utilized: a subset from the ACRIN 6698 trial (dataset A, n = 227) and a prospective collection from a Chinese hospital (dataset B, n = 245). These datasets were divided into three cohorts: an ACRIN 6698 training cohort (n = 153) from dataset A, an ACRIN 6698 test cohort (n = 74) from dataset A, and an external test cohort (n = 245) from dataset B. The proposed MESN allowed for the integration of multiple timepoint features and extraction of dynamic information from longitudinal MR images before and after early-NAT. We also constructed the Pre model based on pre-NAT MRI features. Clinicopathological characteristics were added to these image-based models to create integrated models (MESN-C and Pre-C), and their performance was evaluated and compared.</p><p><strong>Results: </strong>The MESN-C yielded area under the receiver operating characteristic curve (AUC) values of 0.944 (95% CI: 0.906 - 0.973), 0.903 (95%CI: 0.815 - 0.965), and 0.861 (95%CI: 0.811 - 0.906) in the ACRIN 6698 training, ACRIN 6698 test and external test cohorts, respectively, which were significantly higher than those of the clinical model (AUC: 0.720 [95%CI: 0.587 - 0.842], 0.738 [95%CI: 0.669 - 0.796] for the two test cohorts, respectively; p < 0.05) and Pre-C (AUC: 0.697 [95%CI: 0.554 - 0.819], 0.726 [95%CI: 0.666 - 0.797] for the two test cohorts, respectively; p < 0.05). High AUCs of the MESN-C maintained in the ACRIN 6698 standard (AUC = 0.853 [95%CI: 0.676 - 1.000]) and experimental (AUC = 0.905 [95%CI: 0.817 - 0.993]) subcohorts, and the interracial and external subcohort (AUC = 0.861 [95%CI: 0.811 - 0.906]). Moreover, the MESN-C increased the positive predictive value from 48.6 to 71.3% compared with Pre-C model, and maintained a high negative predictive value (80.4-86.7%).</p><p><strong>Conclusion: </strong>The MESN-C using longitudinal multiparametric MRI after a short-term therapy achieved favorable performance for predicting pCR, which could facilitate timely adjustment of treatment regimens, increasing the rates of pCR and avoiding toxic effects.</p><p><strong>Trial registration: </strong>Trial registration at https://www.chictr.org.cn/ .</p><p><strong>Registration number: </strong>ChiCTR2000038578, registered September 24, 2020.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"52"},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phenotypes and cytokines of NK cells in triple-negative breast cancer resistant to checkpoint blockade immunotherapy.","authors":"Youlong Wang, Yongluo Jiang, Fadian Ding, Jun Lu, Tong Huang, Guanqing Zhong, Pengfei Zhu, Yue Ma, Jin Li, Xinjia Wang, Jiacai Lin, Hongjun Zheng, Weidong Wang, Yiwei Xu, Xiajie Lyu, Yu Si Niu, Xin Qi, Jinjian Li, Bocen Chen, Tingting He, Jiling Zeng, Yifei Ma","doi":"10.1186/s13058-025-02003-y","DOIUrl":"10.1186/s13058-025-02003-y","url":null,"abstract":"<p><p>Neoadjuvant checkpoint blockade immunotherapy (NATI) significantly prolonged outcomes for triple-negative breast cancer (TNBC). Residual tumor cells that survive NATI represent high-risk cell populations with metastatic potential and usually evade immunosurveillance by NK cells. Using an 82-protein panel, we here profiled single-cell membrane proteomics of CD56+ (NCAM1+) NK cells from tumor, peri-cancerous tissue, as well as peripheral blood from 28 TNBC patients post-NATI of residual cancer burden II/III. Unsupervised clustering resulted in several distinct clusters: 2 tumor-infiltrating NK (TINK) clusters with divergent functions of immune activation (TNFRSF7+) and suppression (SELL+); 2 immuno-suppressive peri-cancerous clusters; and 1 periphery-specific cluster. Considering the contradiction of the 2 TINK clusters, we further tested cytokine functions of SELL + and TNFRSF7 + TINKs by single-cell secreting proteomics using a 32-cytokine panel. Consistently, SELL + TINK clusters were characterized by immuno-suppressive secretion patterns (IL10+). A low proportion of SELL + TINK cluster and low proportion of IL10 + secreting SELL + TINK cluster (single-cell secreting proteomics) were both associated with better progression-free survival time. These findings were validated in an independent cohort of 15 patients during 16-month follow-up. Overall, we identified a distinct immuno-suppressive TINK cell group, featuring IL10 + secreting and SELL expression with a strong relation to poor survival prognosis in TNBC patients post-NATI.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"51"},"PeriodicalIF":7.4,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11969778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143781865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}