Breast Cancer Research最新文献

{"title":"Mammographic density by time and breast: a retrospective cohort study from BreastScreen Norway.","authors":"Nataliia Moshina, Jonas Gjesvik, Tone Hovda, Henrik W Koch, Heinrich A Backmann, Solveig Hofvind","doi":"10.1186/s13058-025-02037-2","DOIUrl":"https://doi.org/10.1186/s13058-025-02037-2","url":null,"abstract":"<p><strong>Background: </strong>Mammographic density is known to decrease over time in postmenopausal women. Longitudinal changes in mammographic density prior to breast cancer diagnosis have been widely discussed and less density reduction has been observed for breast developing versus not developing cancer. We aimed to verify these findings among participants of BreastScreen Norway.</p><p><strong>Methods: </strong>In this retrospective cohort study, data from 78,182 women aged 50-69 years who attended three consecutive screening rounds between 2007 and 2020 were included. Among those women, 970 were diagnosed with screen-detected and 308 with interval cancer. Mammographic density data was obtained from an automated software and included absolute (cm³) and percent (%) dense volume for each breast and for each woman, per examination. A linear mixed-effects regression model estimating differences in density between the breast developing and not developing cancer was applied to evaluate longitudinal changes, separately for absolute and percent dense volume. The model was adjusted for age at first screening examination, breast volume, follow-up time, history of benign breast disease, body mass index, family history, hormone therapy, use of alcohol and smoking. Results were presented as linear regression coefficient estimates with 95% confidence intervals (CI).</p><p><strong>Results: </strong>Mean age at the third screening examination for women without breast cancer was 62.5 (standard deviation, SD: 5.1) years, while mean age at diagnosis was 62.3 (SD: 4.4) years for women with screen-detected cancer and 61.9 (SD: 4.8) years for women with interval cancer. In our model, absolute and percent dense volume decreased with follow-up time, estimate=-0.010 (95%CI -0.010; -0.009) and estimate=-0.013 (95%CI -0.014; -0.013), respectively, indicating the overall negative effect of time on mammographic density. The interaction between time and development of breast cancer was positive for absolute and percent dense volume, estimate = 0.009 (95%CI 0.004; 0.014) for both, which implied that mammographic density in breasts developing cancer was stable or slightly decreasing.</p><p><strong>Conclusions: </strong>Less reduction in longitudinally assessed mammographic density was observed for breasts developing versus not developing cancer in our study. This difference might be used for more precise 4-6 years breast cancer risk prediction and screening personalization.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"83"},"PeriodicalIF":7.4,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD105⁺ fibroblasts support an immunosuppressive niche in women at high risk of breast cancer initiation.","authors":"Eric G Carlson, Jennifer C Lopez, Yukiko Yamaguchi, Jackson Gibson, Saul J Priceman, Mark A LaBarge","doi":"10.1186/s13058-025-02040-7","DOIUrl":"10.1186/s13058-025-02040-7","url":null,"abstract":"<p><strong>Background: </strong>Aging is the greatest risk factor for breast cancer, and although epithelial cells are the source of carcinomas, epithelial changes alone do not fully explain cancer susceptibility. Fibroblasts and macrophages are key stromal constituents around the cells of origin for cancer in breast tissue. With age, macrophages surrounding terminal ductal lobular units (TDLUs) become increasingly immunosuppressive. CD105⁺ fibroblasts intercalate within TDLUs, drive luminal differentiation, and give rise to immunosuppressive cancer-associated fibroblasts in other tissues. We propose that differences in fibroblasts are a crucial component of the stroma that shapes cancer susceptibility.</p><p><strong>Methods: </strong>Primary peri-epithelial fibroblast cultures were established from prophylactic and reduction mammoplasties from 30 women ranging in age from 16 to 70 years and from BRCA1 mutation carriers. Growth characteristics, transcriptional profiles, differentiation potential, and secreted proteins were profiled for fibroblast subtypes from diverse donors. Co-cultures with fibroblasts, macrophages, and T cells were used to ascertain the functional role played by CD105⁺ fibroblasts in immune cell modulation.</p><p><strong>Results: </strong>We found that peri-epithelial CD105⁺ fibroblasts are enriched in older women as well as women who carry BRCA1 mutations. These CD105⁺ fibroblasts exhibit robust adipogenesis and secrete factors related to macrophage polarization. Macrophages cocultured with fibroblasts better maintain or enhance polarization states than media alone. CD105⁺ fibroblasts increased expression of immunosuppressive macrophage genes. CD105⁺ fibroblasts supported anti-inflammatory macrophage-mediated suppression of T cell proliferation, whereas CD105^- fibroblasts significantly reduced the suppressive effect of anti-inflammatory macrophages on T cell proliferation.</p><p><strong>Conclusions: </strong>Establishment of a coculture system to dissect the molecular circuits between CD105⁺ fibroblasts and macrophages that drive immunosuppressive macrophage polarization has broad utility in understanding mammary gland development and events that precede cancer initiation. CD105⁺ fibroblasts and macrophages may coordinate to suppress immunosurveillance and increase breast cancer susceptibility.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"81"},"PeriodicalIF":7.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081442","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":"Depression, antidepressant use, and breast cancer incidence in the Sister Study cohort.","authors":"Mary V Díaz-Santana, Jihye Park, Molly Rogers, Katie M O'Brien, Hazel B Nichols, Aimee A D'Aloisio, Deborah B Bookwalter, Dale P Sandler, Clarice R Weinberg","doi":"10.1186/s13058-025-02043-4","DOIUrl":"10.1186/s13058-025-02043-4","url":null,"abstract":"<p><strong>Background: </strong>Depression could affect breast cancer risk; however, epidemiologic findings are mixed. We assessed the association of breast cancer risk with self-reported history of diagnosed depression and time-dependent antidepressant use.</p><p><strong>Methods: </strong>We analyzed data from 45,746 women in the Sister Study cohort (2003-2009). Cox proportional hazard regression was used to estimate hazard ratios (HR) for breast cancer.</p><p><strong>Results: </strong>During follow-up (mean = 11.7 years), 3,899 breast cancers were diagnosed. There was no association between history of diagnosed depression and risk of breast cancer (HR = 0.98, 95%CI = 0.91-1.06). However, antidepressant use was associated with reduced risk of breast cancer (HR = 0.92, 95%CI = 0.85-1.00). Comparison of antidepressant drug classes revealed a suggestion of an inverse association with selective serotonin reuptake inhibitors (SSRIs, HR = 0.90, 95%CI = 0.81-1.00). Reduction was stronger in those with BMI < 25 (HR = 0.72, 95%CI = 0.59-0.89).</p><p><strong>Conclusions: </strong>Depression was not associated with breast cancer risk. We observed a suggestion of a reduction in risk associated with antidepressant use. The analysis evaluating the association by specific drug types, showed a suggestion of a reduction in breast cancer risk associated with use of SSRIs. The negative association with overall antidepressant use and SSRIs, was stronger in those with BMI < 25, which could reflect a dose effect. This was the first study to examine the association between depression, antidepressant use, and breast cancer risk in a large genetic-risk-enriched cohort.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"82"},"PeriodicalIF":7.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12083028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081448","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":"Optimizing breast lesions diagnosis and decision-making with a deep learning fusion model integrating ultrasound and mammography: a dual-center retrospective study.","authors":"Ziting Xu, Shengzhou Zhong, Yang Gao, Jiekun Huo, Weimin Xu, Weijun Huang, Xiaomei Huang, Chifa Zhang, Jianqiao Zhou, Qing Dan, Lian Li, Zhouyue Jiang, Ting Lang, Shuying Xu, Jiayin Lu, Ge Wen, Yu Zhang, Yingjia Li","doi":"10.1186/s13058-025-02033-6","DOIUrl":"https://doi.org/10.1186/s13058-025-02033-6","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to develop a BI-RADS network (DL-UM) via integrating ultrasound (US) and mammography (MG) images and explore its performance in improving breast lesion diagnosis and management when collaborating with radiologists, particularly in cases with discordant US and MG Breast Imaging Reporting and Data System (BI-RADS) classifications.</p><p><strong>Methods: </strong>We retrospectively collected image data from 1283 women with breast lesions who underwent both US and MG within one month at two medical centres and categorised them into concordant and discordant BI-RADS classification subgroups. We developed a DL-UM network via integrating US and MG images, and DL networks using US (DL-U) or MG (DL-M) alone, respectively. The performance of DL-UM network for breast lesion diagnosis was evaluated using ROC curves and compared to DL-U and DL-M networks in the external testing dataset. The diagnostic performance of radiologists with different levels of experience under the assistance of DL-UM network was also evaluated.</p><p><strong>Results: </strong>In the external testing dataset, DL-UM outperformed DL-M in sensitivity (0.962 vs. 0.833, P = 0.016) and DL-U in specificity (0.667 vs. 0.526, P = 0.030), respectively. In the discordant BI-RADS classification subgroup, DL-UM achieved an AUC of 0.910. The diagnostic performance of four radiologists improved when collaborating with the DL-UM network, with AUCs increased from 0.674-0.772 to 0.889-0.910, specificities from 52.1%-75.0 to 81.3-87.5% and reducing unnecessary biopsies by 16.1%-24.6%, particularly for junior radiologists. Meanwhile, DL-UM outputs and heatmaps enhanced radiologists' trust and improved interobserver agreement between US and MG, with weighted kappa increased from 0.048 to 0.713 (P < 0.05).</p><p><strong>Conclusions: </strong>The DL-UM network, integrating complementary US and MG features, assisted radiologists in improving breast lesion diagnosis and management, potentially reducing unnecessary biopsies.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"80"},"PeriodicalIF":7.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12080162/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081494","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":"ESR1 testing on FFPE samples from metastatic lesions in HR + /HER2- breast cancer after progression on CDK4/6 inhibitor therapy.","authors":"Konstantinos Venetis, Giulia Cursano, Roberta Scafetta, Pier Paolo Maria Berton Giachetti, Alberto Concardi, Elisa De Camilli, Marianna D'Ercole, Eltjona Mane, Chiara Frascarelli, Antonio Marra, Sara Gandini, Francesco Pepe, Simone Scagnoli, Silvia Maria Rossi, Raffaella Troiano, Elena Speziale, Carmine De Angelis, Giancarlo Troncone, Umberto Malapelle, Giuseppe Perrone, Andrea Botticelli, Giuseppe Viale, Giuseppe Curigliano, Elena Guerini Rocco, Carmen Criscitiello, Nicola Fusco","doi":"10.1186/s13058-025-02020-x","DOIUrl":"https://doi.org/10.1186/s13058-025-02020-x","url":null,"abstract":"<p><p>Mutations in ESR1 play a critical role in resistance to endocrine therapy (ET) in hormone receptor-positive (HR +)/HER2- metastatic breast cancer (MBC). Testing for ESR1 mutations is essential for guiding treatment with novel oral selective estrogen receptor degraders (SERDs) like elacestrant or camizestrant. While most studies have utilized liquid biopsy (LB) for mutation detection, the role of formalin-fixed paraffin-embedded (FFPE) tissue biopsy in this context remains unclear. In this study, we analyzed a cohort of HR + /HER2- MBC patients who experienced resistance to ET and CDK4/6 inhibitors. Next-generation sequencing (NGS) was performed on FFPE biopsy samples obtained from metastatic sites at the time of disease progression. ESR1 mutations were detected in 24 out of 38 patients (63.2%), with p.D538G identified in 10 patients (45.5%) and p.Y537S in 6 patients (27.2%) as the most frequent alterations. One patient exhibited dual ESR1 mutations, and a recurrent ESR1-CCDC170 gene fusion was identified, underscoring the diversity and potential interplay of genetic alterations driving resistance in HR + /HER2- MBC. Notably, lung metastases were significantly more common in ESR1 mutant cases (8/24, 33.3%) compared to wild-type cases (1/14, 7.1%), while liver metastases showed no difference between mutant (12/24, 50.0%) and wild-type groups (7/14, 50.0%). Co-mutations in actionable pathways, particularly PIK3CA, were observed in n = 10 ESR1 mutant tumors (41.6%), highlighting their contribution to resistance mechanisms and posing significant challenges for treatment selection, as these alterations may necessitate combination therapies to effectively target multiple resistance pathways. This study presents new insights into the prevalence and clinical significance of ESR1 mutations in HR + /HER2- MBC, highlighting the potential utility of FFPE biopsy samples as a viable alternative or complementary approach to LB for mutation detection, particularly in resource-limited settings where access to ctDNA analysis may be constrained.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"79"},"PeriodicalIF":7.4,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12079830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144081489","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":"Cancers missed, women dismissed yet persist: natural language processing of online forums.","authors":"Kathleene T Ulanday, Maxim Topaz, Jeanette Shekelle, Marley Gibbons, Desiree Walker, Paula M Castaño, Amanda Nixon, Stacy Lewis, Mary Beth Terry, Lauren C Houghton","doi":"10.1186/s13058-025-01985-z","DOIUrl":"10.1186/s13058-025-01985-z","url":null,"abstract":"<p><strong>Objective: </strong>To identify gaps and delays in the detection of early onset cancer.</p><p><strong>Methods: </strong>We examined firsthand experiences shared on an online discussion board hosted by the Young Survival Coalition-an advocacy group for young adults diagnosed with breast cancer-spanning the years 2009 to 2019. We used natural language processing to detect codes: \"first signs and symptoms,\" \"steps to diagnosis,\" \"healthcare interactions,\" \"patient-provider-system feelings,\" and \"staging/type.\" In the training dataset, we used qualitative content analysis to code text from 750 of the forum's 571,914 posts. We developed and evaluated automated approaches to quantify the proportion of codes in all posts. Lastly, we qualitatively reviewed the classified posts to identify areas for improvement along the clinical pathway.</p><p><strong>Results: </strong>The vast majority (81%) of young adults self-detected their breast cancer rather than the cancer being detected through a clinical breast exam. Young adults (70%) were dissatisfied with their care because they encountered delays at three crossroads along the clinical pathway: 1) whether the clinician ordered tests or dismissed the individual as too young; 2) whether imaging modalities were sensitive or not; 3) whether a biopsy confirmed or missed the cancer. Mental health challenges and parenting pressures compounded these delays. True positive cases who experienced these delays strongly encouraged their peers to self-advocate, persist and insist on further testing until diagnosed accurately.</p><p><strong>Conclusion: </strong>Dismissal and delays in diagnosis of early onset breast cancer mean potentially worse prognosis since later stage cancers are more aggressive with fewer treatment options. The perspectives from survivors highlight the need for more research informing early detection in young adults by considering breast awareness, use of MRI and ultrasound, biopsy referrals for exhibited breast symptoms in the absence of positive imaging, and sociomedical support for individuals in their role as current or future parent.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"78"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12076973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144002894","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":"Association between transcriptomic metrics of exogenous antigen presentation and adaptive immunity with locoregional recurrence in localized estrogen receptor negative breast cancer: retrospective review of multi-institutional datasets.","authors":"Timothy J Robinson, Casey L Liveringhouse, Christopher Wilson, Sam Friedman, Justyn Nakashima, Matthew N Mills, Jacob D Purcell, Nicholas B Figura, Du Dongliang, Ram Thapa, Eric Welsh, Kamran A Ahmed, G Daniel Grass, Brooke L Fridley, Roberto Diaz","doi":"10.1186/s13058-025-01987-x","DOIUrl":"10.1186/s13058-025-01987-x","url":null,"abstract":"<p><strong>Background: </strong>Transcriptomic features of breast cancer locoregional recurrence (LRR) remain poorly understood. We therefore sought to investigate transcriptomic features associated with LRR in newly diagnosed invasive breast tumors from our institutional dataset.</p><p><strong>Methods: </strong>Transcriptomic profiling was performed on 632 tumors from consecutive patients treated within our health system for newly diagnosed non-metastatic breast cancer. Univariable Cox models identified genes whose expression was associated with LRR (q-value < 0.05). Up-regulated (UR) genes were defined as hazard ratio (HR) > 1 and down-regulated (DR) genes were defined as HR < 1. Gene set enrichment analyses were performed for UR and DR gene sets and validated within two external cohorts of ER- tumors.</p><p><strong>Results: </strong>With a median follow-up of 7.6 years, we observed 38 LRRs: 28/481 (5.8%) in ER + and 10/151 (6.6%) in ER-. There were 43 UR and 7 DR genes associated with LRR in ER + tumors, while 417 UR and 1150 DR genes were associated with LRR in ER- tumors. UR genes in ER + tumors were enriched for roles in cell proliferation (q < 0.05). In contrast, LRR in ER- tumors was most strongly associated with DR genes enriched for MHC-II-mediated antigen presentation and T cell activation (q < 0.05). In external cohorts of ER- tumors, 97 significant DR genes (p < 0.05) were enriched for 18 pathways, including 5 pathways involved in MHC-II signaling, antigen presentation and T-cell activation.</p><p><strong>Conclusions: </strong>Transcriptomic patterns associated with LRR appear distinct between ER + and ER- tumors. In ER + tumors, LRR appears predominantly associated with proliferation, whereas ER- LRR suggests a robust pattern of suppressed antigen presentation via MHC-II.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"77"},"PeriodicalIF":7.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023940","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: Tamoxifen suppresses brain metastasis of estrogen receptor-deficient breast cancer by skewing microglia polarization and enhancing their immune functions.","authors":"Shih-Ying Wu, Sambad Sharma, Kerui Wu, Abhishek Tyagi, Dan Zhao, Ravindra Pramod Deshpande, Kounosuke Watabe","doi":"10.1186/s13058-025-02042-5","DOIUrl":"10.1186/s13058-025-02042-5","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"75"},"PeriodicalIF":7.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046828","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":"Prognostic value of cancer-related fatigue at the end of radiotherapy for overall survival ≥ 10 years in women with breast cancer.","authors":"Philipp Heumann, Axel Benner, Sabine Behrens, Jenny Chang-Claude, Petra Seibold","doi":"10.1186/s13058-025-02036-3","DOIUrl":"10.1186/s13058-025-02036-3","url":null,"abstract":"<p><strong>Background: </strong>Cancer-related fatigue (CRF) is a common symptom in breast cancer patients and survivors, which can substantially impair quality of life. Previous studies suggested that CRF may be associated with poorer survival outcomes, but had limited follow-up duration or insufficient adjustment for established prognostic factors. The aim of this analysis was to assess the prognostic value of CRF at the end of radiotherapy for overall survival in a cohort of women with breast cancer with a median follow-up time of 19 years.</p><p><strong>Methods: </strong>Data from the prospective ISE study, which enrolled women with non-metastatic breast cancer between 1998 and 2001, were analysed. Patients did not receive chemotherapy. A vital status follow-up was conducted in 2019. CRF was collected at the end of radiotherapy using the EORTC QLQ-C30 and classified using the threshold of clinical importance. Cox regression models adjusted for CRF, age, body mass index (BMI), tumour size, nodal involvement, grading and receptor status were calculated.</p><p><strong>Results: </strong>Of 437 patients with fatigue assessments, 164 (38%) reported CRF. During 10 years of follow-up, 25 patients without and 27 patients with CRF died. Tumour size, nodal involvement and age were statistically significantly associated with 10-year overall survival. For CRF, a statistically significant effect was observed for ≥ 5 years of follow-up (HR: 2.44), but not within the first 5 years of follow-up (HR: 1.26).</p><p><strong>Conclusions: </strong>CRF assessments at the end of radiotherapy showed prognostic value for long-term survival beyond established factors and could potentially be used to identify patients that require monitoring in risk-adapted aftercare programmes in order to improve survival.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"76"},"PeriodicalIF":7.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12070715/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144046826","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":"Denosumab as an immune modulator in HER2-negative early breast cancer: results of the window-of-opportunity D-BIOMARK clinical trial.","authors":"Andrea Vethencourt, Eva M Trinidad, Eduard Dorca, Anna Petit, M Teresa Soler-Monsó, Marina Ciscar, Alexandra Barranco, Gema Pérez-Chacón, María Jimenez, Mario Rodríguez, Clara Gomez-Aleza, Elvira Purqueras, Enrique Hernández-Jiménez, Ander Urruticoechea, Idoia Morilla, Isaac Subirana, Amparo García-Tejedor, Miguel Gil-Gil, Sonia Pernas, Catalina Falo, Eva Gonzalez-Suarez","doi":"10.1186/s13058-025-01996-w","DOIUrl":"https://doi.org/10.1186/s13058-025-01996-w","url":null,"abstract":"<p><strong>Background: </strong>The RANK pathway has been extensively investigated for its role in bone resorption; however, its significance extends beyond bone metabolism. Preclinical models suggest that inhibition of RANK signaling can prevent mammary tumor development by reducing proliferation and tumor cell survival. Additionally, both preclinical and clinical data support the ability of RANK pathway inhibitors to enhance the anti-tumor immune response.</p><p><strong>Methods: </strong>D-BIOMARK is a prospective, randomized window-of-opportunity clinical trial assessing the biological effects of denosumab, a monoclonal antibody against RANKL, in patients with HER2-negative early breast cancer. The study aims to assess denosumab's impact on breast tumor cell proliferation, apoptosis, and its potential to influence the tumor immune microenvironment. A total of 60 patients were enrolled and randomized 2:1 to receive two doses of single agent denosumab (120 mg one week apart) before surgery or to the control arm (no treatment). Fifty-eight patients were evaluated, 27 pre-menopausal and 31 post-menopausal women, 48 with luminal tumors and 10 with triple negative breast cancer. Paired tumor samples were collected to compare baseline (core biopsy) and surgical (surgical specimen) time points, as well as serum samples at both time points.</p><p><strong>Results: </strong>Denosumab demonstrated its ability to reduce serum free RANKL levels (experimental p < 0.001, control p = 0.270). However, a reduction in tumor cell proliferation or cell survival was not observed. A denosumab-driven increase in tumor infiltrating lymphocytes (TILs) was observed (experimental p = 0.001, control p = 0.060), particularly in the luminal B-like population (experimental p = 0.012, control p = 0.070) and a similar trend in the TNBC group (experimental p = 0.079, control p = 0.237). Denosumab led to increased TILs in both pre-menopausal (experimental p = 0.048, control p = 0.639) and post-menopausal (experimental p = 0.041, control p = 0.062) women with luminal tumors. RANK protein expression in tumor and stroma was associated with markers of tumor aggressiveness but an increase in TILs was observed in the experimental arm, irrespectively of RANK and RANKL expression in tumor or stromal cells.</p><p><strong>Conclusions: </strong>The D-BIOMARK trial suggests a potential role for denosumab as an immune-enhancing agent in early HER2-negative breast cancer. Although preoperative denosumab did not reduce tumor proliferation or increased apoptosis, it led to an increase in TILs, particularly in luminal B-like tumors. These findings underscore the importance of further investigation into the multifaceted aspects of the RANK pathway. Trial registration EudraCT number: 2016-002678-11 registered on June 15, 2018.</p><p><strong>Clinicaltrials: </strong>gov identifier: NCT03691311, retrospectively registered on September 04, 2018.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"68"},"PeriodicalIF":7.4,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12067755/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144053628","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}