Breast Cancer Research最新文献

{"title":"Hsa-miR-155-5p expression in primary breast tissue may have the potential for prediction of breast cancer brain recurrence: results from the multi-institutional exploratory cohort study.","authors":"Yoichi Koyama, Masako Muguruma, Yoshiya Horimoto, Kazutaka Narui, Akimitsu Yamada, Kimito Yamada, Shinya Yamamoto, Shunichiro Orihara, Hiroshi Kaise, Akiko Kogure, Yusuke Yoshioka, Takahiro Ochiya, Takashi Ishikawa","doi":"10.1186/s13058-025-02123-5","DOIUrl":"10.1186/s13058-025-02123-5","url":null,"abstract":"<p><strong>Background: </strong>Despite the known incidence of brain metastases in breast cancer, no useful biomarker has been clinically established for breast cancer brain metastasis (BCBM). In the present study, we aimed to examine the expression of microRNAs (miRNAs) related to BCBM in formalin-fixed paraffin-embedded (FFPE) tissues to identify their usefulness as predictive biomarkers of breast cancer brain recurrence (BCBR).</p><p><strong>Methods: </strong>Pairs of primary breast and metastatic site tissue samples were collected from 38 patients who experienced the first recurrence of metastasis to a single distant organ (brain/lungs/liver/bones = 11/12/9/6 patients) between January 2007 and December 2021 at five institutions in Japan. We evaluated the expression of 15 miRNAs in FFPE specimens of untreated breast and metastatic sites from the same patient using quantitative polymerase chain reaction.</p><p><strong>Results: </strong>Analysis of the selected 15 miRNAs revealed that hsa-miR-155-5p exhibited significant BCBR-specific overexpression in untreated primary breast tissues (p < 0.001). Two other miRNAs, hsa-miR-150-5p and hsa-miR-20b-5p, exhibited moderate (ρ = 0.587) and weak (ρ = 0.350) positive correlations with hsa-miR-155-5p, respectively. The BCBR prediction model demonstrated a high discrimination ability for hsa-miR-155-5p (AUC = 0.960). The localization of hsa-miR-155-5p in primary breast cancer tissue by in situ hybridization confirmed that hsa-miR-155-5p was uniformly stained in the breast cancer cells.</p><p><strong>Conclusions: </strong>Hsa-miR-155-5p expression in untreated primary breast tissue may be a valuable biomarker for predicting BCBR. A personalized escalation strategy is expected to be helpful in conquering brain metastases.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"169"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482611/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193629","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":"Development of a microRNA-based prognostic model for accurate prediction of distant metastasis in breast cancer patients.","authors":"Andrea Fontana, Raffaela Barbano, Barbara Pasculli, Tommaso Mazza, Orazio Palumbo, Elena Binda, Nadia Trivieri, Gandino Mencarelli, Ilaria Laurenzana, Daniela Lamorte, Luciana De Luca, Antonella Caivano, Tommaso Biagini, Michelina Rendina, Antonio Lo Mele, Giuseppina Prencipe, Sara Bravaccini, Roberto Murgo, Luigi Ciuffreda, Maria Morritti, Vanna Maria Valori, Francesca Sofia Di Lisa, Patrizia Vici, Marina Castelvetere, Massimo Carella, Paolo Graziano, Evaristo Maiello, Massimiliano Copetti, Manel Esteller, Paola Parrella","doi":"10.1186/s13058-025-02124-4","DOIUrl":"10.1186/s13058-025-02124-4","url":null,"abstract":"<p><strong>Background: </strong>The attempt to exploit molecular subtyping for risk stratification in breast cancer patients has been only partially successful with a limited application in the clinical practice. In the BREMIR study, we aimed to identify a panel of miRNAs as prognostic biomarkers for breast cancer. We first confirmed the association of previously linked miRNAs with critical clinical parameters, then adopted a discovery-driven approach to identify novel biomarkers.</p><p><strong>Methods: </strong>miRNA expression was analyzed using the Affymetrix Gene Chip 4.0 array in a discovery cohort of 34 patients (3 with synchronous metastases, 14 who developed metastases after 10 years, and 17 who remained metastasis-free) and 6 controls. RT-qPCR validated selected miRNAs in an extended cohort (n = 223) with a median follow up of 6.6 years. A stepwise logistic regression model incorporating miRNA levels and clinicopathological features was developed to predict metastasis risk. Additionally, miRNA expression was assessed in plasma extracellular vesicles (EVs) using digital PCR in an independent cohort (n = 39). In silico enrichment analyses explored the functional role of relevant miRNAs in metastasis development.</p><p><strong>Results: </strong>Eight differentially expressed miRNAs were identified in the discovery cohort. In the extended cohort, miR-3916 and miR-3613-5p were the most effective in distinguishing patients who developed metastases. Higher miR-3916 expression was associated with reduced metastasis risk (OR = 0.42, 95%CI 0.23-0.70, p = 0.002), while higher miR-3613-5p expression was linked to increased risk (OR = 2.06, 95%CI 1.27-3.50, p = 0.005). Adding these miRNAs to a model with clinicopathological features improved discrimination (AUC = 0.85 vs. AUC = 0.76, p = 0.001). The model was effective across all breast cancer subtypes. In extracellular vesicles, miR-3613-5p was more abundant in tumors than benign lesions (p = 0.039), while miR-3916 was lower in metastatic samples than in non-metastatic tumors (p = 0.020). In-silico pathway enrichment analyses indicates their involvement in critical steps of the metastatic process including EMT plasticity, DNA damage response and metastatic niche formation.</p><p><strong>Conclusions: </strong>This is the first study integrating miRNA expression with clinicopathological features in a logistic model for breast cancer prognosis. While further validation is needed, our model shows promise as a prognostic tool across all breast cancer subtypes. In silico pathway enrichment analysis highlights miR-3613-5p and miR-3916 as critical regulators of metastasis development, underscoring the need for further investigation.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov ID NCT06555354 retrospectively registered on August 14th, 2024.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"170"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193626","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":"Neoadjuvant therapy with eribulin, doxorubicin and cyclophosphamide for patients with HER2-negative inflammatory breast cancer: a phase II study.","authors":"Kristina Fanucci, Eren D Yeh, Ruichao Shi, Lei Qin, Camden P Bay, Molly DiLullo, Ashka Patel, McKenna Moore, Zachary T Herbert, Beth T Harrison, Faina Nakhlis, Jennifer Bellon, Laura Warren, Jennifer L Guerriero, Sara M Tolaney, Meredith Regan, Beth Overmoyer, Steven Van Laere, Filipa Lynce","doi":"10.1186/s13058-025-02108-4","DOIUrl":"10.1186/s13058-025-02108-4","url":null,"abstract":"<p><strong>Background: </strong>Inflammatory breast cancer (IBC) is an aggressive and highly angiogenic disease. Eribulin is a microtubule inhibitor with anti-angiogenic properties.</p><p><strong>Methods: </strong>In a phase II trial, we examined the efficacy of an eribulin-containing neoadjuvant regimen (eribulin- > doxorubicin plus cyclophosphamide (AC) or AC- > eribulin) for patients with newly diagnosed HER2-negative IBC. Pathologic complete response (pCR: ypT0/Tis ypN0) was the primary endpoint; residual cancer burden (RCB) categories were also recorded. Five patients from each cohort underwent dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted MRI. All patients had research breast biopsies for transcriptomic, differential gene expression, and cell subset analysis at baseline and one week after the first dose of therapy.</p><p><strong>Results: </strong>19/22 (86.4%) patients had hormone receptor-positive disease. All patients were able to undergo planned curative-intent surgery and radiation. One patient had a pCR, and long-term outcomes were encouraging: after median follow up of 76 months, 3 patients experienced disease recurrence. Five-year event-free survival (EFS) was 85.6%. The regimen was tolerated with expected side effects-the most common grade 1 or 2 AEs were fatigue (95.5%), nausea (68.2%), and alopecia (63.6%). Seven out of 22 (31.8%) patients experienced any grade 3 or 4 AE, with neutropenia (22.7%) being the most common. DCE-MRI showed decreased tumor vascularization after 1 week of treatment versus baseline. Transcriptomic analysis using quantification of synthesized dsDNA libraries and tumor microenvironment analysis of paired baseline and on-treatment samples showed residual cancer burden (RCB)-III tumors were more likely to have genes associated with adipogenesis/fatty acid metabolism and cells associated with immunosuppression.</p><p><strong>Conclusions: </strong>Despite the low pCR rate, all patients were able to undergo curative surgery, and long-term outcomes were encouraging with 5-year EFS 85.6%. Decreases in tumor vascularization with treatment were detected by DCE-MRI parameters irrespective of initial chemotherapy received. Adipogenesis/fatty acid metabolism and cells associated with immunosuppression are potential mechanisms of resistance and targets for future investigation in this unique patient population.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov (NCT02623972)(Registration date: 12/02/15).</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"171"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193591","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":"Interplay of BMI and volumetric breast density measures and breast cancer risk for black and white women.","authors":"Mattia A Mahmoud, Stacey J Winham, Christopher G Scott, Sarah Ehsan, Aaron D Norman, Matthew R Jensen, Emily F Conant, Karla M Kerlikowske, Despina Kontos, Celine M Vachon, Anne Marie McCarthy","doi":"10.1186/s13058-025-02120-8","DOIUrl":"10.1186/s13058-025-02120-8","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"167"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12482891/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193668","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":"Murine hindlimb lymphedema model: optimization and evaluation of radiation.","authors":"Shahnur Ahmed, Ganesh Mohan, Daniel J Konig, Steven J Sullivan, Christopher A Subi-Kasozi, Angad Sidhu, Miguel Jorge, Helen C Sinex, Marc S Mendonca, Mithun Sinha, Aladdin H Hassanein","doi":"10.1186/s13058-025-02112-8","DOIUrl":"10.1186/s13058-025-02112-8","url":null,"abstract":"<p><strong>Background: </strong>Post-surgical lymphedema frequently occurs following lymph node dissection. The murine tail is the most commonly used model to study secondary lymphedema. The murine hindlimb model offers a more clinically translatable approach but results in the literature have been inconsistent. The purpose of this study is to optimize the murine hindlimb lymphedema to achieve consistent results and assess the utility of radiation.</p><p><strong>Methods: </strong>C57BL/6 mice underwent either 20-Gy irradiation of one hindlimb 7 days prior to surgery (n = 11) or no radiation (n = 9). For all mice, a circumferential skin incision was created at the proximal hindlimb. Lymphatics were identified and disrupted. Popliteal lymph nodes were excised. Paw thickness was measured and near-infrared laser lymphangiography was used to assess lymphatic function.</p><p><strong>Results: </strong>The average paw thickness of the operated hindlimb in irradiated mice on postoperative day (POD) 14 was 3.5 ± 0.3 cm compared to 2.1 ± 0.05 cm on the contralateral limb (p = 0.0001). Lymphangiography on POD-42 showed significantly worse lymphatic function in the operated hindlimb compared to the control hindlimb (p = 0.003). For the non-radiated mice, the paw thickness was 2.5 ± 0.2 cm on POD-42 compared to the contralateral limb (2.1 ± 0.1 cm) (p = 0.0002) but smaller than radiated hindlimb group (3.2 ± 0.1 cm) (p = 0.0002). The nonradiated mice had significantly greater paw thickness than the control limb until POD-56 whereas the radiated mice sustained significant paw thickness to POD-90.</p><p><strong>Conclusion: </strong>Radiation of the murine hindlimb model results in sustained lymphedema compared to non-irradiated mice. The murine hindlimb lymphedema model is clinically more translatable than the murine tail model with consistent results.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"168"},"PeriodicalIF":5.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12481953/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145193614","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":"An enteropathogenic microbial toxin modulates the breast cancer epigenome resulting in concurrent silencing of tumor suppressor genes.","authors":"Deepak Verma, Deeptashree Nandi, Sheetal Parida, Archisha Saxena, Dipali Sharma","doi":"10.1186/s13058-025-02111-9","DOIUrl":"10.1186/s13058-025-02111-9","url":null,"abstract":"<p><strong>Background: </strong>Recent studies have determined a close association between host microbiota and breast cancer initiation, growth and therapeutic outcomes. We previously uncovered how enterotoxigenic Bacteroides fragilis (ETBF), a gut microbe present in malignant breast tissue, aids breast cancer development and metastatic progression via activating multiple oncogenic pathways and modulating breast tumor microenvironment. Brief exposure to ETBF-secreted toxin, BFT (Bacteroides fragilis toxin), imparts long-term oncogenic, pro-stemness and pro-metastasis memory in breast cancer cells indicating the involvement of epigenetic alterations hence, we aimed to investigate the potential involvement of epigenetics in biological impact of ETBF in breast cancer.</p><p><strong>Methods: </strong>RNA sequencing and Infinium methylation EPIC microarray were performed in mammary tumors developed from the BFT-exposed breast cancer cells. Alterations in the expression of tumor suppressor genes (TSGs) were assessed using RT-PCR, ICC and IHC. Demethylation agent and HDAC inhibitor were utilized to rescue the expression of BFT-mediated hypermethylated TSGs, and examine the migration/invasion potential of BFT-exposed breast cancer cells.</p><p><strong>Results: </strong>EPIC methylation microarray analysis of BFT-exposed mammary tumors uncovered 64 differentially methylated significant CpG sites whose analysis led to the identification of 26 hypomethylated and 156 hypermethylated genes. Of the hypermethylated genes, also showing reduced expression in RNA-seq in BFT-exposed group, we identified five important TSGs, namely, NF2, RSK3, FAT4, DCN and DOK2. Survival analysis revealed that decreased expression of these TSGs associated with worse prognosis. While BFT exposure reduced the expression of these TSGs, treatment with Azacytidine or/and Trichostatin A resulted in rescue of the TSGs from BFT-induced repression while mitigating BFT-driven migration and invasion of breast cancer cells.</p><p><strong>Conclusions: </strong>Collectively, BFT exposure epigenetically modifies the expression of TSGs and impacts migration/invasion potential of breast cancer cells, and treatment with demethylation agent(s) and HDAC inhibitors effectively diminishes the functional impact of BFT.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"163"},"PeriodicalIF":5.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179853","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":"AI-driven MRI biomarker for triple-class HER2 expression classification in breast cancer: a large-scale multicenter study.","authors":"Chinting Wong, Qi Yang, Yanting Liang, Zhitao Wei, Yi Dai, Zeyan Xu, Xiaobo Chen, Siyao Du, Chu Han, Changhong Liang, Lina Zhang, Zaiyi Liu, Ying Wang, Zhenwei Shi","doi":"10.1186/s13058-025-02118-2","DOIUrl":"10.1186/s13058-025-02118-2","url":null,"abstract":"","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"166"},"PeriodicalIF":5.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465374/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179817","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":"Trends in breast cancer death rates from ductal carcinoma in situ versus invasive cancer in the United States.","authors":"Hyuna Sung, Chenxi Jiang, Ismail Jatoi, Ahmedin Jemal","doi":"10.1186/s13058-025-02068-9","DOIUrl":"10.1186/s13058-025-02068-9","url":null,"abstract":"<p><strong>Background: </strong>Breast ductal carcinoma in situ (DCIS), considered a non-obligate precursor to invasive breast cancer, has been widely studied; however, trends in death rate from DCIS remain undocumented.</p><p><strong>Methods: </strong>To examine the trend in death rate from DCIS among women (age at death, 40 + years) in the US, we quantified annual percent changes (APCs) and average APCs in age-standardized death rates using the Surveillance, Epidemiology, and End Results Program (SEER) 8 incidence-based mortality database and Joinpoint regression. The trend was quantified from 2000 to 2021, capturing deaths among women diagnosed between 1975 and 2021 and allowing for a 25-year follow-back period before each death year. Additionally, we employed the SEER 12 to assess disparities in death rates from DCIS by race and ethnicity during 2017-2021, based on diagnoses from 1992-2021. Trends in death rates from invasive breast cancer were analysed similarly.</p><p><strong>Results: </strong>Death rate from DCIS increased by 2.43% annually (95% confidence interval [CI] = 1.34-3.54) from 2000-2015, and then plateaued, leading to an overall statistically non-significant increase from 2000-2021 (1.01% per year; 95%CI = -0.20-2.24). This trend was in stark contrast with an average of 1.61% annual decrease in death rates for invasive breast cancer (95%CI = -1.95 to -1.27). From 2016-2021, death rate from DCIS was 87% higher among non-Hispanic Black women than non-Hispanic White women (2.98 vs 1.60 per 100,000), a relatively larger disparity than the 39% estimated for death rate from invasive cancer (55.96 vs 40.28 per 100,000).</p><p><strong>Conclusions: </strong>Distinct epidemiologic patterns in death rates between DCIS and invasive breast cancer highlight important implications for understanding the natural history and management of these malignancies.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"164"},"PeriodicalIF":5.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179845","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":"Glutamine synthetase shields triple-negative breast cancer cells from ferroptosis in metastasis triggered by glutamine deprivation.","authors":"Zhaoting Yang, Xinyu Lian, Yuan Luo, Qiao Ye, Guangjin Guo, Guoquan Liu","doi":"10.1186/s13058-025-02115-5","DOIUrl":"10.1186/s13058-025-02115-5","url":null,"abstract":"<p><strong>Background: </strong>Epithelial-mesenchymal transition (EMT) in cancer cell metastasis involves complicated metabolic plasticity to survive the highly challenging environment, such as oxidative stress, after subsequent circulation in the bloodstream. Glutamine synthetase (GS) is an enzyme that converts glutamate and ammonia to glutamine (Gln) during Gln deprivation stress. This study revealed for the first time that GS plays an important role in protecting triple-negative breast cancer (TNBC) cells from ferroptosis during Gln deprivation-induced EMT, namely ferroptosis-resistant EMT (FR-EMT).</p><p><strong>Methods: </strong>To better understand this finding, we focused on the mechanism of GS-mediated FR-EMT in TNBC through transcriptomic analysis and murine metastasis modeling.</p><p><strong>Results: </strong>This study specifically investigated the effects of GS on lipid peroxidation and iron metabolism, the two major metabolic disorders in ferroptosis. An abnormal increase in monounsaturated fatty acids (MUFAs) mediated by mechanistic target of rapamycin complex 1 (mTORC1) decreased the ferroptosis sensitivity under Gln deprivation. Additionally, aberrant iron metabolism via lipocalin 2 (LCN2) and transferrin receptor (TFRC) affected the sensitivity to ferroptosis. Moreover, this study confirmed that GS protects TNBC cells from ferroptosis and increases their ability to survive during subsequent metastasis through the blood in the lung metastasis mouse model.</p><p><strong>Conclusion: </strong>This investigation provides insights into the role of ferroptosis in metastasis and demonstrates that GS may be a viable target for preventing metastases in TNBC.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"165"},"PeriodicalIF":5.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145179781","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":"A STAT1-GBP1 axis modulates epithelial proliferation in postpartum breast tissue by repressing CDKI expression.","authors":"Joshua W Ogony, Laura M Pacheco-Spann, Amanda Arnold, Jennifer V Cabezas, Nicole Cruz-Reyes, Camila Pacheco Erak, Pria J Westerman, Savanna A Touré, Sharoon Akhtar, Stacey J Winham, Sarah McLaughlin, Amy C Degnim, Mark E Sherman, Derek C Radisky","doi":"10.1186/s13058-025-02117-3","DOIUrl":"10.1186/s13058-025-02117-3","url":null,"abstract":"<p><strong>Background: </strong>Postpartum breast cancer, diagnosed within five years of childbirth, is associated with heightened mortality compared to breast cancers in nulliparous women. Although the postpartum breast undergoes extensive involution and remodeling, the molecular drivers that promote subsequent tumor development remain incompletely understood. We investigated whether signal transducer and activator of transcription 1 (STAT1) and guanylate binding protein 1 (GBP1) contribute to epithelial proliferation through suppression of cyclin-dependent kinase inhibitors (CDKIs).</p><p><strong>Methods: </strong>Formalin-fixed, paraffin-embedded postpartum (n = 5) and nulliparous (n = 5) benign breast tissues were profiled using transcriptomic panels targeting oncogenic and immunologic pathways. Protein expression of STAT1, GBP1, and the proliferation marker Ki67 was examined by immunohistochemistry. Functional studies were performed in human mammary epithelial cells (HMECs) derived from the same postpartum and nulliparous tissues. Small interfering RNA (siRNA) and lentiviral knockdown strategies were used to reduce STAT1 and GBP1, followed by assessment of CDKI expression, cell cycle distribution, and cell proliferation.</p><p><strong>Results: </strong>Transcriptomic profiling revealed a postpartumspecific interferon signature (STAT1, GBP1), elevated Ki67, and reduced CDKIs; immunofluorescence across > 200 lobules confirmed these increases and suggested that GBP1 fully mediates the STAT1-Ki67 link. In HMECs, knockdown of STAT1 or GBP1 induced a marked rise in p21 and p57 (CDKN1A and CDKN1C), accompanied by G1 cell cycle arrest and reduced proliferation. Combined knockdown had an additive effect on suppressing epithelial proliferation, suggesting a cooperative role for STAT1 and GBP1 in modulating cell cycle progression.</p><p><strong>Conclusions: </strong>These findings identify a STAT1-GBP1 axis that enhances postpartum epithelial proliferation by repressing CDKI expression. This mechanism may help to explain the heightened vulnerability observed after childbirth and highlights potential biomarkers or early intervention targets in postpartum breast tissues.</p>","PeriodicalId":49227,"journal":{"name":"Breast Cancer Research","volume":"27 1","pages":"162"},"PeriodicalIF":5.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12465993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151579","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}