Breast Cancer Research and Treatment最新文献

{"title":"Comparative efficacy of prevention strategies for oral mucositis in breast cancer patients: a network meta-analysis.","authors":"Qianxi Liu, Ruhuai Wang, Siyu Jiang, Jiang Yuan, Guang He, Qian Wang, Shuai Cheng, Lulu Chen, Luyi Zhao, Songjiang Liu","doi":"10.1007/s10549-026-07980-y","DOIUrl":"https://doi.org/10.1007/s10549-026-07980-y","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to evaluate the efficacy of various interventions for preventing and alleviating oral mucositis (OM), a dose-limiting toxicity induced by cancer treatment.</p><p><strong>Methods: </strong>PubMed, Embase, Web of Science, and the Cochrane Library were systematically searched from their inception to March 19, 2026. The quality of included studies was assessed using version 2 of the Cochrane risk-of-bias tool (ROB 2). A Bayesian network meta-analysis (NMA) was conducted utilizing R 4.5.1 and the JAGS package (version 4.3.1). The interventions were compared using league tables, surface under the cumulative ranking curve (SUCRA), and heterogeneity testing.</p><p><strong>Results: </strong>A total of 7,790 articles were retrieved. Ultimately, 10 randomized controlled trials (RCTs) involving 869 patients were included. According to the NMA, zinc most effectively reduced overall OM (RR = 0.53, 95%CrI: 0.27 to 0.95), while propolis dry extract was optimal for grade ≥ 2 OM (RR = 0.15, 95%CrI: 0.01 to 0.99). bifico significantly decreased overall OM (RR = 0.58, 95%CrI: 0.44 to 0.73) and ranked second for grade ≥ 2 OM. Subgroup analyses showed that professional oral health care and zinc were superior in chemotherapy patients, while MuGard and professional oral health care performed best in targeted therapy patients. Professional oral health care was most effective against grade ≥ 2 OM in the targeted therapy subgroup (SUCRA = 96.17%).</p><p><strong>Conclusion: </strong>Zinc and propolis dry extract are the most optimal strategies for overall and grade ≥ 2 OM in BC patients, respectively. bifico shows promising clinical potential. Professional oral health care is effective in both chemotherapy and targeted therapy subgroups. Further large-scale RCTs are needed to validate these findings.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Whole transcriptome analysis reveals MammaPrint and BluePrint-associated gene expression patterns with early lymph node metastasis in early-stage breast cancer.","authors":"Faisal Fa'ak, Josien Haan, Nicole Chmielewski-Stivers, Andrea Menicucci, William Audeh, Phyu Phyu Soe, Zhanna Logman, Soojin Ahn, Nina D'Abreo, Jordan Baum, Douglas K Marks","doi":"10.1007/s10549-026-07982-w","DOIUrl":"https://doi.org/10.1007/s10549-026-07982-w","url":null,"abstract":"<p><strong>Introduction: </strong>Early lymph node (LN) metastasis often precedes systemic metastasis and corresponds with significantly inferior survival for patients diagnosed with early-stage breast cancer (EBC). To understand the biological pathways involved in early LN metastasis, differential gene expression (DGE) analysis compared large tumors without evidence of LN metastasis (pT2-3pN0) to small tumors with LN metastasis (pT1pN+).</p><p><strong>Methods: </strong>This study included 2,349 patients with EBC who underwent MammaPrint and BluePrint testing as part of the FLEX (NCT03053193). DGE was performed between pT2-3pN0/pT1pN + and across their MP/BP subtypes. Immune deconvolution was assessed using gene-signature-based methods, complemented by conventional tumor-infiltrating lymphocyte (TIL) analyses on a representative subset of patients.</p><p><strong>Results: </strong>Greater DGE was observed within the MammaPrint High Risk and BluePrint Luminal B subgroups compared to pathological stages. MammaPrint High Risk tumors saw 73 differentially expressed genes (DEGs), while 34 were found for Luminal B tumors. Gene set enrichment analysis (GSEA) of MammaPrint High Risk/Luminal B tumors showed upregulated proliferation pathways and downregulated epithelial-to-mesenchymal transition (EMT) and immune profiles in pT2-3pN0 vs. pT1pN+, respectively. Immune deconvolution analyses showed a higher abundance of T gamma delta cells and CD4 + Th1 cells and a lower abundance of T regulatory cells, M2 macrophages, and cancer-associated fibroblasts within pT2-3pN0 tumors. Conventional histological assessment revealed no significant differences in TILs.</p><p><strong>Conclusion: </strong>This study lays the groundwork for exploring mechanisms of LN metastasis in EBC and their relation to MammaPrint High Risk and Luminal B subtypes. These data support previous studies' association of LN metastasis with EMT and immune dysregulation.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833474","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Racial differences in pathologic complete response rate and clinical outcomes following neoadjuvant chemotherapy for breast cancer.","authors":"Ashley Matusz-Fisher, Chad A Livasy, Erin E Donahue, Lejla Hadzikadic-Gusic, Ashley Y Martin, Michelle L Wallander, Brittany Neelands, Dhvani Buch, Alicia Griffin, Arielle L Heeke, Antoinette R Tan, Richard L White","doi":"10.1007/s10549-026-07972-y","DOIUrl":"https://doi.org/10.1007/s10549-026-07972-y","url":null,"abstract":"<p><strong>Purpose: </strong>Neoadjuvant chemotherapy (NAC) is commonly used in early-stage breast cancer. A complete pathologic response (pCR) after NAC is associated with improved outcomes. This study investigated differences in pCR and clinical outcomes by race.</p><p><strong>Methods: </strong>A single-institution, retrospective chart review identified patients with early-stage breast cancer who received NAC between January 1, 2010, and December 31, 2017. Associations between race and pathologic and clinical outcomes were evaluated using multivariable logistic regression and Cox proportional hazard models. Kaplan-Meier estimates and log rank tests assessed differences in recurrence-free survival (RFS) and overall survival (OS).</p><p><strong>Results: </strong>A total of 532 patients with breast cancer of all receptor subtypes were identified; 323 (60.7%) White, 188 (35.3%) Black and 21 (3.9%) other/unknown. The pCR rate was different between the 3 race categories; White 27.2%, Black 19.1% and other/unknown 9.5% (P = 0.03). In multivariate analysis, pCR rates were higher in White versus Black patients (P = 0.02). Patients with triple-negative disease demonstrated the largest difference in pCR (White 44.3% versus Black 27.1%; P = 0.04). Black patients had inferior OS compared to White patients (P = 0.03). There was no difference in RFS by race (P = 0.07).</p><p><strong>Conclusion: </strong>Black patients demonstrated a lower pCR rate compared to White patients, and this was more pronounced in the triple-negative subgroup. There was no difference in RFS by race, but OS was inferior among Black patients. It is possible that the lower pCR rate in Black patients may contribute to lower OS; however, more investigation is needed to explain these differences.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144175/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term outcomes in triple-negative breast cancer after a pathologic complete response: does the type of neoadjuvant therapy matter?","authors":"Lis Victória Ravani, Seth A Wander, Marleen Kok, Kelly McCann, Javier Cortes, Romualdo Barroso-Sousa, Maryam Lustberg, José Bines, Isabella Michelon, Laura Testa, Ming Wang, Daxuan Deng, Renata Colombo Bonadio","doi":"10.1007/s10549-026-07963-z","DOIUrl":"https://doi.org/10.1007/s10549-026-07963-z","url":null,"abstract":"<p><strong>Background: </strong>Neoadjuvant chemotherapy is standard for stage IB-III triple-negative breast cancer (TNBC), with pathological complete response (pCR) strongly associated with survival. Although escalation with platinum and immune checkpoint inhibitors (ICI) improves pCR and long-term outcomes, patients with pCR in control arms of pivotal trials also show favorable outcomes. Whether the regimen leading to pCR impacts long-term survival is largely unknown.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis, searching phase II and III trials including early-stage TNBC patients with pCR. A pooled analysis of Kaplan-Meier-derived individual patient data was performed for event-free survival (EFS) and overall survival (OS), with subgroup analyses by treatment regimens.</p><p><strong>Results: </strong>Of 2830 identified publications, 18 trials comprising 3430 patients were included. Neoadjuvant ICI with chemotherapy improved EFS (HR 0.67; 95%CI 0.50-0.89; p < 0.01) compared with chemotherapy-only regimens, with no significant OS difference (HR 0.84; 95%CI 0.50-1.41; P = 0.51). In contrast, EFS and OS were not significantly different regardless of platinum use (HR 0.55; 95%CI 0.20-1.50; P = 0.24 and HR 0.33; 95%CI 0.09-1.22; P = 0.10, respectively). Similarly, anthracycline-containing regimens showed comparable EFS to anthracycline-free regimens (HR 0.86; 95%CI 0.51-1.45; P = 0.58). For patients with pCR after ICI therapy, no benefit of adjuvant ICI for EFS or OS was observed (HR 1.16; 95%CI 0.55-2.44; P = 0.70 and HR 2.91; 95%CI 0.40-21.37; P = 0.29, respectively).</p><p><strong>Conclusion: </strong>These findings suggest that the context in which a pCR is achieved may influence long-term outcomes. Neoadjuvant ICI-based regimens improve EFS in patients with early-stage TNBC and pCR. However, EFS seems not to be impacted by neoadjuvant chemotherapy type.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147833469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative breast cancer screening before chest masculinization surgery.","authors":"Calvin R Schuster, Zohra V Aslami, Claudia Taccheri, Armina Azizi, Diane Saab, Devin Coon, Melissa S Camp, Fan Liang","doi":"10.1007/s10549-026-07967-9","DOIUrl":"https://doi.org/10.1007/s10549-026-07967-9","url":null,"abstract":"<p><strong>Purpose: </strong>Detecting malignancy before gender-affirming chest masculinization surgery (GACMS) can alter surgical planning and prevent reoperation, yet a lack of standardized preoperative breast imaging guidelines has resulted in inconsistent, surgeon-dependent practices and potential missed diagnoses. Limited data evaluating the efficacy of pre-GACMS imaging further contributes to this gap. This study aimed to characterize patterns, indications, and outcomes of preoperative breast imaging before GACMS, and to assess the impact of preoperative imaging on cancer detection, surgical decision-making, and timing to surgery.</p><p><strong>Methods: </strong>A single-institution, retrospective review of adults who underwent GACMS between January 2017-September 2024 was conducted. Descriptive statistics summarize preoperative imaging frequency, indications, modalities, outcomes, and postoperative pathology. Alterations in surgical management based on preoperative versus postoperative cancer detection, as well as an institution-wide screening algorithm, are described.</p><p><strong>Results: </strong>Of 368 patients, 91.8% (n = 338) were under 40 (mean 27.2, range 18-63). Preoperative breast imaging was recommended in 11.7% (n = 43) and performed in 11.1% (n = 41). Modalities included screening mammography (70.7%, n = 29), diagnostic mammography (29.3%, n = 12), MRI (9.8%, n = 4), and ultrasound (7.3%, n = 3). Indications included age (41.9%, n = 18), family history (30.2%, n = 13), physical exam finding (23.3%, n = 10), and BRCA2 mutation (2.3%, n = 1). Imaging revealed irregular findings in 17.1% (n = 7), with malignancy confirmed in 2 patients (4.9% of imaged; 0.5% overall). One patient who did not receive preoperative imaging was found to have invasive ductal carcinoma on postoperative pathology, resulting in 0.8% (n = 3) overall breast cancer diagnoses perioperatively. Preoperative detection altered surgical planning. Median time to surgery did not significantly differ between imaged and non-imaged patients (3.1 vs. 3.7 months, p = 0.2).</p><p><strong>Conclusion: </strong>Preoperative breast cancer imaging before GACMS identified malignancies that significantly influenced surgical planning, preventing additional procedures postoperatively. Implementing a decision-making algorithm could guide and standardize breast imaging before GACMS.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Radiation treatment patterns for breast cancer brain metastases: an NCDB analysis.","authors":"Thamilini Pathmarajah, Yevgeniya Gokun, Nicole Williams, Gina M Sizemore, Heather Lefebvre, Margaret E Gatti-Mays, Brandon Slover, Sierra Daniel, Tanun Jitwatcharakomol, Jacob Eckstein, Therese Andraos, Rebekah Young, John Grecula, Raju Raval, Raj Singh, Simeng Zhu, Dukajin Blakaj, Arnab Chakravarti, Joshua Palmer, Daniel Stover, Sachin R Jhawar, Sasha Beyer","doi":"10.1007/s10549-026-07955-z","DOIUrl":"https://doi.org/10.1007/s10549-026-07955-z","url":null,"abstract":"<p><strong>Purpose: </strong>Breast cancer (BC) brain metastases (BM) treatment involves radiotherapy (RT), surgery, and CNS-penetrating systemic therapies. This study evaluated treatment patterns in brain RT and corresponding survival outcomes among patients with BC BM using the National Cancer Database (NCDB).</p><p><strong>Methods: </strong>Patients diagnosed with BC BM between 2010 and 2021 were identified. RT was categorized as whole brain (WBRT) vs. stereotactic (SRT). We fitted Overlap Propensity Score Weighting (OPSW) Cox models to account for confounders affecting OS. Variables included age, race, ethnicity, Charlson-Deyo score, insurance, molecular subtype, facility type, and systemic therapy.</p><p><strong>Results: </strong>Of 8909 patients with BC BM, 43.4% received brain RT (74.1% WBRT, 25.9% SRT). Patients that are African American, lower income, urban, triple-negative, or at community facilities were more likely to receive WBRT over SRT (p < 0.05). Median OS for the entire cohort was 10.9 months (95% CI 10.4-11.5). Systemic therapy alone (HR 0.40, 95% CI 0.36-0.43) or combined with RT (HR 0.38, 95% CI 0.35-0.42) improved OS; however RT alone did not improve survival on MVA (HR 0.96 (95% CI 0.91-1.02). Among RT recipients, SRT was associated with improved OS vs. WBRT (HR 0.76, 95% CI 0.69-0.83). Older age, comorbidities, lack of insurance, community facilities, and aggressive subtypes were associated with worse OS.</p><p><strong>Conclusions: </strong>Treatment patterns, particularly access to SRT, differ among BC BM patients therefore highlighting the need for strategies to promote equitable implementation of evidence-based guidelines. More prospective trials are also needed to establish evidence-based treatment standards for BC BM.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: mTORC1 is a target of nordihydroguaiaretic acid to prevent breast tumor growth in vitro and in vivo.","authors":"Yue Zhang, Song Xu, Jun Lin, Guangyu Yao, Zelong Han, Bo Liang, Zhenhong Zou, Zhenguo Chen, Qiancheng Song, Yifan Dai, Tianming Gao, Anling Liu, Xiaochun Bai","doi":"10.1007/s10549-026-07918-4","DOIUrl":"https://doi.org/10.1007/s10549-026-07918-4","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oral selective estrogen receptor degraders in hormone receptor-positive, HER2-negative advanced breast cancer: a systematic review and meta-analysis.","authors":"Lorrany Larisse Costa Rodrigues, Lara de Holanda Jucá Silveira, Luiz Felipe C de Almeida, Bianca Gonzaga de Freitas, Valbert Oliveira Costa Filho, Mariana Macambira Noronha, Angela Theresa Zuffo Yabrude, Rodolfo Garza Morales, Andréia Cristina de Melo, Jessé Lopes da Silva, Paolo Tarantino, Felipe Batalini","doi":"10.1007/s10549-026-07962-0","DOIUrl":"https://doi.org/10.1007/s10549-026-07962-0","url":null,"abstract":"<p><strong>Purpose: </strong>The development of endocrine resistance is frequent in hormone receptor-positive, HER2-negative advanced breast cancer (HR + /HER2-ABC), particularly after CDK4/6 inhibitor exposure. Next-generation oral selective estrogen receptor degraders (SERDs) have been developed to improve estrogen receptor blockade; however, randomized trials have yielded heterogeneous results with uncertain clinical benefit.</p><p><strong>Methods: </strong>A PRISMA 2020 compliant systematic review and meta-analysis with PROSPERO registration was conducted. PubMed, Embase, and Cochrane CENTRAL were searched through October 2025 for phase II-III randomized trials comparing oral SERDs with standard endocrine therapy (ET) in HR + /HER2-ABC after prior ET. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR), and treatment-related adverse events (TRAEs). Treatment effects were pooled using random effects models with prespecified subgroup analyses by ESR1 mutation status and key clinical characteristics.</p><p><strong>Results: </strong>Six randomized trials, including 2808 patients, were analyzed. Oral SERDs improved PFS versus standard ET in the overall population (hazard ratio [HR] 0.79; 95% confidence interval [CI] 0.70 to 0.89). ORR was higher with oral SERDs (odds ratio [OR] 1.67; 95% CI 1.23 to 2.28), corresponding to absolute response rates of approximately 21% versus 14%. An OS improvement was observed (HR 0.72; 95% CI 0.57 to 0.90), although follow-up was limited. Benefit was concentrated in ESR1-mutated tumors (PFS, HR 0.57; 95% CI 0.48 to 0.67) with no significant PFS advantage in ESR1 wild-type disease. Gastrointestinal adverse events were more frequent with oral SERDs compared with the control ET.</p><p><strong>Conclusions: </strong>Pooled randomized evidence supports a clinically meaningful benefit of oral SERDs over standard ET after endocrine progression in HR + /HER2-ABC, with the strongest and most consistent efficacy observed in ESR1-mutated disease.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Eliminating breast cancer surgery in exceptional responders: selective omission - not blind omission.","authors":"Helen M Johnson, Marios-Konstantinos Tasoulis, Henry M Kuerer","doi":"10.1007/s10549-026-07974-w","DOIUrl":"https://doi.org/10.1007/s10549-026-07974-w","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo exposure to CXCL12-high CAFs and chronic CXCL12 stimulation in vitro is sufficient to enhance metastasis of ER-positive breast cancer.","authors":"Philip C Miller, Utsav Sharma, JiaXiang Tao, Jun Sun, Kelsie Medina-Saenz, Manuel Picon-Ruiz, Cynthia Morata-Tarifa, Susan M Bare, Joyce M Slingerland, Dorraya El-Ashry, Marc E Lippman","doi":"10.1007/s10549-026-07970-0","DOIUrl":"https://doi.org/10.1007/s10549-026-07970-0","url":null,"abstract":"<p><strong>Purpose: </strong>Cancer-associated fibroblasts (CAFs) play important roles in breast cancer (BC) progression and metastasis. Here we investigated whether CAFs from indolent vs. aggressive BCs differ in gene expression profiles and how they impact metastasis.</p><p><strong>Experimental design: </strong>Genotypic differences in CAF lines from basal-like (CAF23_BAS) and luminal-A BC (CAF19_LA), were compared and effects on CAF-induced phenotypes of estrogen receptor (ER) positive BC models evaluated.</p><p><strong>Results: </strong>Co-injection of MCF7 with CAF23_BAS cells enhanced tumor metastasis in vivo, while CAF19_LA did not. CXCL12 was strongly overexpressed in CAF23_BAS. BC cells isolated from MCF7 + CAF23_BAS tumors were enriched in epithelial-mesenchymal transition (EMT) genes and cancer stem cell (CSC)-like behavior. Chronic CXCL12 exposure in vitro, as may occur in BC with high CXCL12-secreting CAFs, phenocopied CAF23_BAS-enhanced metastasis. Single cell analysis of primary human BC revealed CAFs are the major source of CXCL12 in breast tumors. A high CXCL12-CAF gene expression profile was prognostic of poor BC outcome and was strongly over-represented in CAFs within BC metastases. Finally, gene expression changes induced in MCF7 cells by co-injection with CAF23_BAS in vivo correlated significantly with gene expression differences between normal and malignant epithelial cells in BC containing high CXCL12 CAFs.</p><p><strong>Conclusions: </strong>These findings suggest that CXCL12 overexpressing CAFs can induce gene expression changes in breast cancer that promote breast cancer metastasis, potentially through expansion of the CSC population. Targeting the CAF CXCL12/CXCR4 axis may offer a novel treatment strategy for metastatic breast cancer and warrants further investigation.</p><p><strong>Statement of translational relevance: </strong>Cancer associated fibroblasts (CAF) within the breast tumor microenvironment influence breast cancer behavior. Our study indicates that high CXCL12-expressing CAFs can induce a stable metastatic phenotype in estrogen receptor positive breast cancer models. Gene expression similarities between a high CXCL12 CAF line and high CXCL12-expressing CAFs from primary and metastatic human breast cancers define a CXCL12-high CAF signature that is prognostic of poor BC patient outcome. Furthermore, gene expression changes induced in MCF7 cells by CXCL12 high CAFs in vivo were similar to the gene expression differences between normal and malignant breast epithelial cells in breast cancers containing CXCL12 high CAFs. Disruption of CAF-driven, CXCL12-mediated reprogramming of breast cancer cells might provide an opportunity to prevent or treat breast cancer metastasis.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":"217 2","pages":""},"PeriodicalIF":3.0,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147697611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}