Breast Cancer Research and Treatment最新文献

{"title":"Severe hyponatremia with abemaciclib use in the absence of pre-existing renal disease.","authors":"Tae Hoon Kim, Amanda Podolski, Eleonora Teplinsky","doi":"10.1007/s10549-025-07739-x","DOIUrl":"10.1007/s10549-025-07739-x","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"435-436"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191517","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":"Mammographic calcifications association with risk of advanced breast cancer.","authors":"Karla Kerlikowske, Linn Abraham, Brian L Sprague, Olivia Sattayapiwat, Sarah J Nyante, Jeffrey A Tice, Diana L Miglioretti","doi":"10.1007/s10549-025-07753-z","DOIUrl":"10.1007/s10549-025-07753-z","url":null,"abstract":"<p><strong>Purpose: </strong>Mammographic calcifications on mammograms with a negative/benign assessment are associated with increased breast cancer risk. Associations with advanced breast cancer risk are unknown. We evaluated whether calcifications recorded on mammography reports are associated with advanced invasive breast cancer risk.</p><p><strong>Methods: </strong>We included 3,710,313 screening mammograms with a negative/benign final assessment performed on 991,991 women aged 40-74 in the Breast Cancer Surveillance Consortium associated with 7229 advanced cancers. We calculated cumulative 5-year advanced (prognostic pathologic stage ≥II) breast cancer risk and hazards ratios (HR) adjusted for clinical risk factors according to presence or absence of calcifications by menopausal status, dense (heterogeneously or extremely dense) vs. non-dense (almost entirely fatty or scattered fibroglandular density) breasts, body mass index (BMI) < 25 kg/m² vs. ≥ 25 kg/m².</p><p><strong>Results: </strong>Prevalence of calcifications was 6.1% among women who developed advanced breast cancer vs. 3.6% among others. Overall associations of advanced cancer with calcifications were similar for premenopausal (HR = 1.4; 95% CI 1.1-1.9) and postmenopausal (HR = 1.5; 95% CI 1.2-1.7) women. Compared to postmenopausal women with non-dense breasts and BMI < 25 kg/m² without calcifications [cumulative 5-year advanced cancer incidence = 1.6 (95% CI 1.3-2.0) per 1000 women], postmenopausal women with dense breasts, BMI ≥ 25 kg/m², and calcifications had 5.5-fold (95% CI 3.9-7.7) higher advanced cancer risk [cumulative 5-year advanced cancer incidence = 10.2; (95% CI 7.0-13.3) per 1000 women]. Results were similar for premenopausal women.</p><p><strong>Conclusion: </strong>Mammographic calcifications increase advanced cancer risk beyond having dense breasts and being overweight/obese. Future research should investigate strength of associations by type of calcification and incorporation of calcifications into advanced cancer risk models for improvement in model accuracy.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"555-567"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209027/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144315897","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":"Adjunctive statistical standardization of quantitated adjuvant HER2 and ultra-low HER2 in Canadian Cancer Trials Group MA.27 trial of exemestane versus anastrozole.","authors":"Judith-Anne W Chapman, Jane Bayani, Sandip SenGupta, John M S Bartlett, Tammy Piper, Mary Anne Quintayo, Shakeel Virk, Paul E Goss, James N Ingle, Matthew J Ellis, George W Sledge, G Thomas Budd, Manuela Rabaglio, Rafat H Ansari, Richard Tozer, David P D'Souza, Haji Chalchal, Silvana Spadafora, Vered Stearns, Edith A Perez, Karen A Gelmon, Timothy J Whelan, Catherine Elliott, Lois E Shepherd, Bingshu E Chen, Karen J Taylor","doi":"10.1007/s10549-025-07749-9","DOIUrl":"10.1007/s10549-025-07749-9","url":null,"abstract":"<p><strong>Purpose: </strong>Statistically standardized estrogen receptor (ER) and progesterone receptor (PgR) differentiated prognosis. Here we examined statistically standardized human epidermal growth receptor 2 (HER2).</p><p><strong>Methods: </strong>CCTG MA.27 (NCT00066573) was an adjuvant phase III trial of exemestane versus anastrozole in postmenopausal women with ER + and/or PgR + tumors. We centrally quantitated machine-image immunohistochemical HER2, defined American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) dual-probe FISH HER2/CEP17 categories, determined ultra-low HER2 (IHC 0 with (0,10%] 1 + stain), and standardized HER2 to mean 0, standard deviation 1. Univariate distant disease-free survival (DDFS) was described with Kaplan-Meier plots and examined with Wilcoxon (Peto-Prentice) test statistic. Adjusted Cox multivariable regressions 2-sided Wald tests had nominal significance p < 0.05.</p><p><strong>Results: </strong>Of 7576 women, 2900 had ER results; 2726, PgR; 2680, HER2; and 2325, ER/PgR/HER2 for multivariable investigations. ASCO/CAP categorization significantly differentiated univariate DDFS (p = 0.01), although not values of IHC 0 (N = 864) and ultra-low HER2 (N = 1143). Statistical standardization did not differentiate univariate DDFS (p = 0.08-0.27); however, (natural logarithm-) standardized values ≤ - 1.0 (ultra-low 1 + /2 + /3 + HSCORE, or % + , < 0.1) were similar to > 1.0 (HSCORE > 19; % +  > 14). Neither ASCO/CAP, nor statistically standardized, ER (p = 0.65-0.94) or HER2 (p = 0.20-0.97) were associated with DDFS in models with PgR; higher PgR had better DDFS (p ≤ .003).</p><p><strong>Conclusions: </strong>ASCO/CAP categories significantly differentiated DDFS, while statistical standardization did not. Patients with ultra-low HER2 and IHC 0 without stain had similar 5-year DDFS, while standardization indicated similar prognosis for very low 1 + /2 + /3 + and highest HER2 stain. We caution about assessment of ultra-low, or very low, HER2 due to HER2 assay dynamic range.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"51-61"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144474021","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":"The deltopectoral lymph node: a potential protective biomarker for breast cancer-related lymphedema.","authors":"James E Fanning, Angela Chen, Sarah Thomson, Elizabeth Tillotson, Aaron Fleishman, John A Parker, Kevin Donohoe, Dhruv Singhal","doi":"10.1007/s10549-025-07748-w","DOIUrl":"10.1007/s10549-025-07748-w","url":null,"abstract":"<p><strong>Background: </strong>The lateral upper arm lymphatic pathway is theorized as a route of superficial lymphatic drainage protective against breast cancer-related lymphedema (BCRL) after axillary lymph node dissection (ALND). This study describes lymph nodes draining the lateral upper arm pathway.</p><p><strong>Methods: </strong>Healthy female volunteers underwent bilateral ICG lymphography and nuclear lymphoscintigraphy. Nuclear tracer was injected over the cephalic vein in the upper arm. Lymph nodes with tracer uptake were recorded as deltopectoral, Station 1 (Axillary Levels I or II and Interpectoral), or Station 2 (Axillary Level III, Infraclavicular, Supraclavicular Levels IV or Vb, and Cervical Level Va).</p><p><strong>Results: </strong>72 arms of 36 volunteers were included. Functional drainage to deltopectoral lymph nodes was observed in 38% (27/72) of arms. Drainage to Station 1, Station 2, and neither station was observed in 96% (69/72), 36% (26/72), and 3% (2/72) of arms, respectively. No differences were observed between arms with or without deltopectoral lymph nodes draining to Station 1 lymph nodes (93% vs 98%, p = 0.286) or neither station (4% vs 2%, p = 0.711), respectively. A significant difference was observed between arms with or without deltopectoral lymph nodes draining to Station 2 lymph nodes (52% vs 27%, p = 0.031).</p><p><strong>Conclusions: </strong>Deltopectoral lymph node drainage is significantly correlated with Station 2 lymph node drainage. As Station 2 lymph nodes are preserved in an ALND, the presence of deltopectoral lymph node drainage represents an important potential protective biomarker for BCRL development.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"43-49"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144494644","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":"Phase I/II trial investigating gedatolisib plus talazoparib in advanced triple negative or BRCA1/2 positive, HER2 negative breast cancers.","authors":"Sneha Phadke, Kathy D Miller, Ami Shah, Oana C Danciu, Yi Chen, Menggang Yu, Mark E Burkard, Kari B Wisinski","doi":"10.1007/s10549-025-07747-x","DOIUrl":"10.1007/s10549-025-07747-x","url":null,"abstract":"<p><strong>Purpose: </strong>Metastatic triple negative breast cancer has a poor prognosis with limited targeted treatment options. In preclinical studies PI3K inhibition led to increased DNA damage and subsequent sensitization to PARP inhibition. This study aimed to investigate the safety and efficacy of the combination of an mTOR/pan-PI3K inhibitor, gedatolisib, with the PARP inhibitor, talazoparib, in patients with advanced triple negative breast cancer or advanced HER2 negative breast cancer and a germline BRCA1/2 mutation.</p><p><strong>Methods: </strong>The primary objective of the safety run-in was safety and tolerability of the combination and for dose escalation to find the maximum tolerated dose. A 3 + 3 design was utilized for dose escalation. The primary objective of the phase II study was objective response rate (ORR) in the patients with wildtype germline BRCA1/2. The prespecified efficacy threshold was 20%. Secondary objectives included progression-free (PFS) and overall survival (OS) as well as correlative testing, examining homologous recombination deficiency (HRD) status.</p><p><strong>Results: </strong>The combination of gedatolisib and talazoparib carried manageable toxicities with a low incidence of grade 3 adverse events. The most common adverse events of all grades were anemia, fatigue, and oral mucositis. The ORR in the phase II study was 12%. There were no new safety signals identified in the phase II study. mPFS was 2.5 months (95% CI 1.71, 9.89), and mOS was 7 months (95% CI 4.3, NA) in the full phase II cohort. HRD status was analyzed by high (≥ 33) or low (< 33) genomic instability score, and there was no difference in response rate between the groups.</p><p><strong>Conclusion: </strong>The combination of gedatolisib and talazoparib is safe but did not meet the prespecified efficacy threshold for objective response rate. Additional preclinical studies of these pathways are warranted prior to future clinical trials of the combination.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov ID: NCT03911973, Date of registration: 2019-04-11.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"521-530"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224254","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":"Promoting resilience in stress management (PRISM) for patients with early stage breast cancer: a pilot feasibility study.","authors":"Gabrielle B Rocque, Etzael Ortiz Olguin, Jessi M Shuey, Tanvi Padalkar, Courtney P Williams, Andres Azuero, Ana Falcao, Nicole L Henderson, Chloe J Taub, Molly Ream, Joyce P Yi-Frazier, Courtney C Junkins, Katherine Reeder-Hayes, Abby R Rosenberg","doi":"10.1007/s10549-025-07741-3","DOIUrl":"10.1007/s10549-025-07741-3","url":null,"abstract":"<p><strong>Purpose: </strong>Women with breast cancer often experience persistent psychological distress. Promoting resilience in stress management (PRISM) is a manualized, skills-based, psychosocial intervention shown to promote resilience and alleviate psychological distress among adolescents and young adults with cancer.</p><p><strong>Methods: </strong>This pilot, convergent mixed methods study examined PRISM's feasibility and in-sample preliminary impact (single-group) on psychosocial outcomes of women with early stage breast cancer (EBC). Women receiving chemotherapy for stage I-III breast cancer completed six standard PRISM sessions focused on rapport building, stress management, goal setting, cognitive reframing, meaning-making, and family integration. Feasibility, the primary outcome, was defined as 70% of participants completing all intervention sessions and pre-post survey. Secondary outcomes included intervention acceptability, appropriateness, and 8 psychosocial outcomes. Patient perspectives on PRISM were elucidated via qualitative interviews and deductively analyze. Pre- and post-intervention changes in survey scores were analyzed using paired t-tests and Cohen's d effect size.</p><p><strong>Results: </strong>Of 57 patients approached, 30 (53%) participated in PRISM; participants were 57% Black with median age of 51 years (IQR 47-59). PRISM sessions were feasible based on the 83% completion rate. Additional secondary implementation outcomes also demonstrated feasibility, acceptability, and appropriateness using validated survey measured. The largest effects were observed in participants' resilience (d = 0.6), growth (d = 0.5), and self-improvement (d = 0.5). Interviews supported both feasibility and impact of PRISM.</p><p><strong>Conclusion: </strong>The PRISM-EBC intervention was feasible, and pre-post changes suggest potential benefit, warranting further investigation in a future randomized controlled trial.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"487-497"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209016/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301142","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":"A mixed-methods study characterizing experiences of medical oncologists' use of gonadotropin-releasing hormone agonists for treatment of breast cancer.","authors":"Kimberley T Lee, Bihe Hu, Dinorah Martinez Tyson, Carley Geiss, Susan T Vadaparampil, Heather S L Jim, Clement K Gwede, Hatem H Soliman, N Lynn Henry, Dawn L Hershman","doi":"10.1007/s10549-025-07734-2","DOIUrl":"10.1007/s10549-025-07734-2","url":null,"abstract":"<p><strong>Purpose: </strong>The use of ovarian function suppression (OFS) for the treatment of breast cancer in pre-menopausal women is low and little is known about medical oncologist' attitudes toward current guidelines pertaining to the use of OFS. This purpose of this study was to explore breast medical oncologists' perceptions and use of gonadotropin-releasing hormone agonists as OFS for treatment of early-stage breast cancer.</p><p><strong>Methods: </strong>A quantitative survey exploring experiences with OFS was distributed to medical oncologists across the USA using mailing lists available through the American Medical Association. Survey responses were characterized using descriptive statistics.</p><p><strong>Results: </strong>Oncologists in this study reported high likelihood of recommending OFS for pre-menopausal women at high risk for recurrence of hormone receptor-positive early-stage breast cancer. In addition to tumor size, nodal involvement, and 21-gene recurrence scores, administration of chemotherapy was a strong surrogate for risk of recurrence. Concerns about treatment toxicity and patient hesitancy were the top barriers to OFS utilization. Oncologists also reported low confidence in their ability to determine menopausal status in the setting of amenorrhea post-chemotherapy (9% reported feeling very confident with this task) and to monitor ovarian function while on OFS.</p><p><strong>Conclusion: </strong>Oncologists reported strong agreement with established guidelines for the use of OFS in the treatment of early-stage hormone receptor-positive breast cancer. However, our findings indicate a need for guidance regarding the determination of menopausal status in the setting of amenorrhea and monitoring of ovarian function.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"449-455"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12209034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214938","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":"Local treatment of ipsilateral breast cancer recurrence: a sensitive decision-making process.","authors":"Jean-Michel Hannoun-Levi, Vratislav Strnad, Csaba Polgar","doi":"10.1007/s10549-025-07761-z","DOIUrl":"10.1007/s10549-025-07761-z","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"577-578"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274227","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":"Analysis of the impact of the COVID-19 pandemic on the stage at diagnosis in breast cancer patients at a French comprehensive cancer centre, through two different methods: a preliminary study.","authors":"Alessandra Zago, Emilie Lévêque, Aline Augustynen, Marianne Leheurteur, Marie Ottaviani, Agnès Loeb, Thomas Vermeulin","doi":"10.1007/s10549-025-07762-y","DOIUrl":"10.1007/s10549-025-07762-y","url":null,"abstract":"<p><strong>Purpose: </strong>In early 2020, the Coronavirus-19 (COVID-19) pandemic led to widespread lockdowns, disrupting cancer-screening programs and limiting access to care. Although a temporary drop in new breast cancer diagnosis had been noted, variations in stage of disease have been explored less frequently, and with methodological approaches that might lead to imprecise or approximative results. This preliminary study aimed to assess possible variations in breast cancer stage at diagnosis over a long-time period using two different approaches.</p><p><strong>Methods: </strong>We analysed data from 3 787 women with invasive breast cancer treated at our comprehensive cancer centre between 2017 and 2022. We evaluated changes in proportions of staging parameters using two different approaches: a traditional \"pre-to-post pandemic\" traditional comparison and time series models. The latter included ARIMA (AutoRegressive Integrated Moving Average) models, complemented by the research of potential significant estimated structural breakpoints over time in linear regression models.</p><p><strong>Results: </strong>The pre-to-post comparison suggested an overall positive overview of the differences observed before and after the pandemic. However, ARIMA and logistic models demonstrated a relative stability in tumour size and metastatic status, with only one significant breakpoint observed: a shift in the rate of patients with no lymph node involvement (N0), likely unrelated to the pandemic.</p><p><strong>Conclusions: </strong>This is the first study to assess changes in breast cancer stage at diagnosis using time series and structural breakpoint analysis over an extended period. Our preliminary results highlight the importance of using advanced statistical techniques when evaluating the impact of systemic disruptions (like COVID-19) on cancer care.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"93-100"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144504847","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":"Tumoral pSMAD2 as a prognostic biomarker in early-stage breast cancer: insights from the randomized SweBCG91RT trial.","authors":"Axel Stenmark Tullberg, Viktoria Thurfjell, Anikó Kovács, Patrick Micke, Aristidis Moustakas, Fredrika Killander, Emma Niméus, Erik Holmberg, Per Karlsson, Carina Strell","doi":"10.1007/s10549-025-07744-0","DOIUrl":"10.1007/s10549-025-07744-0","url":null,"abstract":"<p><strong>Background/aim: </strong>The TGF-β pathway can influence breast cancer progression and therapy efficacy, exhibiting both pro- and anti-tumoral effects. This study examined the impact of active TGF-β signaling on recurrence and radiotherapy (RT) benefit in early-stage breast cancer, using nuclear phosphorylated Smad2 (pSMAD2) as a marker for pathway activation.</p><p><strong>Methods: </strong>Tissue-microarrays from 1178 stage I-IIA breast cancer patients in the SweBCG91RT trial (randomized to breast-conserving surgery with or without RT) were analyzed. pSMAD2 immunohistochemistry was scored as the mean percentage of tumor cells with nuclear staining. Recurrence risk and RT benefit were evaluated.</p><p><strong>Results: </strong>pSMAD2 scores were heavily skewed, with 45% of tumors demonstrating high staining (≥ 80% tumor cells), 38% medium (21-79%), and 17% low (≤ 20%). Low pSMAD2 tumors were associated with higher grade and larger size but not with subtype. Medium pSMAD2 tumors had a significantly increased ipsilateral breast tumor recurrence risk than high pSMAD2 tumors (HR_adjusted = 1.82, p = 0.002), while no differences were observed for low pSMAD2 tumors. A similar result was obtained with all recurrences as endpoint. RT benefit was consistent across all pSMAD2 groups. In Luminal tumors, higher tumoral pSMAD2 levels were inversely correlated with tumor-infiltrating lymphocytes (TILs).</p><p><strong>Conclusion: </strong>Medium pSMAD2 levels were linked to an increased recurrence risk compared to high levels, suggesting a tumor-suppressive role of TGF-β in early breast tumorigenesis. However, no significant differences were noted for low pSMAD2 levels. In Luminal tumors, TGF-β signaling was negatively associated with TILs. These findings indicate that therapeutic targeting of TGF-β warrants careful consideration of tumor stage and subtype.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"499-509"},"PeriodicalIF":3.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12208964/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246429","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}