Breast Cancer Research and Treatment最新文献

{"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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Continuous glucose monitoring to characterize hyperglycemia during chemotherapy for early stage breast cancer.","authors":"Sophie R Ulene, Shikun Wang, Joshua R Cook, Fiona McAuley, Margaux E Wooster, Khadija F Faheem, Andrew Varoli, Julia E McGuinness, Neil Vasan, Meghna S Trivedi, Katherine D Crew, Erik Harden, Cynthia Law, Dawn L Hershman, Melissa K Accordino","doi":"10.1007/s10549-025-07745-z","DOIUrl":"https://doi.org/10.1007/s10549-025-07745-z","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetes (DM) and hyperglycemia during chemotherapy increase the risk of toxicity, yet the prevalence and patterns of hyperglycemia in early-stage breast cancer (ESBC) patients undergoing chemotherapy with concurrent dexamethasone remain poorly understood.</p><p><strong>Methods: </strong>We conducted a prospective single-arm study using FreeStyle Libre Pro continuous glucose monitoring in patients with ESBC receiving chemotherapy from 12/2020-2/2022. Sensors measured interstitial glucose every 15 min and were reapplied every 2-3 weeks. Primary endpoints were (1) prevalence of hyperglycemia (≥ 1 reading ≥ 140 mg/dL), and (2) for those with hyperglycemia, the proportion of time spent hyperglycemic. Secondary endpoints included baseline glucose tolerance by A1c, changes in glucose-related biomarkers, and changes in patient-reported neuropathy, quality of life, and fatigue. Analysis was stratified by baseline A1c (euglycemic < 5.7%, prediabetes [pre-DM] 5.7-6.4%, diabetes [DM] ≥ 6.5%).</p><p><strong>Results: </strong>Among 20 evaluable patients (median age: 60, BMI: 29.5 kg/m²), common chemotherapy regimens included docetaxel/cyclophosphamide (25%), paclitaxel/trastuzumab (20%), paclitaxel then doxorubicin/cyclophosphamide (15%), docetaxel/carboplatin/trastuzumab/pertuzumab (15%), and cyclophosphamide/methotrexate/fluorouracil (15%). All patients received Dexamethasone. At baseline, 10 patients were euglycemic, 7 had pre-DM, and 3 had DM. All experienced hyperglycemia. Of 124,165 total glucose readings, 17% were ≥ 140 mg/dL. By cohort, the proportion of time spent hyperglycemic was 3.9% (euglycemic), 10% (pre-DM), and 73.3% (DM) (p < .0001). Mean glucose values were 95.5 mg/dL (euglycemic), 104.5 mg/dL (pre-DM), and 183.0 mg/dL (DM) (p < .0001).</p><p><strong>Conclusion: </strong>All patients receiving chemotherapy for ESBC experienced hyperglycemia, with time spent hyperglycemic varying significantly by baseline A1c. Future research should explore approaches to and benefits of improving glycemic control during treatment in patients with baseline dysglycemia.</p><p><strong>Trial registration: </strong>NCT04473378.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224253","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":"Insurer and patient costs for repeat breast surgery after initial lumpectomy for breast cancer.","authors":"Sam E Wing, Yuki Liu, Feibi Zheng, Naomi C Hamm, Nayana S Dekhne, Jesse C Selber","doi":"10.1007/s10549-025-07735-1","DOIUrl":"https://doi.org/10.1007/s10549-025-07735-1","url":null,"abstract":"<p><strong>Purpose: </strong> ~ 14-25% of patients who undergo a primary lumpectomy for the treatment of breast cancer require a reoperation due to adverse outcomes like positive surgical margins or early cancer recurrence, adding burden to the patients, providers, and payors. We analyze the economic impact of patients who require repeat breast tissue resection as part of their treatment following initial resection.</p><p><strong>Methods: </strong>We utilized the Merative™ MarketScan Research Database to identify a cohort of women in the United States who received an index lumpectomy between 2016 and 2021 and identified their healthcare encounters one year postoperatively, including any repeat lumpectomies or mastectomies, as well as the use of any intraoperative adjuncts (e.g. localization methods or frozen sections).</p><p><strong>Results: </strong>Among 8,869 patients with a primary lumpectomy, 25% (n = 2197) underwent a second surgery, of which 75% (n = 1644) was a repeat lumpectomy and 25% (n = 553) was a mastectomy. Median healthcare expenditure for primary lumpectomy plus one year follow up was $55,985 USD ($2,500 out-of-pocket). Among patients with secondary procedures, median healthcare expenditure from primary lumpectomy plus one year follow up was $63,416 ($3,005 out-of-pocket) for repeat lumpectomy and $87,961 ($3,100 out-of-pocket) for subsequent mastectomy patients. Repeat procedures were more common among patients who did not receive an intraoperative adjunct for lesion localization or margin assessment.</p><p><strong>Conclusion: </strong>While lumpectomy is the most common surgery for early-stage breast cancer, it often is not definitive, which can result in large added financial and operational burdens. Patient risk stratification and intraoperative adjuncts are needed to minimize risk of reoperation.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207640","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":"National trends in neoadjuvant systemic therapy utilization in patients with early-stage HER2-positive breast cancer from 2016-2021: The impact of the KATHERINE trial.","authors":"Lauren N Cohen, Christine C Rogers, Jan Irene C Lloren, Sailaja Kamaraju, Lubna N Chaudhary, Chiang-Ching Huang, Adrienne N Cobb, Puneet Singh, Amanda L Kong, Mediget Teshome, Chandler S Cortina","doi":"10.1007/s10549-025-07750-2","DOIUrl":"https://doi.org/10.1007/s10549-025-07750-2","url":null,"abstract":"<p><strong>Purpose: </strong>Neoadjuvant systemic therapy (NST) for HER2 + breast cancer (HER2 + BC) has historically been used to downstage disease to facilitate surgical de-escalation; however, in 2019, the KATHERINE trial identified a survival benefit to adjuvant T-DM1 for those with residual disease after NST. We aimed to determine national rates of NST for patients with cT1-2 N0 M0 HER2 + BC and identify factors associated with receipt of NST vs upfront surgery with adjuvant systemic therapy (US-AST).</p><p><strong>Methods: </strong>A retrospective cohort study of women with cT1-2 N0 M0 HER2 + BC was performed using the National Cancer Database from 2016-2021. ANOVA, Kruskal-Wallis, Chi-square, Fisher's Exact tests, and a multivariable logistic regression analysis were used.</p><p><strong>Results: </strong>54,449 patients met inclusion: 30,546 (56.1%) received US-AST and 19,562 (35.9%) received NST. NST utilization increased from 31.1% in 2016-17 to 43.3% in 2020-21. On regression analysis, women diagnosed in 2020-21 were more likely to receive NST (OR 1.9, 95% CI 1.8-2.0). Populations less likely to receive NST included NH-Black women (OR 0.87, 95% CI 0.8-0.95), age ≥ 70 (OR 0.7, 95% CI 0.6-0.8), increasing comorbidities (OR 0.7, 95% CI 0.5-0.9), and Medicare insurance (OR 0.8, 95% CI 0.7-0.8). Patients with cT2 disease were more likely to receive NST vs those with cT1 disease (p < 0.001).</p><p><strong>Conclusion: </strong>From 2016-2021, national rates of NST for patients with cT1-2 N0 HER2 + BC significantly increased. Race/ethnicity and insurance type were associated with receipt of NST underscoring ongoing disparities in care. Future studies are needed to determine the impact of the disparate rates of NST utilization on oncologic outcomes, given the survival benefit with adjuvant T-DM1 in those with residual disease after NST.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144207641","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":"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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of adding palbociclib on treatment adherence to ongoing adjuvant endocrine treatment in the global randomized PALLAS randomized trial in patients with early breast cancer.","authors":"Eileen Shinn, David Zahrieh, Angela DeMichele, Nick Zdenkowski, Julie Lemieux, Jun Mao, Vesna Bjelic-Radisic, Michelle J Naughton, Georg Pfeiler, Karen Gelmon, Justin M Balko, Daniel Egle, Gabriele Zoppoli, Tiffany Traina, Miguel Martin Jimenez, Silvia Antolin Novoa, Tufia Haddad, Arlene Chan, Alistair Ring, Antonio Wolff, William Fraser Symmans, Jose Ponce Lorenzo, Dhanusha Sabanathan, Hal J Burstein, Zbigniew Ireneusz Nowecki, Gunda Pristauz-Telsnigg, Adam Brufsky, Meritxell Bellet-Ezquerra, Theodoros Foukakis, Yelena Novik, Gabor Rubovszky, Christian F Singer, Karoline Muehlbacher, Otto Metzger Filho, Theodora Goulioti, Ernest Law, Ann H Partridge, Lisa A Carey, Alex Zoroufy, Dominik Hlauschek, Christian Fesl, Erica L Mayer, Michael Gnant","doi":"10.1007/s10549-025-07653-2","DOIUrl":"10.1007/s10549-025-07653-2","url":null,"abstract":"<p><strong>Purpose: </strong>Using patient-reported outcomes (PROs) and more objective measures, we evaluated adherence to adjuvant palbociclib and ET in the PALLAS trial, and the impact of palbociclib on ET adherence.</p><p><strong>Methods: </strong>The open-label, global, phase 3 PALLAS trial randomized patients with hormone receptor-positive (HR+), HER2-negative stage II-III breast cancer (1:1) to either 26 cycles of palbociclib (125 mg/day for 21 days and then 7 days off) plus adjuvant ET, versus ET alone. After 23.7 months median follow-up, palbociclib was stopped due to futility of the intervention and patients were moved to follow-up. For each cycle, daily adherence to ET was measured with study diaries; for palbociclib, study diaries and pill counts. At cycles 2, 3, 6, 12, 18 and 24, patients completed the Morisky Medication Adherence Scale-4 plus an additional item and the McHorney Adherence Questionnaire. Mean persistence was defined in months from treatment initiation to cessation.</p><p><strong>Results: </strong>Four thousand six hundred eighty-eight of 5796 total PALLAS participants were included. Across all cycles, mean daily ET adherence values measured by study diary were > 98.0% and did not differ between treatment arms. Mean persistence to ET was similar between arms (19.2 months for palbociclib + ET vs. 19.6 months for ET alone). However, patient-reported maximal ET adherence was higher across time for palbociclib + ET compared to ET alone (p ≤ 0.0001, modified MMAS-4; p = 0.05, McHorney).</p><p><strong>Conclusion: </strong>In the PALLAS trial, addition of palbociclib did not decrease adherence to adjuvant ET. Though numbers declined over time, daily adherence for palbociclib and ET remained relatively high at each cycle.</p><p><strong>Trial registration: </strong>The trial is registered with ClinicalTrials.gov (NCT02513394; 07-31-2015) and EudraCT (2014-005181-30).</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"385-397"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718049","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 density as a predictor of invasive breast cancer and ductal carcinoma in situ in over six million South Korean women.","authors":"Sung Hun Kim, Ga Eun Park, Kimberly A Bertrand, Dale P Sandler, Kyungdo Han, Yong-Moon Mark Park","doi":"10.1007/s10549-025-07648-z","DOIUrl":"10.1007/s10549-025-07648-z","url":null,"abstract":"<p><strong>Purpose: </strong>Evidence on the associations between categorical mammographic density and breast cancer risk by tumor invasiveness remains limited in Asian women. This large, population-based cohort study investigated the distribution of mammographic density by age and menopausal status, as well as its association with the risks of invasive breast cancer and ductal carcinoma in situ (DCIS) in South Korean women.</p><p><strong>Methods: </strong>Mammographic screening was performed on 6,365,522 women between 2009 and 2014 through the Korean National Cancer Screening Program. Mammographic parenchymal composition was classified using the fourth edition of Breast Imaging Reporting and Data System. We computed multivariable-adjusted hazard ratios and 95% confidence intervals (CIs) using Cox proportional hazards regression models for the association between mammographic parenchymal composition and the risk of invasive cancer and DCIS.</p><p><strong>Results: </strong>Overall, 40.6% of women had dense breasts, with the proportion decreasing with increasing age. A total of 44,468 incident breast cancer cases (0.7%) were documented. Compared with almost entirely fatty breasts, increasing mammographic density was associated with a higher risk of breast cancer (HR, 1.55; 95% CI 1.51-1.60 for scattered fibroglandular densities; HR, 2.14; 95% CI 2.08-2.21 for heterogeneously dense breasts; and HR, 2.59; 95% CI 2.50-2.69 for extremely dense breasts). Associations between mammographic density and breast cancer risk were similar for invasive cancer and DCIS, and did not vary significantly by menopausal status.</p><p><strong>Conclusions: </strong>Mammographic density may be a significant risk factor for both invasive cancer and DCIS, regardless of menopausal status. It should be incorporated into breast cancer risk stratification and screening strategies.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"341-350"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143522709","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":"Examining factors associated with experiencing cardiac arrhythmias in Black and White breast cancer survivors who received anthracyclines or trastuzumab.","authors":"Arnethea L Sutton, Jinlei Zhao, Jian He, Katherine Y Tossas, Wendy Bottinor, Vanessa B Sheppard","doi":"10.1007/s10549-025-07671-0","DOIUrl":"10.1007/s10549-025-07671-0","url":null,"abstract":"<p><strong>Purpose: </strong>Racial disparities exist regarding cardiovascular (CV) toxicities following breast cancer treatment; however, studies on racial differences in cardiac arrhythmias are lacking. This study examined associations between demographic and clinical factors and arrhythmia diagnosis in Black and White breast cancer survivors.</p><p><strong>Methods: </strong>This study included a retrospective cohort of Black and White women who were diagnosed with breast cancer and who received potentially cardiotoxic treatment. Cardiac arrhythmia data were captured via International Classification of Diseases, Tenth and Ninth Versions (ICD-10 and ICD-9). Experiences with cardiac arrhythmias were compared across racial groups. The associations of demographic and clinical factors with cardiac arrhythmias were evaluated using logistic regression for all women and in race-stratified models.</p><p><strong>Results: </strong>Thirty-three percent of the total 860 women in our study sample (mean (standard deviation) age 50.3 (10.7) years) old) experienced cardiac arrhythmias. In bivariate analyses, we observed a statistically discernible association between race and arrhythmia status following a breast cancer diagnosis (p = 0.004); however, this association was no longer significant in the multivariable model. In race-stratified multivariable analysis, the odds of experiencing arrhythmias in Black women over 50 years old are 51% lower than in Black women aged 50 years old or younger (adjusted odds ratio (OR): 0.49; 95% confidence interval (CI): 0.28, 0.86). All else being equal, Black women with hypertension had 2.68 times (95% CI: 1.51, 4.81) higher odds of experiencing arrhythmias than those without hypertension. White women with obesity had higher odds of experiencing arrhythmias than those with normal weight or underweight status. (adjusted OR 1.93: [1.17, 3.20]).</p><p><strong>Conclusion: </strong>Survivors with chronic conditions like hypertension and obesity may require enhanced cardiac surveillance. Further investigation into hypertension management in Black survivors may shed light on its impact on CV toxicities in this group.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"537-544"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718044","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":"IGF1R activates FOXP3-β-catenin signaling to promote breast cancer development.","authors":"Lu Li, Zhiming Zhang, Na Huang, Jianlan Ren, Yuan Qin, Yangkun Luo","doi":"10.1007/s10549-025-07663-0","DOIUrl":"10.1007/s10549-025-07663-0","url":null,"abstract":"<p><strong>Purpose: </strong>Forkhead box P3 (FOXP3), a key marker of regulatory T cells (Tregs), is crucial for Treg differentiation and development. Emerging evidence suggests that FOXP3 is also expressed in various tumor cells; however, its role in tumor progression remains controversial. This study aimed to elucidate the impact of FOXP3 on breast cancer development.</p><p><strong>Methods: </strong>Breast cancer cell lines, including HCC1937, HCC1806, Hs 578T, MDA-MB-231, and MCF-7, along with xenograft mouse models, to assess the effects of FOXP3 on cell proliferation and tumor growth. FOXP3 expression in human breast cancer samples was analyzed using quantitative PCR and immunohistochemistry analyses. Cell proliferation and invasion were evaluated through MTS and transwell assays, respectively. Chromatin immunoprecipitation (ChIP) assays were performed to determine FOXP3 binding to the β-catenin gene promoter.</p><p><strong>Results: </strong>FOXP3 expression was elevated in advanced breast cancer and correlates with poor clinical outcomes. FOXP3 directly binds to β-catenin gene promoter - 986 to - 1168 region to facilitate β-catenin transcription, consequently resulting in increased breast cancer cell proliferation, migration, and invasion in vitro and tumor growth in vivo. Furthermore, IGF1R activated FOXP3-β-catenin signaling to promote breast tumor growth. Moreover, elesclomol, a potent copper ionophore, significantly inhibited FOXP3 expression to suppress breast tumor growth.</p><p><strong>Conclusion: </strong>This study indicates that FOXP3 plays an oncogenic role in breast cancer development and suggests that targeting IGF1R-FOXP3-β-catenin signaling may be a putative therapeutic strategy for human breast cancer treatment.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"467-478"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584611","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":"Long-term outcomes of volume de-escalation for breast nodal irradiation.","authors":"Riccardo Ray Colciago, Federica Ferrario, Chiara Chissotti, Giulia Rossano, Lorenzo De Sanctis, Valeria Faccenda, Denis Panizza, Sara Trivellato, Stefano Arcangeli","doi":"10.1007/s10549-025-07652-3","DOIUrl":"10.1007/s10549-025-07652-3","url":null,"abstract":"<p><strong>Introduction: </strong>NCCN recommendations suggest irradiating chest wall/breast only + regional node irradiation (RNI) of the undissected axillary levels for node-positive breast cancer (BC) patients. We retrospectively analyzed a cohort of node-positive BC patients who received adjuvant radiotherapy (RT) with a volume de-escalation at the level of axillary nodes.</p><p><strong>Material and methods: </strong>We conducted a retrospective analysis of node-positive BC patients treated with adjuvant RT administered following a conventional fractionation schedule using a 3D-conformal technique to the chest wall or breast and only the IV axillary level. The primary endpoint of the study was disease free survival (DFS). Secondary endpoints included loco-regional control (LRC), and Overall Survival (OS). Toxicity was documented according to the Radiation Therapy Oncology Group (RTOG) criteria.</p><p><strong>Results: </strong>A total cohort of 343 patients was analyzed. Loco-regional recurrence occurred in 100 (29.1%). The 5- and 10-year Kaplan-Meyer curves for DFS were 81.4% (95% CI: 79.3%-83.5%) and 60.9% (95% CI: 57.6%-64.5%), respectively. Multivariate Cox analysis confirmed that lymph node ratio (HR = 9.76, 95% CI: 3.12-30.53, p = 0.0001), Luminal B subtype (HR = 2.03, 95% CI: 1.26-3.29, p = 0.004), and triple-negative subtype (HR = 2.70, 95% CI: 1.22-5.99, p = 0.01) were significant predictors of poor DFS. Lymphedema in the ipsilateral arm was reported in 32 (9.3%) patients, primarily Grade 1 or 2.</p><p><strong>Conclusions: </strong>Improved patients' selection and a broader use of systemic therapy could make de-escalation a feasible option. However, this approach should be avoided in patients with extensive nodal involvement, specific molecular subtypes, or comorbidities that prevent the use of chemotherapy.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":"375-384"},"PeriodicalIF":3.0,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006277/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482152","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}