Breast Cancer Research and Treatment最新文献

{"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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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":"https://doi.org/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":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","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":"Improved breast cancer diagnosis using a CA15-3 capture antibody-lectin sandwich assay.","authors":"S Nikseresht, L K Shewell, C J Day, M P Jennings, H Chittoory, A E McCart Reed, P T Simpson, S R Lakhani, R Nabiee, M Moore, R Khanabdali, L M Hinch, G E Rice","doi":"10.1007/s10549-025-07672-z","DOIUrl":"https://doi.org/10.1007/s10549-025-07672-z","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to test the hypothesis that an enzyme-linked antibody-lectin sandwich assay for a glycovariant of CA15-3 can deliver better diagnostic performance, defined by classification accuracy, sensitivity and specificity, for breast cancer compared to an existing FDA-approved CA15-3 test.</p><p><strong>Methods: </strong>A genetically engineered lectin (SubB2M) that specifically binds N-glycolylneuraminic acid (Neu5Gc) was used as a detection reagent in a CA15-3 capture antibody-lectin sandwich (neuCA15-3) assay. In a case: control cohort equivalence study the classification accuracy for the neuCA15-3 assay was determined and compared to an FDA-approved CA15-3 IVD test (Elecsys CA15-3 II, Roche Diagnostics).</p><p><strong>Results: </strong>Classification accuracy and AUC for neuCA15-3 were 81% and 0.886 ± 0.015 (standard error, n = 567) and for Elecsys CA15-3 II, 55% and 0.642 ± 0.023 (n = 558), respectively. At a threshold cut-off serum concentration of 23.6 units/ml, overall breast cancer classification accuracy of the neuCA15-3 was 81% (compared to 55% for the comparator assay, p < 0.001). At 95% specificity, the sensitivity of the neuCA15-3 assay was 69.5%, significantly greater than the comparator assay (11.9%, p < 0.001). neuCA15-3 concentrations did not vary significantly with breast cancer receptor subtype or comorbidities tested.</p><p><strong>Conclusions: </strong>The diagnostic performance of neuCA15-3 was substantially improved by specifically targeting both a CA15-3 protein epitope and a pan-cancer glycan (Neu5Gc) epitope (the specific binding target of SubB2M). The reporter signal generated depends on the colocalization of the cancer antigen protein epitope and the aberrant sialylation of the protein, thus increasing the assay specificity. The presence of multiple Neu5Gc lectin-binding sites per glycoprotein molecule increases signal generation and assay sensitivity. The inclusion of additional cancer biomarkers in a multivariate index assay format may further increase diagnostic performance for breast cancer.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728641","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":"Comment on ''patient preferences for CDK4/6 inhibitor treatments in HR + /HER2- early breast cancer: a discrete choice survey study''.","authors":"Wei Zhang, Shenghong Shi, Ying Hong","doi":"10.1007/s10549-025-07673-y","DOIUrl":"https://doi.org/10.1007/s10549-025-07673-y","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728625","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":"Timing of radiofrequency identification tag placement: can early placement save time and patient experience?","authors":"Ashley M Newman, Abigail E Daly, Kyle J Anderman, Pragya A Dang, Anvy T Nguyen, Barbara L Smith, Michele A Gadd, Michelle C Specht","doi":"10.1007/s10549-025-07681-y","DOIUrl":"https://doi.org/10.1007/s10549-025-07681-y","url":null,"abstract":"<p><strong>Purpose: </strong>Radiofrequency identification tag localization (TL) is a method of localizing nonpalpable breast cancers and high-risk lesions that can be performed prior to the day of surgery (DOS). We evaluated if placement of TL prior to DOS would affect patients' length of stay (LOS) and improve surgical on-time starts.</p><p><strong>Methods: </strong>A retrospective review of excisional biopsies and lumpectomies with TL was performed. Associations between timing of TL (DOS vs. prior), time in radiology, surgical case delay, LOS on DOS, and total LOS were assessed.</p><p><strong>Results: </strong>439 patients underwent TL for nonpalpable breast cancer or high-risk lesions between July 2018 and July 2021 at our institutions. 158 TL procedures were performed on the DOS and 281 TL procedures were performed a median of 3 days prior to the DOS (range 1-28). All intended targets were removed. The median total LOS (time in radiology and surgery) was 336 min and 434 min for the early placement group and DOS group, respectively (p < 0.001). The median length of time in radiology was 47 min for the early placement group and 54 min for the DOS group (p < 0.001). Cases were significantly more likely to be delayed (p = 0.002) and could not be first-start cases if TL was performed on DOS. Vasovagal events during TL and narcotic use in the post-operative setting were rare across both groups.</p><p><strong>Conclusions: </strong>TL prior to DOS was associated with a decrease in total LOS (p < 0.001) and case delay (p = 0.002), as well as an increase in first-start cases. These findings suggest the potential superiority of TL prior to DOS.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143718052","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":"Population attributable risk of a competing-risk model for breast cancer and non-breast cancer death among women ≥ 65 years.","authors":"Mara A Schonberg, Emily A Wolfson, A Heather Eliassen, Bernard A Rosner, Andrea Z LaCroix, Rebecca A Nelson, Rowan T Chlebowski, Long H Ngo","doi":"10.1007/s10549-025-07683-w","DOIUrl":"https://doi.org/10.1007/s10549-025-07683-w","url":null,"abstract":"<p><strong>Purpose: </strong>To inform decision making around mammography-screening frequency and cessation, we previously used Fine-Gray competing-risk regression to develop and validate a model to estimate older women's 10-year risk of breast cancer and their competing risk of non-breast cancer (non-BC) death. Here, we aimed to understand the amount of incident breast cancer and non-BC death risk explained by our model among women ≥ 65y.</p><p><strong>Methods: </strong>We included women ≥ 65y who completed the 2004 Nurses' Health Study questionnaire (NHS, n = 59,662) or who participated in the Women's Health Initiative-Extension Study (WHI-ES, n = 82,528). We calculated our model's full and risk factor-specific population attributable risk (PAR%) for incident breast cancer and non-BC death.</p><p><strong>Results: </strong>Mean age of the NHS participants was 73.5y (SD 5.2); 3.1% were diagnosed with breast cancer and 26.1% experienced non-BC death within 10 years. Mean age of WHI-ES participants was 73.6y (SD 5.4); 4.2% were diagnosed with breast cancer and 17.7% experienced non-BC death within 10 years. The full-model PAR% for breast cancer was 58.8% (22.7-80.6) in NHS and 54.8% (24.8-75.2%) in WHI-ES. Modifiable risk factors explained approximately 1/3 of breast cancer risk; BMI ≥ 30 had a PAR% of 6.5% (3.1-9.9%) in NHS and 12.2% (8.5-16.0%) in WHI-ES. For non-BC death, the full-model PAR% was 94.2% (91.4-96.1%) in NHS and 86.2% (80.9-90.0%) in WHI-ES.</p><p><strong>Conclusions: </strong>Our competing-risk model explained the majority of breast cancers and non-BC deaths in women ≥ 65y, and we identified risk factors (e.g., elevated BMI) that may be targeted to reduce the burden of breast cancer in older women.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699313","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":"Treatment patterns and outcomes in HER2-low metastatic breast cancer patients previously treated with chemotherapy: a US real-world cohort study.","authors":"Shanu Modi, Suyuan Zhang, Danalyn Byng, Shannon Hunter, Alessandria Strübing, Yan Xiong, Kyle Dunton, Zacharie Mbanya, William Jacot","doi":"10.1007/s10549-025-07649-y","DOIUrl":"https://doi.org/10.1007/s10549-025-07649-y","url":null,"abstract":"<p><strong>Purpose: </strong>Real-world outcomes are poorly understood for patients with human epidermal growth factor receptor 2 (HER2)-low (immunohistochemistry 1+ or 2+ with negative in situ hybridization) metastatic breast cancer (mBC).</p><p><strong>Methods: </strong>Using for the first time a nationwide electronic health record-derived de-identified database, we assessed demographics, treatment patterns, and outcomes of patients with HER2-low mBC who previously received one line of chemotherapy in the metastatic setting. The post-chemotherapy line was termed the index line of therapy (LOT).</p><p><strong>Results: </strong>3765 patients [hormone receptor (HR)-positive: 78.8%, HR-negative: 21.0%] met the inclusion criteria (1 January 2011-30 April 2023). 61.7% of HR-positive patients received endocrine therapy prior to the index LOT. The largest patient percentage received single-agent chemotherapy at the index and subsequent two LOTs. For the overall cohort, the median real-world time to treatment discontinuation/death was 4.1 months (95% CI: 3.9-4.2) and the median real-world time to next treatment/death was 5.1 months (95% CI: 4.8-5.3) from the index LOT. Median real-world overall survival (all patients) was 15.8 months (95% confidence interval: 15.2-16.5, median follow-up = 54.5 months) from the index LOT.</p><p><strong>Conclusion: </strong>These data highlight the unmet clinical needs of patients with HER2-low mBC by characterizing the treatment patterns and poor outcomes in this population on the current standard of care.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143708575","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":"Critical appraisal of a data mining model for predicting nodal response to neoadjuvant treatment in breast cancer.","authors":"Janhavi Venkataraman, Kefah Mokbel","doi":"10.1007/s10549-025-07686-7","DOIUrl":"https://doi.org/10.1007/s10549-025-07686-7","url":null,"abstract":"","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143676819","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":"Potential candidates for adjuvant olaparib treatment in operable breast cancer patients with germline BRCA1/2 pathogenic variants after neoadjuvant chemotherapy.","authors":"Huimin Liu, Furong Kou, Li Hu, Jie Sun, Juan Zhang, Ye Xu, Lu Yao, Yuntao Xie","doi":"10.1007/s10549-025-07687-6","DOIUrl":"https://doi.org/10.1007/s10549-025-07687-6","url":null,"abstract":"<p><strong>Background: </strong>Human epidermal growth factor receptor 2 (HER2)-negative operable breast cancer (BC) patients with germline BRCA1/2 pathogenic variants may benefit from adjuvant olaparib treatment. However, data about how many patients were eligible for olaparib treatment in operable BC patients with BRCA1/2 variants after neoadjuvant chemotherapy (NACT) is lacking.</p><p><strong>Methods: </strong>A total of 341 operable BC with germline BRCA1/2 pathogenic variants who received NACT at our institute between October 2003 and May 2015 were included. Pathological complete response (pCR) and survival were estimated.</p><p><strong>Results: </strong>Of the 341 BRCA1/2 carriers (BRCA1: 139; BRCA2: 202), 295 (88.1%) cases exhibited HER2-negative BC in the entire cohort. The most common subtype was triple-negative (TN) BC (62.0%) for BRCA1 carriers and hormone receptor (HR)-positive/HER2-negative BC (68.2%) for BRCA2 carriers, respectively. The pCR rate were 39.6% for BRCA1 carriers and 28.2% for BRCA2 carries. The pCR rate in TNBC, HR-positive/HER2-negative BC, and HER2-positive BC were 45.0%, 22.3%, and 45.0% in the entire cohort, respectively. Of these HR-positive/HER2-negative BC patients, 16.0% had non-pCR and exhibited CPS+EG≥3. Overall, 31.9% of the HER2-negative BC cohort were potential candidates for adjuvant olaparib, with 44.0% for BRCA1 carriers and 22.9% for BRCA2 carriers. Furthermore, patients with non-pCR exhibited a worse survival regardless of TNBC and HR-positive/HER2-negative BC disease, especially for HR-positive/HER2-negative BC with CPS+EG≥3.</p><p><strong>Conclusion: </strong>Approximately one-third of HER2-negative BC patients with BRCA1/2 pathogenic variants are potential candidates for adjuvant olaparib treatment after NACT, with a higher proportion for BRCA1 carriers compared to BRCA2 carriers.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662253","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":"Mitochondrial tRNA fragment, mt-tRF-Tyr-GTA-001 (tRF-21-X3OJI8EWB), in breast cancer and its potential clinical implications.","authors":"Junlong Wang, Dionyssios Katsaros, Zhanwei Wang, Li Ma, Elena Casetta, Peiwen Fei, Pietro Denti, Ida Grimaudo, Shaoqiu Chen, Youping Deng, Herbert Yu","doi":"10.1007/s10549-025-07682-x","DOIUrl":"https://doi.org/10.1007/s10549-025-07682-x","url":null,"abstract":"<p><strong>Background: </strong>Transfer RNA (tRNA) fragments (tRFs) are a group of small non-coding RNAs with biological functions. The involvement of tRNAs in cancer has also been recognized, but most studies focused on nuclear tRFs, very few on mitochondrial tRFs.</p><p><strong>Methods: </strong>We analyzed the TCGA microRNAseq data to identify differentially expressed mitochondrial tRFs (mt-tRFs) in breast tumors and evaluated their associations with the disease outcome. Cox proportional hazards regression was used to determine the associations between mt-tRFs and patient survival while adjusting for clinicopathological variables. Quantitative RT-PCR was developed to measure a specific tRF expression in a validation study.</p><p><strong>Results: </strong>Our analysis of 1,060 tumor samples from TCGA revealed that mt-tRF-Tyr-GTA-001 (tRF-21-X3OJI8EWB or t00018104) expression, a tRF from mitochondrial tRNA with tyrosine anticodon GTA (mt-tRNA-Tyr-GTA), was significantly lower in breast tumors than the adjacent tissues (p< 0.0001). Patients with low expression had significantly higher risk of death (HR = 1.69, p = 0.0018) regardless of their age at diagnosis, disease stage, tumor grade, and hormone receptor status. This survival association was replicated in an independent study where mt-tRF-Tyr-GTA-001 expression was measured with qRT-PCR. Further analysis suggested that the mt-tRF expression was correlated with ribonuclease ANG and RNase 4 known to cleave tRNAs and upregulated under hypoxia. IPA interrogation of the mt-tRF-Tyr-GTA-001 expression signature indicated the inhibitory effects of mt-tRF-Tyr-GTA-001 on malignant transformation, tumor growth, and cell invasion. In silico analysis showed that the binding targets of mt-tRF-Tyr-GTA-001 included several oncogenic transcription factors (E2Fs, CCNE1, FOXM1). We also found the mt-tRF correlated with the abundances of M0 macrophages and resting mast cells, two of the immune cells known for innate immunity.</p><p><strong>Conclusions: </strong>In summary, our study suggests that mt-tRF-Tyr-GTA-001, a mitochondrial tRF, may suppress breast cancer progression through its involvement in regulation of cell phenotype and tumor immunity.</p>","PeriodicalId":9133,"journal":{"name":"Breast Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656042","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}