Breast Cancer Research最新文献

{"title":"Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA","authors":"Pan Hu, Peiyi Zhou, Tieyun Sun, Dingkang Liu, Jun Yin, Lubin Liu","doi":"10.1186/s13058-023-01749-7","DOIUrl":"https://doi.org/10.1186/s13058-023-01749-7","url":null,"abstract":"Triple-negative breast cancer (TNBC) represents the most challenging subtype of breast cancer. Studies have implicated an upregulation of lipid synthesis pathways in the initiation and progression of TNBC. Targeting lipid synthesis pathways may be a promising therapeutic strategy for TNBC. Our previous study developed a therapeutic protein PAK with passive targeting and inhibiting tumor proliferation. In this study, we further substantiate the efficacy of PAK in TNBC. Transcriptome sequencing analysis revealed PAK-mediated downregulation of genes involved in fatty acid synthesis, including key genes like SREBP-1, FASN, and SCD1. RNA immunoprecipitation experiments demonstrated a significant binding affinity of PAK to SREBP-1 mRNA, facilitating its degradation process. Both in vitro and in vivo models, PAK hampered TNBC progression by downregulating lipid synthesis pathways. In conclusion, this study emphasizes that PAK inhibits the progression of TNBC by binding to and degrading SREBP-1 mRNA, revealing a new strategy for regulating lipid synthesis in the intervention of TNBC and its therapeutic significance.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"74 2 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138566637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study","authors":"Naomie Olivos, Jim E. Banta, Rhonda Spencer-Hwang, Daniel Ansong, Laura E. Beane Freeman, Joe-Nat Clegg-Lamptey, Beatrice Wiafe-Addai, Lawrence Edusei, Ernest Adjei, Nicholas Titiloye, Florence Dedey, Francis Aitpillah, Joseph Oppong, Verna Vanderpuye, Ernest Osei-Bonsu, Thomas U. Ahearn, Richard Biritwum, Joel Yarney, Baffour Awuah, Kofi Nyarko, Montserrat Garcia-Closas, Mustapha Abubakar, Louise A. Brinton, Jonine D. Figueroa, Seth Wiafe","doi":"10.1186/s13058-023-01737-x","DOIUrl":"https://doi.org/10.1186/s13058-023-01737-x","url":null,"abstract":"Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (ORadj) and 95% confidence intervals (CI) with breast cancer risk-adjusted for potential confounders and known risk factors. Among controls, the reported use of mosquito control products were mosquito coils (65%), followed by insecticide-treated nets (56%), repellent room sprays (53%), and repellent skin creams (15%). Compared to a referent group of participants unexposed to mosquito control products, there was no significant association between breast cancer risk and mosquito coils. There was an association in breast cancer risk with reported use of insecticide-treated nets; however, that association was weak and not statistically significant. Participants who reported using repellent sprays were at elevated risks compared to women who did not use any mosquito control products, even after adjustment for all other mosquito control products (OR = 1.42, 95% CI=1.15–1.75). We had limited power to detect an association with repellent skin creams. Although only a few participants reported using repellent room sprays weekly/daily or < month-monthly, no trends were evident with increased frequency of use of repellent sprays, and there was no statistical evidence of heterogeneity by estrogen receptor (ER) status (p-het > 0.25). Our analysis was limited when determining if an association existed with repellent skin creams; therefore, we cannot conclude an association. We found limited evidence of risk associations with widely used mosquito coils and insecticide-treated nets, which are reassuring given their importance for malaria prevention. Our findings regarding specific breast cancer risk associations, specifically those observed between repellent sprays, require further study.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"231 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138569688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular subtypes of breast cancer predicting clinical benefits of radiotherapy after breast-conserving surgery: a propensity-score-matched cohort study","authors":"Shih-Kai Hung, Hsuan-Ju Yang, Moon-Sing Lee, Dai-Wei Liu, Liang-Cheng Chen, Chia-Hui Chew, Chun-Hung Lin, Cheng-Hung Lee, Szu-Chin Li, Chung-Lin Hong, Chih-Chia Yu, Ben-Hui Yu, Feng-Chun Hsu, Wen-Yen Chiou, Hon-Yi Lin","doi":"10.1186/s13058-023-01747-9","DOIUrl":"https://doi.org/10.1186/s13058-023-01747-9","url":null,"abstract":"Based on the molecular expression of cancer cells, molecular subtypes of breast cancer have been applied to classify patients for predicting clinical outcomes and prognosis. However, further evidence is needed regarding the influence of molecular subtypes on the efficacy of radiotherapy (RT) after breast-conserving surgery (BCS), particularly in a population-based context. Hence, the present study employed a propensity-score-matched cohort design to investigate the potential role of molecular subtypes in stratifying patient outcomes for post-BCS RT and to identify the specific clinical benefits that may emerge. From 2006 to 2019, the present study included 59,502 breast cancer patients who underwent BCS from the Taiwan National Health Insurance Research Database. Propensity scores were utilized to match confounding variables between patients with and without RT within each subtype of breast cancer, namely luminal A, luminal B/HER2-negative, luminal B/HER2-positive, basal-like, and HER2-enriched ones. Several clinical outcomes were assessed, in terms of local recurrence (LR), regional recurrence (RR), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). After post-BCS RT, patients with luminal A and luminal B/HER2-positive breast cancers exhibited a decrease in LR (adjusted hazard ratio [aHR] = 0.18, p < 0.0001; and, 0.24, p = 0.0049, respectively). Furthermore, reduced RR and improved DFS were observed in patients with luminal A (aHR = 0.15, p = 0.0004; and 0.29, p < 0.0001), luminal B/HER2-negative (aHR = 0.06, p = 0.0093; and, 0.46, p = 0.028), and luminal B/HER2-positive (aHR = 0.14, p = 0.01; and, 0.38, p < 0.0001) breast cancers. Notably, OS benefits were found in patients with luminal A (aHR = 0.62, p = 0.002), luminal B/HER2-negative (aHR = 0.30, p < 0.0001), basal-like (aHR = 0.40, p < 0.0001), and HER2-enriched (aHR = 0.50, p = 0.03), but not luminal B/HER2-positive diseases. Remarkably, when considering DM, luminal A patients who received RT demonstrated a lower cumulative incidence of DM than those without RT (p = 0.02). In patients with luminal A breast cancer who undergo BCS, RT could decrease the likelihood of tumor metastasis. After RT, the tumor’s hormone receptor status may predict tumor control regarding LR, RR, and DFS. Besides, the HER2 status of luminal breast cancer patients may serve as an additional predictor of OS after post-BCS RT. However, further prospective studies are required to validate these findings.","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"20 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2023-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138552670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway.","authors":"Peh Joo Ho, Alexis Jiaying Khng, Benita Kiat-Tee Tan, Geok Hoon Lim, Su-Ming Tan, Veronique Kiak Mien Tan, Ryan Shea Ying Cong Tan, Elaine Hsuen Lim, Philip Tsau-Choong Iau, Ying Jia Chew, Yi Ying Lim, Mikael Hartman, Ern Yu Tan, Jingmei Li","doi":"10.1186/s13058-023-01730-4","DOIUrl":"10.1186/s13058-023-01730-4","url":null,"abstract":"<p><strong>Background: </strong>Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients.</p><p><strong>Methods: </strong>We performed DNAm analysis in 125 breast cancer patients with blood drawn before and after chemotherapy, using the Illumina MethylationEPIC array. DNAm changes of 588,798 individual CpGs (including 41,207 promoter regions) were evaluated using linear regression models adjusted for monocyte proportion. Gene set enrichment analyses (GSEA) were conducted to identify key Gene Ontology (GO) biological processes or Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with chemotherapy. Results were validated in a separate cohort of breast cancer patients who were treated (n = 1273) and not treated (n = 872) by chemotherapy (1808 blood, 337 saliva).</p><p><strong>Results: </strong>A total of 141 differentially methylated CpGs and 11 promoters were significantly associated with chemotherapy after multiple testing corrections in both the paired sample and single time point analyses. GSEA of promoter regions (pre-ranked by test statistics) identified six suppressed biological processes (p < 4.67e-8) related to sensory perception and detection of chemical stimuli, including smell perception (GO:0007606, GO:0007608, GO:0009593, GO:0050906, GO:0050907, and GO:0050911). The same six biological processes were significantly suppressed in the validation dataset (p < 9.02e-14). The KEGG pathway olfactory transduction (hsa04740) was also found to be significantly suppressed (p_{paired-samples} = 1.72e-9, p_{single-timepoint-blood} = 2.03e-15 and p_{single-timepoint-saliva} = 7.52e-56).</p><p><strong>Conclusion: </strong>The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.</p>","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"25 1","pages":"136"},"PeriodicalIF":7.4,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10626732/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478215","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the interface zone in breast cancer: implications for surgical strategies and beyond.","authors":"Kefah Mokbel,&nbsp;Munaser Alamoodi","doi":"10.1186/s13058-023-01734-0","DOIUrl":"https://doi.org/10.1186/s13058-023-01734-0","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"25 1","pages":"135"},"PeriodicalIF":7.4,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625299/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer.","authors":"Ji Eun Choi,&nbsp;Jae Seok Lee,&nbsp;Min-Sun Jin,&nbsp;Ilias P Nikas,&nbsp;Kwangsoo Kim,&nbsp;Sunah Yang,&nbsp;Soo Young Park,&nbsp;Jiwon Koh,&nbsp;Sohyeon Yang,&nbsp;Seock-Ah Im,&nbsp;Han Suk Ryu","doi":"10.1186/s13058-023-01710-8","DOIUrl":"https://doi.org/10.1186/s13058-023-01710-8","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC).</p><p><strong>Methods: </strong>The expression of eight immune markers (PD-1, PD-L1, PD-L2, IDO, TIM3, OX40, OX40L, and H7-H2) was assessed with immunohistochemistry on the tumor cells (TCs) and immune cells (ICs) of 227 TNBC cases, respectively, and subsequently associated with selected clinicopathological parameters and survival. Data retrieved from The Cancer Genome Atlas (TCGA) were further examined to validate our findings.</p><p><strong>Results: </strong>All immune markers were often expressed in TCs and ICs, except for PD-1 which was not expressed in TCs. In ICs, the expression of all immune markers was positively correlated between one another, except between PD-L1 and OX40, also TIM3 and OX40. In ICs, PD-1, PD-L1, and OX40L positive expression was associated with a longer progression-free survival (PFS; p = 0.040, p = 0.020, and p = 0.020, respectively). In TCs, OX40 positive expression was associated with a shorter PFS (p = 0.025). Subsequently, the TNBC patients were classified into high and low combined immune score groups (CIS-H and CIS-L), based on the expression levels of a selection of biomarkers in TCs (TCIS-H or TCIS-L) and ICs (ICIS-H or ICIS-L). The TCIS-H group was significantly associated with a longer PFS (p < 0.001). Furthermore, the ICIS-H group was additionally associated with a longer PFS (p < 0.001) and overall survival (OS; p = 0.001), at significant levels. In the multivariate analysis, both TCIS-H and ICIS-H groups were identified as independent predictors of favorable PFS (p = 0.012 and p = 0.001, respectively). ICIS-H was also shown to be an independent predictor of favorable OS (p = 0.003). The analysis of the mRNA expression data from TCGA also validated our findings regarding TNBC.</p><p><strong>Conclusion: </strong>Our novel TCIS and ICIS exhibited a significant prognostic value in TNBC. Additional research would be needed to strengthen our findings and identify the most efficient prognostic and predictive biomarkers for TNBC patients.</p>","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"25 1","pages":"134"},"PeriodicalIF":7.4,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71478217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer","authors":"L. Ratz, C. Brambillasca, L. Bartke, Maxim A Huetzen, J. Goergens, Orsolya Leidecker, R. Jachimowicz, M. van de Ven, N. Proost, Bjørn Siteur, Renske de Korte-Grimmerink, P. Bouwman, Emilia M. Pulver, Roebi de Bruijn, J. Isensee, T. Hucho, Gaurav Pandey, M. van Lohuizen, P. Mallmann, H. Reinhardt, J. Jonkers, J. Puppe","doi":"10.1186/s13058-022-01534-y","DOIUrl":"https://doi.org/10.1186/s13058-022-01534-y","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65772688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multiple roles for Bcl-3 in mammary gland branching, stromal collagen invasion, involution and tumor pathology","authors":"D. Carr, A. Zein, J. Coulombe, Tianqi Jiang, M. A. Cabrita, Gwendoline C. D. Ward, Manijeh Daneshmand, A. Sau, M. Pratt","doi":"10.1186/s13058-022-01536-w","DOIUrl":"https://doi.org/10.1186/s13058-022-01536-w","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2022-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65772694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inducible localized delivery of an anti-PD-1 scFv enhances anti-tumor activity of ROR1 CAR-T cells in TNBC","authors":"M. Harrasser, S. Gohil, H. Lau, M. della Peruta, Vincent Muczynski, Dominic Patel, Elena Miranda, Kristiana Grigoriadis, A. Grigoriadis, D. Granger, R. Evans, A. Nathwani","doi":"10.1186/s13058-022-01531-1","DOIUrl":"https://doi.org/10.1186/s13058-022-01531-1","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65772640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia-regulated carbonic anhydrase IX (CAIX) protein is an independent prognostic indicator in triple negative breast cancer","authors":"Chong Hui Clara Ong, Dong Yeul Lee, Bernett Lee, Huihua Li, J. Lim, Johnathan Xiande Lim, J. Yeong, H. Lau, A. Thike, P. Tan, J. Iqbal","doi":"10.1186/s13058-022-01532-0","DOIUrl":"https://doi.org/10.1186/s13058-022-01532-0","url":null,"abstract":"","PeriodicalId":9222,"journal":{"name":"Breast Cancer Research","volume":"24 1","pages":""},"PeriodicalIF":7.4,"publicationDate":"2022-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"65772647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}