Breast Cancer Research最新文献

英文中文

Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA 治疗蛋白PAK通过降解SREBP-1 mRNA抑制三阴性乳腺癌的进展

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2023-12-11 DOI: 10.1186/s13058-023-01749-7

Pan Hu, Peiyi Zhou, Tieyun Sun, Dingkang Liu, Jun Yin, Lubin Liu

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.

三阴性乳腺癌（TNBC）是最具挑战性的乳腺癌亚型。研究表明，脂质合成途径的上调与 TNBC 的发生和发展有关。靶向脂质合成途径可能是治疗 TNBC 的一种有前景的策略。我们之前的研究开发了一种具有被动靶向性并能抑制肿瘤增殖的治疗性蛋白 PAK。在本研究中，我们进一步证实了PAK对TNBC的疗效。转录组测序分析显示，PAK介导了参与脂肪酸合成的基因下调，包括SREBP-1、FASN和SCD1等关键基因。RNA 免疫沉淀实验表明，PAK 与 SREBP-1 mRNA 有显著的结合亲和力，促进了其降解过程。在体外和体内模型中，PAK都通过下调脂质合成途径阻碍了TNBC的进展。总之，本研究强调了PAK通过与SREBP-1 mRNA结合并降解SREBP-1 mRNA来抑制TNBC的进展，揭示了一种在TNBC干预中调节脂质合成的新策略及其治疗意义。

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引用次数: 0

Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study 蚊虫控制暴露与乳腺癌风险：对加纳乳房健康研究中的 1071 例病例和 2096 例对照的分析

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2023-12-11 DOI: 10.1186/s13058-023-01737-x

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

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.

有关杀虫剂暴露和乳腺癌风险的流行病学数据尚无定论，且大多来自高收入国家。利用加纳乳房健康研究（Ghana Breast Health Study）在 2013 年至 2015 年期间收集的 1071 例经病理证实的侵袭性乳腺癌病例和 2096 例对照者的数据，我们调查了蚊虫控制产品与减少疟疾等蚊媒疾病传播的关系。这些防蚊产品包括驱虫蚊帐、蚊香、室内驱蚊喷雾剂和个人防蚊护肤霜。我们使用多变量和多项式逻辑回归模型来估计乳腺癌风险的几率比（ORadj）和 95% 的置信区间（CI），并对潜在的混杂因素和已知的风险因素进行了调整。在对照组中，报告使用的灭蚊产品是蚊香（65%），其次是驱虫蚊帐（56%）、驱蚊室内喷雾剂（53%）和驱蚊护肤霜（15%）。与未接触过灭蚊产品的参照组相比，乳腺癌风险与蚊香之间没有显著关联。据报告，乳腺癌风险与使用驱虫蚊帐之间存在关联；但是，这种关联很弱，在统计学上并不显著。与不使用任何灭蚊产品的妇女相比，报告使用驱蚊喷雾的参与者患乳腺癌的风险更高，即使在对所有其他灭蚊产品进行调整后也是如此（OR = 1.42，95% CI=1.15-1.75）。我们检测驱蚊护肤霜相关性的能力有限。尽管只有少数参与者表示每周/每天或 0.25 次使用驱蚊室内喷雾。）在确定驱蚊护肤霜是否存在关联时，我们的分析是有限的；因此，我们无法得出结论。我们发现与广泛使用的蚊香和驱虫蚊帐有关的风险证据有限，鉴于它们对预防疟疾的重要性，这一点令人欣慰。我们关于特定乳腺癌风险关联的研究结果，特别是驱蚊喷雾剂之间的关联，还需要进一步研究。

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引用次数: 0

Molecular subtypes of breast cancer predicting clinical benefits of radiotherapy after breast-conserving surgery: a propensity-score-matched cohort study 预测保乳手术后放疗临床疗效的乳腺癌分子亚型：倾向分数匹配队列研究

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2023-12-08 DOI: 10.1186/s13058-023-01747-9

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

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.

根据癌细胞的分子表达，乳腺癌分子亚型已被用于对患者进行分类，以预测临床结果和预后。然而，关于分子亚型对保乳手术（BCS）后放疗（RT）疗效的影响还需要进一步的证据，尤其是在基于人群的背景下。因此，本研究采用倾向分数匹配队列设计，研究分子亚型对保乳术后放疗患者预后分层的潜在作用，并确定可能出现的特定临床益处。从2006年到2019年，本研究纳入了59502名接受BCS治疗的乳腺癌患者，这些患者来自台湾国民健康保险研究数据库。研究采用倾向评分法来匹配每种乳腺癌亚型（即管腔A型、管腔B型/HER2阴性、管腔B型/HER2阳性、基底样和HER2富集型）中接受和未接受RT治疗的患者之间的混杂变量。我们从局部复发（LR）、区域复发（RR）、远处转移（DM）、无病生存期（DFS）和总生存期（OS）等方面对几种临床结果进行了评估。在BCS RT后，管腔A和管腔B/HER2阳性乳腺癌患者的LR有所下降（调整后危险比[aHR] = 0.18，p < 0.0001；和0.24，p = 0.0049）。此外，在管腔A型（aHR = 0.15，p = 0.0004；0.29，p < 0.0001）、管腔B型/HER2阴性（aHR = 0.06，p = 0.0093；0.46，p = 0.028）和管腔B型/HER2阳性（aHR = 0.14，p = 0.01；0.38，p < 0.0001）乳腺癌患者中观察到RR降低和DFS改善。值得注意的是，管腔A型（aHR = 0.62，p = 0.002）、管腔B型/HER2阴性（aHR = 0.30，p < 0.0001）、基底样（aHR = 0.40，p < 0.0001）和HER2富集（aHR = 0.50，p = 0.03）患者的OS获益，但管腔B型/HER2阳性患者的OS获益则不明显。值得注意的是，在考虑DM时，接受RT治疗的管腔A型患者的DM累积发生率低于未接受RT治疗的患者（p = 0.02）。对于接受 BCS 的管腔 A 型乳腺癌患者，RT 可以降低肿瘤转移的可能性。RT 后，肿瘤的激素受体状态可预测肿瘤在 LR、RR 和 DFS 方面的控制情况。此外，管腔型乳腺癌患者的 HER2 状态可能是预测乳腺癌术后 RT OS 的额外指标。然而，这些发现还需要进一步的前瞻性研究来验证。

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引用次数: 0

Alterations to DNA methylation patterns induced by chemotherapy treatment are associated with negative impacts on the olfactory pathway. 化疗引起的DNA甲基化模式的改变与嗅觉通路的负面影响有关。

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2023-11-06 DOI: 10.1186/s13058-023-01730-4

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

Background: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients.

Methods: 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).

Results: 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).

Conclusion: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.

背景：暴露于细胞毒性化疗可能改变癌症患者的DNA甲基化（DNAm）。方法：采用Illumina MethylationEPIC阵列，对125例癌症患者化疗前后进行DNA分析。使用经单核细胞比例调整的线性回归模型评估588798个CpG个体（包括41207个启动子区）的DNAm变化。进行基因集富集分析（GSEA）以确定与化疗相关的关键基因本体论（GO）生物学过程或京都基因和基因组百科全书（KEGG）途径。结果在接受治疗的癌症患者的单独队列中得到验证（n = 1273）和未处理（n = 872）通过化疗（1808份血液，337份唾液）。结果：在配对样本和单时间点分析中，经过多次测试校正，共有141个差异甲基化CpG和11个启动子与化疗显著相关。启动子区的GSEA（通过测试统计进行预排序）确定了六个被抑制的生物过程（p 成对样本 = 1.72e-9，p单个时间点血液 = 2.03e-15和单个时间点唾液 = 7.52e-56）。结论：印迹基因在生物学过程和途径中的富集表明了化疗可能影响嗅觉的生物学机制。

{"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":"Background: Exposure to cytotoxic chemotherapy treatment may alter DNA methylation (DNAm) in breast cancer patients.Methods: 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).Results: 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 (ppaired-samples = 1.72e-9, psingle-timepoint-blood = 2.03e-15 and psingle-timepoint-saliva = 7.52e-56).Conclusion: The enrichment of imprinted genes within biological processes and pathways suggests a biological mechanism by which chemotherapy could affect the perception of smell.","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}

引用次数: 0

Exploring the interface zone in breast cancer: implications for surgical strategies and beyond. 探索乳腺癌症的交界区：对外科手术策略的影响及展望。

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2023-11-03 DOI: 10.1186/s13058-023-01734-0

Kefah Mokbel, Munaser Alamoodi

引用次数: 0

The prognostic value of a combined immune score in tumor and immune cells assessed by immunohistochemistry in triple-negative breast cancer. 免疫组化评估肿瘤和免疫细胞联合免疫评分对癌症三阴性乳腺癌的预后价值。

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2023-11-03 DOI: 10.1186/s13058-023-01710-8

Ji Eun Choi, Jae Seok Lee, Min-Sun Jin, Ilias P Nikas, Kwangsoo Kim, Sunah Yang, Soo Young Park, Jiwon Koh, Sohyeon Yang, Seock-Ah Im, Han Suk Ryu

Background: This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC).

Methods: 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.

Results: 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.

Conclusion: 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.

背景：本研究旨在建立一种新的基于联合免疫评分（CIS）的癌症三阴性预后评估模型，随后与选定的临床病理参数和生存率相关。从癌症基因组图谱（TCGA）检索的数据被进一步检查以验证我们的发现。结果：除PD-1在TC中不表达外，所有免疫标志物均在TC和IC中表达。在IC中，除了PD-L1和OX40之间，以及TIM3和OX4之间，所有免疫标志物的表达彼此呈正相关。在ICs中，PD-1、PD-L1和OX40L阳性表达与较长的无进展生存期相关（PFS；p = 0.040，p = 0.020和p = 0.020）。在TC中，OX40阳性表达与较短的PFS相关（p = 0.025）。随后，根据TCs（TCIS-H或TCIS-L）和ICs（ICIS-H或ICIS-L）中选择的生物标志物的表达水平，将TNBC患者分为高和低联合免疫评分组（CIS-H和CIS-L）。TCIS-H组与较长的PFS显著相关（p 结论：我们的新TCIS和ICIS在TNBC中显示出显著的预后价值。需要更多的研究来加强我们的发现，并确定TNBC患者最有效的预后和预测生物标志物。

{"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, Jae Seok Lee, Min-Sun Jin, Ilias P Nikas, Kwangsoo Kim, Sunah Yang, Soo Young Park, Jiwon Koh, Sohyeon Yang, Seock-Ah Im, Han Suk Ryu","doi":"10.1186/s13058-023-01710-8","DOIUrl":"https://doi.org/10.1186/s13058-023-01710-8","url":null,"abstract":"Background: This study aimed to develop a novel combined immune score (CIS)-based model assessing prognosis in triple-negative breast cancer (TNBC).Methods: 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.Results: 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.Conclusion: 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.","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}

引用次数: 0

Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer 联合抑制EZH2和ATM在brca1缺陷乳腺癌中是合成致死性的

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2022-06-17 DOI: 10.1186/s13058-022-01534-y

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

引用次数: 2

Multiple roles for Bcl-3 in mammary gland branching, stromal collagen invasion, involution and tumor pathology Bcl-3在乳腺分支、间质胶原浸润、内陷和肿瘤病理中的多重作用

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2022-06-09 DOI: 10.1186/s13058-022-01536-w

D. Carr, A. Zein, J. Coulombe, Tianqi Jiang, M. A. Cabrita, Gwendoline C. D. Ward, Manijeh Daneshmand, A. Sau, M. Pratt

引用次数: 1

Inducible localized delivery of an anti-PD-1 scFv enhances anti-tumor activity of ROR1 CAR-T cells in TNBC 诱导局部递送抗pd -1 scFv增强TNBC中ROR1 CAR-T细胞的抗肿瘤活性

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2022-06-03 DOI: 10.1186/s13058-022-01531-1

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

引用次数: 8

Hypoxia-regulated carbonic anhydrase IX (CAIX) protein is an independent prognostic indicator in triple negative breast cancer 低氧调节碳酸酐酶IX (CAIX)蛋白是三阴性乳腺癌的独立预后指标

IF 7.4 1区医学 Q1 ONCOLOGY

Breast Cancer Research

Pub Date : 2022-06-03 DOI: 10.1186/s13058-022-01532-0

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

引用次数: 16

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