Breast Cancer : Targets and Therapy最新文献

{"title":"A Review on the Management of Peripheral Neuropathic Pain Following Breast Cancer.","authors":"Francisco Avila,&nbsp;Ricardo Torres-Guzman,&nbsp;Karla Maita,&nbsp;John P Garcia,&nbsp;Gioacchino D De Sario,&nbsp;Sahar Borna,&nbsp;Olivia A Ho,&nbsp;Antonio J Forte","doi":"10.2147/BCTT.S386803","DOIUrl":"https://doi.org/10.2147/BCTT.S386803","url":null,"abstract":"<p><p>Postmastectomy pain syndrome (PMPS) is a common and debilitating form of postsurgical pain with neuropathic characteristics, presenting as burning, stabbing, or pulling sensations after mastectomy, lumpectomy, or other breast procedures. With a prevalence of 31%, the risk factors for PMPS include younger age, psychosocial factors, radiotherapy, axillary lymph node dissection, and a history of chronic pain. This review evaluates the pharmacological and surgical options for managing PMPS. Pharmacological treatment options include antidepressants, gabapentinoids, levetiracetam, capsaicin, and topical lidocaine. Procedural and surgical options include fat grafting, nerve blocks, radiofrequency ablation, peripheral nerve surgery, serratus plane block, and botulinum toxin injections. Despite the variety of therapeutic options available for patients, further randomized trials are required to conclude whether these treatments reduce the intensity of neuropathic pain in patients with PMPS. In particular, comparative studies and the inclusion of patients across a range of pain intensities will be essential to developing a treatment algorithm for PMPS. In conclusion, current management for these patients should be tailored to their individual requirements.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"761-772"},"PeriodicalIF":2.6,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71477872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Traditional Chinese Medicine for Breast Cancer: A Review.","authors":"Rui-Qi Feng,&nbsp;De-Hui Li,&nbsp;Xu-Kuo Liu,&nbsp;Xiao-Hui Zhao,&nbsp;Qian-Er Wen,&nbsp;Ying Yang","doi":"10.2147/BCTT.S429530","DOIUrl":"https://doi.org/10.2147/BCTT.S429530","url":null,"abstract":"<p><p>A total of 18% of global breast cancer (BC) deaths are attributed to BC in China, making it one of the five most common cancers there. There has been a steady rise in BC morbidity and mortality in women in the last few years and it is now a leading cancer among Chinese women. Conventional treatments for BC are currently effective but have several limitations and disadvantages, and Traditional Chinese medicine (TCM) plays a vital role in the overall process of cancer prevention and therapy. It is known that TCM can treat a variety of conditions at a variety of sites and targets. In recent years, increasingly, research has been conducted on TCM's ability to treat BC. TCM has shown positive results in the treatment of breast cancer and the adverse effects of radiotherapy and chemotherapy. This review describes the progress of clinical observation and mechanism research of TCM in the treatment of breast cancer in recent years. It provides some ideas and theoretical basis for the treatment of BC with TCM.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"747-759"},"PeriodicalIF":2.6,"publicationDate":"2023-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10617532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71420631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PDL1-Based Nomogram May Be of Potential Clinical Utility for Predicting Survival Outcome in Stage III Breast Cancer.","authors":"Xi Zhang,&nbsp;Ruzhe Li,&nbsp;Guonian Wang","doi":"10.2147/BCTT.S435980","DOIUrl":"10.2147/BCTT.S435980","url":null,"abstract":"<p><strong>Purpose: </strong>Programmed cell death ligand 1 (PDL1) has the predictive and prognostic value in a great deal of cancers. This study aims to explore the expression of PDL1 in stage III breast cancer (BC) and its correlation with clinical outcome.</p><p><strong>Methods: </strong>The protein expression of PDL1 in tumor tissues was determined by immunohistochemistry (IHC). The correlations between PDL1 and clinicopathological variables were performed by <i>χ²</i>-tests or Fisher's exact tests. The Cox proportional hazards model was used for univariate and multivariate analysis of the potential prognostic factors. Survival curves were estimated based on Kaplan-Meier analyses, and Log Rank test was used to contrast factors influencing the survival outcome.</p><p><strong>Results: </strong>On the basis of the semiquantitative scoring method for PDL1 expression, the patients were divided into low PDL1 expression group (109 cases) and high PDL1 expression group (107 cases). PDL1 expression was correlated with positive lymph nodes, positive axillary lymph nodes, postoperative radiotherapy, and CK5/6 expression (P < 0.05). The PDL1 expression in tumor tissues was discovered to be a potential prognostic risk factor with the disease-free survival (DFS) and overall survival (OS) for stage III BC. Moreover, patients with high PDL1 expression showed longer lifetime (DFS and OS) compared to those with low PDL1 expression in total patient population (P < 0.05). Moreover, the nomogram showed that the prediction line is in good agreement with the reference line for postoperative 1-, 3-, and 5-year lifetime. The DCA curve showed that the 3- and 5-year lifetime by nomogram had so much better divination of the clinical application than only by PDL1.</p><p><strong>Conclusion: </strong>PDL1 is a latent prognostic factor in stage III BC and is closely related to some clinicopathological features. PDL1 expression in tumor tissues is significantly associated with better lifetime rate in stage III BC.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"731-746"},"PeriodicalIF":2.6,"publicationDate":"2023-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10613449/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71410517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Cancer: An Overview of Current Therapeutic Strategies, Challenge, and Perspectives.","authors":"Jun Wang,&nbsp;San-Gang Wu","doi":"10.2147/BCTT.S432526","DOIUrl":"10.2147/BCTT.S432526","url":null,"abstract":"<p><p>Breast cancer is the most commonly diagnosed cancer and the leading cause of death among female patients, which seriously threatens the health of women in the whole world. The treatments of breast cancer require the cooperation of a multidisciplinary setting and taking tumor load and molecular makers into account. For early breast cancer, breast-conserving surgery with radiotherapy or mastectomy alone remains the standard management, and the administration of adjuvant systemic therapy is decided by the status of lymph nodes, hormone receptors, and human epidermal growth factor receptor-2. For metastatic breast cancer, the goal of treatments is to prolong survival and maintain quality of life. This review will present the current advances and controversies of surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, gene therapy, and other innovative treatment strategies in early-stage and metastatic breast cancer.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"15 ","pages":"721-730"},"PeriodicalIF":2.6,"publicationDate":"2023-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/86/d4/bctt-15-721.PMC10596062.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50160659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Characteristics and Survival Outcomes of Patients with De Novo Metastatic Breast Cancer.","authors":"Hanan Almasri,&nbsp;Ayah Erjan,&nbsp;Hebah Abudawaba,&nbsp;Khaled Ashouri,&nbsp;Sara Mheid,&nbsp;Anoud Alnsour,&nbsp;Hikmat Abdel-Razeq","doi":"10.2147/BCTT.S383874","DOIUrl":"https://doi.org/10.2147/BCTT.S383874","url":null,"abstract":"<p><strong>Purpose: </strong>Though less than 5% of patients with breast cancer present with De Novo Metastasis (dnMBC) in Western societies, this percentage may reach 30% in developing countries. In this study, we present survival outcomes of patients diagnosed with dnMBC treated at a tertiary center in a developing country.</p><p><strong>Patients and methods: </strong>Using hospital-based database, consecutive patients with dnMBC diagnosed between 2013 and 2017 were identified. Demographic data, tumor characteristics, types of treatment, and survival data were retrospectively collected.</p><p><strong>Results: </strong>A total of 435 patients were included; median age (range) at time of diagnosis was 51 (24-85) years. Most of the tumors expressed hormone receptors (81% Estrogen Receptor positive, 77% Progesterone Receptor positive). Human epidermal growth factor receptor-2 (HER2) overexpression was reported in 134 (30.9%) patients, while only 24 (5.5%) had Triple Negative (TN) disease. Bone, lung and liver were the most common sites of metastasis involved in 70.6%, 36.1%, and 32.0%, respectively. The median Overall Survival (OS) for all patients was 38 months, and 5-year OS was 32.6%. On univariate analysis, high tumor grade, advanced T-stage, TN-disease and metastasis to multiple sites, but not HER2 status, were associated with poor OS. On multivariate analysis, high tumor grade (Hazard Ratio =1.6, p=0.002), advanced T-stage (Hazard Ratio=1.6, p=0.003), and triple negative status (Hazard Ratio= 2.1, p=0.008) predicted poor OS.</p><p><strong>Conclusion: </strong>The overall survival of patients with dnMBC remains poor. Better understanding of the disease behavior and factors affecting survival is required for optimal utilization of available regimens and new drugs to hopefully improve patients' outcomes.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":" ","pages":"363-373"},"PeriodicalIF":2.6,"publicationDate":"2022-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/89/5d/bctt-14-363.PMC9628702.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40685209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Involvement of Insulin-Like Growth Factor 2 Messenger Ribonucleic Acid-Binding Protein 2 in the Regulation of the Expression of Breast Cancer-Related Genes.","authors":"Chao Gao,&nbsp;Li Li,&nbsp;Xixin Jin,&nbsp;Xinyu Song,&nbsp;Huiling Li,&nbsp;Xiaoli Xu,&nbsp;Chao Dong,&nbsp;Binlin Ma","doi":"10.2147/BCTT.S382566","DOIUrl":"https://doi.org/10.2147/BCTT.S382566","url":null,"abstract":"<p><strong>Aim: </strong>This study investigated the role and mechanism of insulin-like growth factor 2-IGF2BP2 in breast cancer.</p><p><strong>Methods: </strong>IGF2BP2 is overexpressed in MDA-MB-231 human breast cancer cells. Thus, RNA sequencing was used to analyze the differentially expressed genes, Cell Counting Kit-8 was used to detect cell proliferation, and a Transwell assay was used to assess cell invasion. Following on from the RNA sequencing results, Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2), chemokine C-C motif ligand 20 (CCL20), chemokine C-C motif ligand 5 (CCL5), and chemokine C-X-C motif ligand 10 (CXCL10) regulated by IGF2BP2 were subjected to real-time reverse transcriptase-polymerase chain reaction verification.</p><p><strong>Results: </strong>After IGF2BP2 overexpression, 67 genes were up-regulated, and 87 genes were down-regulated. The gene with the most significant up-regulation was homeobox protein 1 (PROX1), and the gene with the most significant down-regulation was Acidic β-crystallin 4 (CRYBA4). The most enriched gene ontology (GO) terms of up-regulated differentially expressed genes are protein binding and cell membrane and of down-regulated differentially expressed genes they are ion binding, cytoplasm, and response to virus. Kyoto Encyclopedia of Genes and Genomes analysis showed that the up-regulated differential genes were mainly enriched in protein processing, the endoplasmic reticulum, and the regulation of actin cytoskeleton, while down-regulated differential genes were mainly enriched in rheumatoid arthritis, chemokine signaling pathways, toll-like receptor signaling pathways, tumor necrosis factor signaling pathways, cytokine-cytokine receptor interaction, and Notch signaling pathways. IGF2BP2 overexpression significantly promoted the proliferation and invasion of breast cancer cells (<i>P</i> < 0.01). Compared with the control group, the IGF2BP2 overexpression group had significantly increased expressions of IFIT2, CCL20, and CXCL10 (<i>P</i> < 0.05).</p><p><strong>Conclusion: </strong>IGF2BP2 may promote the invasion and proliferation of human breast cancer cells by up-regulating breast cancer-related genes, such as IFIT2, CCL20, and CXCL10.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":" ","pages":"311-322"},"PeriodicalIF":2.6,"publicationDate":"2022-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/48/a0/bctt-14-311.PMC9553167.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33509133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Notch Signaling Pathway Contributes to Angiogenesis and Tumor Immunity in Breast Cancer.","authors":"Nina Jiang,&nbsp;Ye Hu,&nbsp;Meiling Wang,&nbsp;Zuowei Zhao,&nbsp;Man Li","doi":"10.2147/BCTT.S376873","DOIUrl":"https://doi.org/10.2147/BCTT.S376873","url":null,"abstract":"<p><p>Breast cancer in women is the first leading tumor in terms of incidence worldwide. Some subtypes of BC lack distinct molecular targets and exhibit therapeutic resistance; these patients have a poor prognosis. Thus, the search for new molecular targets is an ongoing challenge for BC therapy. The Notch signaling pathway is found in both vertebrates and invertebrates, and it is a highly conserved in the evolution of the species, controlling cellular fates such as death, proliferation, and differentiation. Numerous studies have shown that improper activation of Notch signaling may lead to excessive cell proliferation and cancer, with tumor-promoting and tumor-suppressive effects in various carcinomas. Thus, inhibitors of Notch signaling are actively being investigated for the treatment of various tumors. The role of Notch signaling in BC has been widely studied in recent years. There is a growing body of evidence suggesting that Notch signaling has a pro-oncogenic role in BC, and the tumor-promoting effect is largely a result of the diverse nature of tumor immunity. Immunological abnormality is also a factor involved in the pathogenesis of BC, suggesting that Notch signaling could be a target for BC immunotherapies. Furthermore, angiogenesis is essential for BC growth and metastasis, and the Notch signaling pathway has been implicated in angiogenesis, so studying the role of Notch signaling in BC angiogenesis will provide new prospects for the treatment of BC. We summarize the potential roles of the current Notch signaling pathway and its inhibitors in BC angiogenesis and the immune response in this review and describe the pharmacological targets of Notch signaling in BC, which may serve as a theoretical foundation for future research into exploring this pathway for novel BC therapies.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":" ","pages":"291-309"},"PeriodicalIF":2.6,"publicationDate":"2022-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a7/96/bctt-14-291.PMC9526507.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33487548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Routine Intraoperative Frozen Section Analysis of Sentinel Lymph Nodes Necessary in Every Early-Stage Breast Cancer?","authors":"Bhoowit Lerttiendamrong,&nbsp;Nattanan Treeratanapun,&nbsp;Voranaddha Vacharathit,&nbsp;Kasaya Tantiphlachiva,&nbsp;Phuphat Vongwattanakit,&nbsp;Sopark Manasnayakorn,&nbsp;Mawin Vongsaisuwon","doi":"10.2147/BCTT.S380579","DOIUrl":"https://doi.org/10.2147/BCTT.S380579","url":null,"abstract":"<p><strong>Purpose: </strong>Clinical application of the ACOSOG Z0011 trial results allows clinically node-negative breast cancer patients who meet criteria to avoid axillary dissection even when 1-2 sentinel lymph nodes (SLNs) are positive for metastatic disease. Intraoperative frozen section (iFS) analyses of SLNs were thought to reduce re-operation rates despite variable reported sensitivity and possibility of a false negative result. This study evaluated the rate of re-operations prevented by SLN iFS in a tertiary care hospital in Bangkok, Thailand, over a 6-year time-frame.</p><p><strong>Patients and methods: </strong>From April 2016 to April 2022, 1284 sentinel lymph node biopsy (SLNB) procedures were performed. Of these, 214 cases were breast-conserving surgery in accordance with the ACOSOG criteria with concomitant usage of iFS. Clinicopathological features of these cases were collected and analyzed. Re-operation rates prevented by the additional intervention were reported.</p><p><strong>Results: </strong>Only five additional operations were prevented with the usage of 214 iFS. The discordance rate between frozen and permanent sections in terms of presence of metastatic disease and number of total lymph nodes was around 15%. Tumor staging, node staging, Nottingham histologic grading and lymphovascular invasion are significant predictors of SLN metastasis.</p><p><strong>Conclusion: </strong>iFS results in a very low prevention rate for follow-up ALND in patients with preoperative clinically negative axillary nodes and is associated with a non-negligible discordance rate with permanent sections. Our study suggests iFS may be avoided in most cases of early-stage clinically and radiographically node-negative breast cancer patients. Doing so may reduce surgical costs and total operative time without a significant impact on the overall quality of treatment and standard of care.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":" ","pages":"281-290"},"PeriodicalIF":2.6,"publicationDate":"2022-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/9e/d4/bctt-14-281.PMC9507279.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33485158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Breast Cancer Subtypes and Prognosis: Answers to Subgroup Classification Questions, Identifying the Worst Subgroup in Our Single-Center Series.","authors":"Rusen Cosar,&nbsp;Necdet Sut,&nbsp;Alaattin Ozen,&nbsp;Ebru Tastekin,&nbsp;Sernaz Topaloglu,&nbsp;Irfan Cicin,&nbsp;Dilek Nurlu,&nbsp;Talar Ozler,&nbsp;Seda Demir,&nbsp;Gokay Yıldız,&nbsp;Eylül Şenödeyici,&nbsp;Mustafa Cem Uzal","doi":"10.2147/BCTT.S380754","DOIUrl":"https://doi.org/10.2147/BCTT.S380754","url":null,"abstract":"<p><strong>Purpose: </strong>Many studies report the triple negative breast cancer (TNBC) as the worst subgroup, as such patients do not benefit from anti-hormonal therapy and human epidermal growth factor receptor 2 (HER2) antagonists. While HER2 overexpression was a poor prognostic factor in breast cancer before trastuzumab (Herceptin) was available, TNBC is often reported as the worst BC subgroup since targeted therapy is currently not possible. Since the patience-specific experiences and the current literature did not always align, we aimed to determine the BC subgroup with the shortest survival in our center.</p><p><strong>Methods: </strong>The records of patients with BC who were admitted to Trakya University Faculty of Medicine Department of Medical and Radiation Oncology between July 1999 and December 2019 were reviewed. Patients were divided into four main groups (Luminal A, Luminal B, TNBC, and HER2-enriched) according to the St Gallen International Consensus Panel and four subgroups in accordance with estrogen receptor, progestin receptor and HER2 positivity. Patient characteristics, treatment characteristics and clinical outcomes of the four main subgroups were evaluated. Survival curves were generated using the Kaplan-Meier method, and the significance of survival differences among the selected variables was compared by using the Log rank test. Factors affecting disease-free survival (DFS) and overall survival (OS) were analyzed by Cox regression analysis.</p><p><strong>Results: </strong>Statistical analysis was performed on 2017 patients, after excluding patients with phyllodes tumor, carcinoma-in-situ and missing information from a total of 2474 patients with BC. There were 952 (47.1%) patients in the Luminal A group, 236 (34.1%) in the Luminal B group, 236 (11.7%) in the TNBC group and 142 (7.1%) patients in the HER2 enriched group. HER2-enriched patients had the shortest survival (p < 0.001), with 113.70 ± 7.17 months of DFS and 125.45 ± 3.03 months of OS. For patients who received Herceptin, DFS was 101.50 ± 6.4 months and OS was 118.14 ± 6.16. Patients who did not receive Herceptin had 92.79 ± 18 months of DFS and 94.44 ± 15.23 months of OS.</p><p><strong>Conclusion: </strong>The HER2-enriched subgroup had the worst prognosis despite receiving targeted therapy. While the duration of DFS and OS had no significant difference between TNBC and Luminal A-B subgroups, HER2 enriched subgroup had significantly shorter survival when compared to any other subgroup. HER2-enriched subgroup had a 10-fold greater risk of death compared to the Luminal A subgroup.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":" ","pages":"259-280"},"PeriodicalIF":2.6,"publicationDate":"2022-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/25/bctt-14-259.PMC9467695.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40355956","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-623 Targets Metalloproteinase-1 and Attenuates Extravasation of Brain Metastatic Triple-Negative Breast Cancer Cells.","authors":"Dua Hammash,&nbsp;Mona Mahfood,&nbsp;Ghalia Khoder,&nbsp;Munazza Ahmed,&nbsp;Abdelaziz Tlili,&nbsp;Rifat Hamoudi,&nbsp;Rania Harati","doi":"10.2147/BCTT.S372083","DOIUrl":"https://doi.org/10.2147/BCTT.S372083","url":null,"abstract":"<p><strong>Background: </strong>Most breast cancer-related deaths result from metastasis. Understanding the molecular basis of metastasis is needed for the development of effective targeted and preventive strategies. Matrix metalloproteinase-1 (MMP1) plays an important role in brain metastasis (BM) of triple-negative breast cancer (TNBC) by promoting extravasation of cancer cells across the brain endothelium (BE). MMP1 expression is controlled by endogenous microRNAs. Preliminary bioinformatics analysis has revealed that miR-623, known to target the 3'UTR of MMP1, is significantly downregulated in brain metastatic tumors compared to primary BC tumors. However, the involvement of miR-623 in MMP1 upregulation in breast cancer brain metastatic cells (BCBMC) remains unexplored. Here, we investigated the role of miR-623 in MMP1 regulation and its impact on the extravasation of TNBC cells through the BE in vitro.</p><p><strong>Materials and methods: </strong>A loss-and-gain of function method was employed to address the effect of miR-623 modulation on MMP1 expression. MMP1 regulation by miR-623 was investigated by real-time PCR, western blot, luciferase and transwell migration assays using an in vitro human BE model.</p><p><strong>Results: </strong>Our results confirmed that brain metastatic TNBC cells express lower levels of miR-623 compared with cells having low propensity to spread toward the brain. miR-623 binds to the 3'-untranslated region of MMP1 transcript and downregulates its expression. Restoring miR-623 expression significantly decreased MMP1 expression, preserved the endothelial barrier integrity, and attenuated transmigration of BCBMC through the BE.</p><p><strong>Conclusion: </strong>Our study elucidates, for the first time, the crucial role of miR-623 as MMP1 direct regulator in BCBMC and sheds light on miR-623 as a novel therapeutic target that can be exploited to predict and prevent brain metastasis in TNBC. Importantly, the presents study helps in unraveling a brain metastasis-specific microRNA signature in TNBC that can be used as a guide to personalized metastasis prediction and preventive approach with better therapeutic outcome.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":" ","pages":"187-198"},"PeriodicalIF":2.6,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/4a/b4/bctt-14-187.PMC9354772.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40593095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}