Breast Cancer : Targets and Therapy最新文献

{"title":"Targeting erbB Pathways in Breast Cancer: Dual Kinase Inhibition for Brain Metastasis and Prevention of p185HER2/Neu Tumor Development.","authors":"Peeyush N Goel, Makoto Katsumata, Wei Qian, Sunil Mathur, Mei Q Ji, Arabinda Samanta, Payal Grover, George Sgouros, Jenny C Chang, Mark I Greene","doi":"10.2147/BCTT.S490904","DOIUrl":"10.2147/BCTT.S490904","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer predominantly affects women and poses challenges in the treatment of both local and advanced diseases. In a previous study, we reported the effectiveness of ER121, a structurally resolved small compound specifically designed to target human cancers expressing or overexpressing mutant EGFR and HER2.</p><p><strong>Purpose: </strong>The objective of this study is to assess the efficacy and toxicity of ER121 in metastatic and triple negative breast cancer (TNBC, HER2+) cells and tumor models. The Herceptin-resistant breast cancer cell line JIMT-1 was used in an in vivo tumor model, and MMTV-erbB2 (Fo5) transgenic mice models were used to evaluate the efficacy and safety of ER121 as neoadjuvant.</p><p><strong>Methods: </strong>ER121 treatment focusing on experimental brain metastasis in TNBC, HER2+ model, was quantified by total flux employing the In Vivo Imaging System (IVIS). We also compared the brain tissue from the treated and the controls groups. Additionally, ER121 was evaluated in JIMT-1, a Herceptin-resistant breast cancer cell line, both in vitro and in vivo tumor model. We also administered ER121 orally in neoadjuvant model with the MMTV-erbB2 (Fo5) transgenic mice, the survival rates were compared with the control group. Tumor-free survival of multiple treated groups were analyzed by Kaplan-Meier analysis employing the log-rank test with the Bonferroni correction using R Statistical Software.</p><p><strong>Results: </strong>In this study, we present findings indicating that ER121 treatment significantly attenuated breast tumor growth using a TNBC, HER2+ model, focusing on experimental brain metastasis, as quantified by total flux employing IVIS. These observations were further corroborated by analysis of brain tissue from the treatment group compared to controls. Data is presented as Mean ± S.D. statistical significance was calculated using Student <i>t</i> test (*<i>p</i> < 0.05). Additionally, ER121 significantly inhibited JIMT-1, a Herceptin-resistant breast cancer cell line was used in vivo xenograft model. Additionally, we used a neoadjuvant model with the MMTV-erbB2 (Fo5) transgenics and the tumor-free survival rates exhibited a remarkable difference between the control and treated groups when ER121 was administered orally. We found statistically significant p values of 0.048 employing log-rank test with Bonferroni Correction for comparing ER121 high, ER121 Low, Herceptin and PBS groups. All analyses were performed using R Statistical Software.</p><p><strong>Conclusion: </strong>ER121 is a non-toxic small-molecule erbB kinase inhibitor and holds promise as an oral and systemic therapeutic agent for treating progressive erbB-driven tumors in therapeutic settings. Moreover, ER121 shows potential as a preventive therapy in neoadjuvant settings for erbB2-associated tumors and when administered systemically can dramatically limit erbB2 brain metastases in animal models.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11531735/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567010","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":"Transcription Factor Forkhead Box Protein 3 (FOXP3) as a Prognostic Indicator for Postoperative Outcomes in Patients with Breast Cancer: Establishment of a Prognostic Nomogram.","authors":"Chunlei Tan, Jinling Xu, Shiyuan Zhang, Shuqiang Liu, Xiaotian Yang, Danping Wu, Boqian Yu, Yuanxi Huang","doi":"10.2147/BCTT.S484055","DOIUrl":"10.2147/BCTT.S484055","url":null,"abstract":"<p><strong>Purpose: </strong>The current investigation is to assess FOXP3 expression in breast cancer patients and evaluate the predictive significance of FOXP3.</p><p><strong>Patients and methods: </strong>A cohort of 313 cases between January 2015 and November 2015 were enrolled this research. Immunohistochemistry (IHC) assay was utilized to detect the expression levels of FOXP3 in primary breast carcinoma specimens. These patients were separated into two groups by semiquantitative scoring approach. Chi-square test and Fisher's exact test were conducted to investigate the correlations between FOXP3 expression in tumors and clinicopathological variables. Kaplan-Meier method and Log rank test were utilized to generate survival curves for disease-free survival (DFS) and overall survival (OS). The independent factors were examined using Cox regression analysis. Nomogram models were created for assessing DFS and OS rates.</p><p><strong>Results: </strong>Depending on the levels of FOXP3 expression in tumors, these patients were categorized into two groups: low FOXP3 expression (174 cases) and high FOXP3 expression (139 cases). The patients exhibiting low levels of FOXP3 expression in tumors demonstrated a longer survival duration contrasted with those with high expression (DFS: 88.75 vs 65.87 months, χ²=36.1100, P<0.0001; OS: 89.70 vs 78.37 months, χ²=32.4900, P<0.0001). Multivariate analysis revealed that FOXP3 was a significant prognostic factor [DFS: hazard ratio (HR): 2.822, 95% CI: 1.595-4.992, P<0.0001; OS: HR: 3.232, 95% CI: 1.812-5.763, P<0.0001]. The good predictive clinical utility of FOXP3-based nomograms within the threshold probability range for different survival rates was demonstrated by calibration curve and decision curve analyses.</p><p><strong>Conclusion: </strong>FOXP3 expression serves as a crucial prognostic indicator in breast cancer patients, and may aid preoperative evaluation in clinical practice.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505482/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142495022","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":"Intermediate Filaments in Breast Cancer Progression, and Potential Biomarker for Cancer Therapy: A Narrative Review.","authors":"Widad Aghnia Shalannandia, Yoan Chou, Muhammad Hasan Bashari, Astrid Feinisa Khairani","doi":"10.2147/BCTT.S489953","DOIUrl":"10.2147/BCTT.S489953","url":null,"abstract":"<p><p>Intermediate filaments are one of the three components of the cytoskeletons, along with actin and microtubules. The intermediate filaments consist of extensive variations of structurally related proteins with specific expression patterns in cell types. The expression pattern alteration of intermediate filaments is frequently correlated with cancer progression, specifically with the epithelial-to-mesenchymal transition process closely related to increasing cellular migration and invasion. This review will discuss the involvement of cytoplasmic intermediate filaments, specifically vimentin, nestin, and cytokeratin (CK5/CK6, CK7, CK8/CK18, CK17, CK19, CK20, CSK1), in breast cancer progression and as prognostic or diagnostic biomarkers. The potential for drug development targeting intermediate filaments in cancer will be reviewed.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11488350/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457847","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 Potential Role of SNRPD1 Stabilized by IGF2BP2 in the Progression of Triple-Negative Breast Cancer.","authors":"Siqi Liu, Xin Sun, Na Liu, Fangcai Lin","doi":"10.2147/BCTT.S481549","DOIUrl":"https://doi.org/10.2147/BCTT.S481549","url":null,"abstract":"<p><strong>Background: </strong>Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2), an RNA-binding protein with N6-methyladenosine (m6A) reader function, is associated with the poor prognosis of various tumors, including triple-negative breast cancer (TNBC). Small nuclear ribonucleoprotein D1 polypeptide (SNRPD1), a spliceosome member, exerts diagnostic and therapeutic functions in breast cancer by regulating the cell cycle and is a potential therapeutic target. However, the interaction between IGF2BP2 and SNRPD1 in the progression of TNBC remain unclear.</p><p><strong>Objective: </strong>This study aimed to investigate the interaction between IGF2BP2 and SNRPD1 in TNBC and elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were used to detect the expression levels of SNRPD1 and IGF2BP2 in human normal breast cells (MCF10A) and TNBC cells (MDA-MB-231). MDA-MB-231 cells were transfected with SNRPD1 interference or overexpression vectors, or co-transfected with SNRPD1 interference and IGF2BP2 overexpression vectors simultaneously. Cell viability, apoptosis, and invasion were assessed using MTT, flow cytometry, and Transwell assays. RNA stability, m6A levels, and the interaction between SNRPD1 and IGF2BP2 were evaluated using qRT-PCR, methylated RNA immunoprecipitation, and RIP assays.</p><p><strong>Results: </strong>SNRPD1 was significantly up-regulated in TNBC cells, promoting cell viability and invasion while inhibiting apoptosis. IGF2BP2 was also up-regulated in TNBC cells and enhanced SNRPD1 mRNA stability via m6A modification. Furthermore, IGF2BP2 overexpression reversed the anti-tumor effect of SNRPD1 knockdown.</p><p><strong>Conclusion: </strong>IGF2BP2 and SNRPD1 were significantly highly expressed in TNBC cells. IGF2BP2 might enhance the stability and protein expression of SNRPD1 through m6A-dependent mechanisms, potentially contributing to the progression of TNBC.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457856","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":"Improved Prognosis in HER2-Low Breast Cancer Patients with Reduced Ki67 Index After Neoadjuvant Chemotherapy: A Multi-Center Retrospective Study.","authors":"Man Huang, Yudi Jin, Mengyuan Wang, Qiang Song, Yanjia Fan, Yu Zhang, Cheng Tian, Chi Zhang, Shengchun Liu","doi":"10.2147/BCTT.S478110","DOIUrl":"https://doi.org/10.2147/BCTT.S478110","url":null,"abstract":"<p><strong>Background: </strong>HER2-low breast cancer represents a distinct subgroup with unique clinical characteristics and treatment challenges. Nevertheless, it remains uncertain whether there exists a distinction in δKi67 between patients with HER2-low and HER2-zero statuses, and whether the prognosis varies among patients with differing HER2 statuses and δKi67.</p><p><strong>Methods: </strong>We conducted a multi-center retrospective study to investigate the correlation between alterations in Ki67 index following NAC and the prognosis among patients with HER2-low or HER2-zero breast cancer. 3 distinct cohorts comprising patients with HER2-negative breast cancer who underwent NAC were included. Comprehensive clinicopathological data were documented, with particular emphasis on evaluating changes in Ki67 index from baseline to post-NAC. These changes were then correlated with disease-free survival (DFS) through rigorous analysis.</p><p><strong>Results: </strong>Three cohorts, comprising 403, 315, and 72 patients respectively, were finally included. The study found that δKi67 did not show significant associations with other variables and were not identified as independent risk factors for survival. Nevertheless, across the three cohorts, following NAC, HER2-low breast cancer patients with δKi67 below the cut-off value demonstrated a better prognosis compared to those with δKi67 above the cut-off value. Additionally, their prognosis was also superior to that of HER2-zero breast cancer patients with δKi67 below the cut-off value.</p><p><strong>Conclusion: </strong>Our study demonstrates that HER2-low breast cancer patients with δKi67 values below the cut-off point after NAC are associated with improved prognosis. Monitoring δKi67 index and HER2 status may help identify patients who are likely to benefit from NAC and guide personalized treatment strategies.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11472756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457846","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":"Human Leukocyte Antigen Class I Expression and Natural Killer Cell Infiltration and Its Correlation with Prognostic Features in Luminal Breast Cancers.","authors":"Maria Vernet-Tomas, Ivonne Vazquez, Francesc Olivares, David Lopez, Jose Yelamos, Laura Comerma","doi":"10.2147/BCTT.S476721","DOIUrl":"10.2147/BCTT.S476721","url":null,"abstract":"<p><strong>Purpose: </strong>The aim of this study was to determine whether low HLA-I expression and NK cells infiltration are related to prognostic features in breast cancer, as observed in cancers in other locations and non-hormone dependent breast cancers. Particularly, we explored their relation to infiltrated axillary lymph nodes (ALNs), with the aim of finding new predictors helping to decide the extent of axillary surgery.</p><p><strong>Patients and methods: </strong>We conducted a retrospective correlational analysis of 35 breast cancers from 35 breast cancer patients showing axillary infiltration at diagnosis and with upfront surgery. HLA-I H-score and the number of NK cells x 50 high power fields (HPF) in the biopsy specimen were correlated with pathological variables of the surgical specimen: number of infiltrated ALNs, tumor size, histological type, the presence of ductal carcinoma in situ, focality, histological grade, necrosis, lymphovascular and perineural invasion, Her2Neu status, and the percentages of tumor-infiltrating lymphocytes (TILs), estrogen receptor, progesterone receptor, ki67, and p53.</p><p><strong>Results: </strong>All tumors showed hormone receptor expression and three of them Her2Neu positivity. A positive correlation (p=0.001**) was found between HLA-I H-score and TILs and Ki67 expression. HLA H-score increased with histological grade and was higher in unifocal than in multifocal disease (p=0.044 and p=0.011, respectively). No other correlations were found.</p><p><strong>Conclusion: </strong>High HLA-I H-score values correlated with features of poor prognosis in this cohort of luminal breast tumors, but not with infiltrated ALNs. This finding highlights the differences between luminal breast cancer, and cancers in other locations and non-hormone dependent breast cancers, in which low HLA-I expression tends to be associated with poor prognostic features.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463177/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387829","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":"Investigating the Correlation Between Long-Term Response in Patients with Metastatic HER2+ Breast Cancer and the Activity of Regulatory T Cells: A Retrospective Study.","authors":"Mustafa Degirmenci, Gulden Diniz, Dudu Solakoglu Kahraman, Mustafa Sahbazlar, Lokman Koral, Umut Varol, Ruchan Uslu","doi":"10.2147/BCTT.S470570","DOIUrl":"10.2147/BCTT.S470570","url":null,"abstract":"<p><strong>Background: </strong>Trastuzumab is commonly utilized in the management of metastatic HER2-positive breast cancer. Our main goal was to examine the clinical outcomes and immune markers of patients who received trastuzumab and chemotherapy treatment.</p><p><strong>Methods: </strong>Between 1995 and 2012, a total of 98 patients diagnosed with metastatic HER2-positive breast cancer were retrospectively analyzed at Ege University Hospital and Tepecik Training and Research Hospital. The clinicopathological characteristics and clinical outcomes of the patients were assessed, and the associations between response rates, survival and the immune profiles of tumor infiltrating lymphocytes were statistically evaluated.</p><p><strong>Results: </strong>The average age of patients at the time of diagnosis was 50.1±10.3 (ranging from 30 to 79) years. The mean follow-up period for all patients was 97.9±53.8 months. Among the patients, complete response was observed in 24.5%, partial response in 61.2%, and stable disease in 8.2% of cases. The average progression-free survival was 50.3±26.9 months (ranging from 1 to 163 months), and the average overall survival was 88.8±59.4 months (ranging from 12 to 272 months). After analyzing all cases, it was found that patients who were younger (p=0.006), exhibited higher CD3-positivity (p=0.041), presented with higher FOXP3-positivity (p=0.025), showed complete or at least partial response to treatment (p=0.008), and experienced a long-term response to trastuzumab (and chemotherapy) treatment had longer survival (p=0.001).</p><p><strong>Conclusion: </strong>Patients with HER2-positive breast cancer, who initially respond positively to palliative trastuzumab and chemotherapy treatment, can achieve long-term tumor remission lasting for several years.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360999","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":"Plasma Exosome miR-203a-3p is a Potential Liquid Biopsy Marker for Assessing Tumor Progression in Breast Cancer Patients.","authors":"Xin Yang, Lei Fan, Jicheng Huang, Yongjun Li","doi":"10.2147/BCTT.S478328","DOIUrl":"10.2147/BCTT.S478328","url":null,"abstract":"<p><strong>Background: </strong>Timely detection of tumor progression in breast cancer (BC) patients is critical for therapeutic management and prognosis. Plasma exosomal miRNAs are potential liquid biopsy markers for monitoring tumor progression, but their roles in BC remain unclear.</p><p><strong>Methods: </strong>In the TCGA database, we first screened for miRNAs significantly associated with BC progression by comparing miRNA expression in para-carcinoma tissues, stage I BC tissues, and stage II-III BC tissues (n = 1026). Cox regression analyses and survival analyses were performed on candidate miRNAs to explore their prognostic value (n = 848). KEGG, GO, and PPI analyses were used to identify enriched pathways associated with cancer. Finally, the potential of candidate miRNAs as liquid biopsy markers was evaluated by sequencing and analyzing plasma exosomal miRNAs from our collection of 45 BC patients (14 in stage I, 31 in stage II-III) and 5 healthy controls, combined with qRT-PCR analysis to assess the correlation of candidate gene expression in plasma exosomes and BC tissues.</p><p><strong>Results: </strong>We found that only miR-203a-3p was progressively elevated with BC progression and was associated with poor prognosis in the TCGA dataset. Its potential target genes were enriched in pathways related to tumor progression, and the downregulation of 48 of these genes was associated with poor prognosis. More importantly, plasma exosomal miR-203a-3p was also found to gradually increase with BC progression, and its expression was positively correlated with miR-203a-3p in BC tissues. This result suggests that plasma exosomal miR-203a-3p may reflect the expression of miR-203a-3p in tumor tissues and serve as a potential liquid biopsy marker for monitoring BC progressions.</p><p><strong>Conclusion: </strong>We found for the first time that elevated miR-203a-3p was associated with BC progression and poor prognosis. Our findings suggested that plasma exosomal miR-203a-3p could hold potential as a liquid biopsy marker for evaluating BC progression in patients.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416789/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280249","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":"Comparative Analysis and Future Prospects of Human Epidermal Growth Factor Receptor 2 (HER2) and Trophoblast Cell-Surface Antigen 2 (Trop-2) Targeted Antibody-Drug Conjugates in Breast Cancer Treatment.","authors":"Xiaojuan Gao, Tiansheng Bu, Wenying Wang, Ying Xu","doi":"10.2147/BCTT.S480796","DOIUrl":"10.2147/BCTT.S480796","url":null,"abstract":"<p><p>Breast cancer remains the most prevalent malignancy among women globally, presenting significant challenges in therapeutic strategies due to tumor heterogeneity, drug resistance, and adverse side effects. Recent advances in targeted therapies, particularly antibody-drug conjugates (ADCs), have shown promise in addressing these challenges by selectively targeting tumor cells while sparing normal tissues. This study provides a comprehensive analysis of two innovative ADCs targeting HER2 and Trop-2, which are critical markers in various breast cancer subtypes. These conjugates combine potent cytotoxic drugs with specific antibodies, leveraging the antigens' differential expression to enhance therapeutic efficacy and reduce systemic toxicity. Our comparative analysis highlights the clinical applications, efficacy, and safety profiles of these ADCs, drawing on data from recent clinical trials. In addition, the paper discusses the potential of these ADCs in treating other types of cancers where HER2 and Trop-2 are expressed, as well as the toxicity risks associated with targeting these antigens in normal cells. Additionally, the paper discusses novel synthetic drugs that show potential in preclinical models, focusing on their mechanisms of action and therapeutic advantages over traditional chemotherapy. The findings underscore the transformative impact of targeted ADCs in breast cancer treatment, noting significant advancements in patient outcomes and management of side effects. However, ongoing issues such as resistance mechanisms and long-term safety remain challenges. The conclusion offers a forward-looking perspective on potential improvements and the future trajectory of ADC research. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics. This study not only elucidates the current landscape of ADCs in breast cancer but also sets the stage for the next generation of oncological therapeutics, with particular attention to their broader applications and associated risks.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11416103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280246","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":"Ultra-Hypofractionated Whole Breast Radiotherapy with Automated Hybrid-VMAT Technique: A Pilot Study on Safety, Skin Toxicity and Aesthetic Outcomes.","authors":"Mariangela Boccardi, Savino Cilla, Mara Fanelli, Carmela Romano, Paolo Bonome, Milena Ferro, Donato Pezzulla, Roberto Di Marco, Francesco Deodato, Gabriella Macchia","doi":"10.2147/BCTT.S470417","DOIUrl":"10.2147/BCTT.S470417","url":null,"abstract":"<p><strong>Purpose: </strong>The most prevalent treatment-related side effect related to adjuvant radiotherapy (RT) for breast cancer is acute skin toxicity in the irradiated area. The purpose of this single-institution pilot study is to provide preliminary clinical results on the feasibility and safety of a breast ultra-hypofractionated radiation treatment delivered using an automated hybrid-VMAT technique. Skin damage was assessed both with clinical examination and objectively using a Cutometer equipment.</p><p><strong>Patients and methods: </strong>Patients received 26 Gy to the whole breast and 30 Gy to the tumoral bed in 5 fractions using an automated hybrid-VMAT approach with the option for the breath hold technique if necessary. Acute and late toxicities were clinically evaluated at baseline, 1- and 6-months after treatment using the CTC-AE v.5.0 scale. An instrumental evaluation of the skin elasticity was performed using a Cutometer^® Dual MP580. Two parameters per patient, R0 (the total skin firmness) and Q1 (the elastic recovery), were registered at the different timelines.</p><p><strong>Results: </strong>From June 2022 to January 2024, 30 patients, stage T1-T2, N0 were enrolled in the study. Four out of 30 (13.3%) patients reported G2 acute skin toxicities. At 6 months, G2 late toxicity was registered in 3 patients (10%). A total of 2160 measures of R0 and Q1 were recorded. At 1 month after treatment, no correlation was found between measured values of R0 and Q1 and clinical evaluation. At 6 months after treatment, clinical late toxicity ≥1 was strongly associated with decreased R0 and Q1 values ≥24% (p = 0.003) and ≥18% (p = 0.022), respectively.</p><p><strong>Conclusion: </strong>Ultra-hypofractionated whole-breast radiotherapy, when supported by advanced treatment techniques, is both feasible and safe. No severe adverse effects were observed at any of the different timeframes. Acute and late skin toxicities were shown to be lower in contrast to data presented in the literature.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11415599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142280250","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}