Breast Cancer : Targets and Therapy最新文献

{"title":"Non-Luminal Disease Score for Everolimus in Patients with Hormone Receptor‑positive and Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Multicenter and Retrospective Study.","authors":"Yujing Tan, Hanfang Jiang, Xinzhu Tian, Fei Ma, Jiayu Wang, Pin Zhang, Binghe Xu, Ying Fan, Weihong Zhao","doi":"10.2147/BCTT.S493053","DOIUrl":"10.2147/BCTT.S493053","url":null,"abstract":"<p><strong>Purpose: </strong>This study aims to explore the role of the non-luminal disease score (NOLUS) for everolimus in patients with hormone receptor-positive and human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer (ABC).</p><p><strong>Methods: </strong>NOLUS has previously been established as an algorithm: NOLUS (0-100) = - 0.45 × ER(%) - 0.28 × PR(%) + 0.27 × Ki67(%) + 73. Information of cancer patients was retrospectively collected from three cancer centers in China.</p><p><strong>Results: </strong>Totally, 198 HR+/HER2- ABC patients with complete records in expression rates (%) of ER, PR and Ki67 were enrolled in the study. The expression rates (%) of ER, PR, and Ki67 were 38.8 ± 27.9 <i>versus</i> 80.9 ± 14.2 (p < 0.001), 13.9 ± 14.3 <i>versus</i> 50.2 ± 30.4 (p < 0.001), and 37.8 ± 23.6 <i>versus</i> 28.7 ± 19.9 (p = 0.04), respectively, for NOLUS-positive patients and NOLUS-negative patients. For the overall population, the median PFS was 5.8 months <i>versus</i> 5.1 months in NOLUS-positive and NOLUS-negative patients (p = 0.16, HR = 0.75, 95% CI = 0.50, 1.12). The median 1L-, 2L, and 3L-PFS was 13.9 months <i>versus</i> 11.8 months (p = 0.22, HR = 1.63, 95% CI = 0.74, 3.62), 6.7 months <i>versus</i> 3.6 months (p = 0.08, HR = 0.34, 95% CI = 0.10, 1.18), and 4.6 months <i>versus</i> 4.0 months (p = 0.81, HR = 1.07, 95% CI = 0.63, 1.79) respectively, for NOLUS-positive patients and NOLUS-negative patients.</p><p><strong>Conclusion: </strong>NOLUS-positive patients have a lower percentage of ER and PR, but a higher percentage of Ki67 index. The correlation between the benefits of everolimus and NOLUS failed to develop significance, suggesting that NOLUS may not be applicable in predicting everolimus efficacy in patients with HR+/HER2- ABC. Further research is expected.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"67-78"},"PeriodicalIF":3.3,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11774108/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057937","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":"Update on Pulmonary Toxicity Induced by New Breast Cancer Treatments.","authors":"Lorenzo Belluzzi, Giulio Martinelli, Bianca Medici, Alessandro Farina, Enrica Martinelli, Fabio Canino, Federica Caggia, Alessia Molinaro, Monica Barbolini, Fabio Tamburrano, Luca Moscetti, Federico Piacentini, Massimo Dominici, Claudia Omarini","doi":"10.2147/BCTT.S489419","DOIUrl":"10.2147/BCTT.S489419","url":null,"abstract":"<p><p>In recent years, new anticancer drugs have been investigated and approved for the treatment of breast cancer based on improved survival outcomes. However, these new treatments have specific class-related side effects. Pulmonary toxicity has been identified as an adverse event of special interest with everolimus, and is becoming an increasingly significant clinical challenge with the recent approval of trastuzumab deruxtecan. Overall, the risk of pulmonary toxicity is quite low but in some cases lung damage can be fatal. We conducted an update including the available published data regarding the incidence, mechanisms of pathogenesis, clinical presentations, and treatment of lung toxicity induced by new anticancer drugs. A literature search was performed between January and June 2024, considering papers, clinical trials, case reports, case series, meta-analyses, and systematic reviews published from January 2014 to June 2024. We also provide an algorithm for diagnosis and treatment, along with real-life cases managed at the Modena Cancer Center. Data provided here show that pulmonary toxicity is a quite frequent side effect and underline that early recognition and prompt treatment are crucial for the best outcome of patients, whose overall prognosis is being improved by the availability of these new anticancer agents.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"53-66"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11762262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045536","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":"From Pioneering Discoveries to Innovative Therapies: A Journey Through the History and Advancements of Nanoparticles in Breast Cancer Treatment.","authors":"Fatemah S Basingab, Omniah A Alshahrani, Ibtehal H Alansari, Nada A Almarghalani, Nada H Alshelali, Abeer Hamad Alsaiary, Najwa Alharbi, Kawther A Zaher","doi":"10.2147/BCTT.S501448","DOIUrl":"10.2147/BCTT.S501448","url":null,"abstract":"<p><p>Nanoparticle technology has revolutionized breast cancer treatment by offering innovative solutions addressing the gaps in traditional treatment methods. This paper aimed to comprehensively explore the historical journey and advancements of nanoparticles in breast cancer treatment, highlighting their transformative impact on modern medicine. The discussion traces the evolution of nanoparticle-based therapies from their early conceptualization to their current applications and future potential. We initially explored the historical context of breast cancer treatment, highlighting the limitations of conventional therapies, such as surgery, radiation, and chemotherapy. The advent of nanotechnology has introduced a new era characterized by the development of various nanoparticles, including liposomes, dendrimers, and gold nanoparticles, designed to target cancer cells with remarkable precision. We further described the mechanisms of action for nanoparticles, including passive and active targeting, and reviewed significant breakthroughs and clinical trials that have validated their efficacy. Current applications of nanoparticles in breast cancer treatment have been examined, showcasing clinically approved therapies and comparing their effectiveness with traditional methods. This article also discusses the latest advancements in nanoparticle research, including drug delivery systems and combination therapy innovations, while addressing the current technical, biological, and regulatory challenges. The technical challenges include efficient and targeted delivery to tumor sites without affecting healthy tissue; biological, such as potential toxicity, immune system activation, or resistance mechanisms; economic, involving high production and scaling costs; and regulatory, requiring rigorous testing for safety, efficacy, and long-term effects to meet stringent approval standards. Finally, we have explored emerging trends, the potential for personalized medicine, and the ethical and social implications of this transformative technology. In conclusion, through comprehensive analysis and case studies, this paper underscores the profound impact of nanoparticles on breast cancer treatment and their future potential.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"27-51"},"PeriodicalIF":3.3,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11761866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045535","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":"Functional Analysis and Experimental Validation of the Prognostic and Immune Effects of the Oncogenic Protein CDC45 in Breast Cancer.","authors":"Jia-Ning Zhang, Lin-Wei Li, Man-Qing Cao, Xin Liu, Zi-Lu Yi, Sha-Sha Liu, Hong Liu","doi":"10.2147/BCTT.S497975","DOIUrl":"10.2147/BCTT.S497975","url":null,"abstract":"<p><strong>Purpose: </strong>Cell division cycle protein 45 (CDC45) plays a crucial role in DNA replication. This study investigates its role in breast cancer (BC) and its impact on tumor progression.</p><p><strong>Methods: </strong>We utilized the GEO database to screen differentially expressed genes (DEGs) and conducted enrichment analysis on these genes. We established a Nomogram model based on CDC45 and other clinical indicators. Additionally, we performed protein-protein interaction (PPI) network construction, drug sensitivity analysis, and immune correlation analysis of CDC45. The function of CDC45 was further verified through cell and animal experiments.</p><p><strong>Results: </strong>CDC45 is highly expressed in most tumors, including BC. The expression level of CDC45 was significantly associated with age, sex, race, cancer stage, and molecular subtypes (all p < 0.05). CDC45 was incorporated into a Nomogram model, which showed moderate accuracy in predicting patient prognosis. We also analyzed the co-expression genes of CDC45, including TOPBP1, GINS2, MCM5, GINS1, GINS4, POLE2, MCM2, MCM6, MCM4, and MCM7. Furthermore, CDC45 expression was closely linked to immune infiltration levels, immune checkpoint inhibitors, and the therapeutic response to small molecule drugs. Finally, both in vitro and in vivo experiments confirmed the cancer-promoting effect of CDC45 in BC.</p><p><strong>Conclusion: </strong>The expression level of CDC45 is linked to the prognosis, immune infiltration, and drug sensitivity of BC. In vitro and in vivo experiments have confirmed that CDC45 acts as a cancer-promoting protein in breast cancer.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"11-25"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982592","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":"Optimizing Xenograft Models for Breast Cancer: A Comparative Analysis of Cell-Derived and Patient-Derived Implantation Techniques in Pre-Clinical Research.","authors":"Astrid Feinisa Khairani, Shella Harmonia, Yoan Chou, Nayla Majeda Alfarafisa, Julia Ramadhanti","doi":"10.2147/BCTT.S490532","DOIUrl":"10.2147/BCTT.S490532","url":null,"abstract":"<p><strong>Purpose: </strong>The high mortality rate of breast cancer motivates researchers to search for effective treatments. Due to their ability to simulate human conditions, xenograft models such as CDX (Cell line-Derived Xenografts) and PDX (Patient-Derived Xenografts) have gained popularity in pre-clinical research. The choice of xenograft technique is influenced by the type of tumor employed, particularly in more aggressive tumor models like TNBC with metastases. Subcutaneous or orthotopic implantation may influence tumor engraftment rates and the applicability of the models for drug testing. To optimize xenograft models and support the development of breast cancer drugs, selecting a suitable transplantation technique is essential to attaining the best results.</p><p><strong>Methods: </strong>This scoping review used PRISMA-Scr methodology to summarize findings from eleven articles published between 2012 and 2024 on pre-clinical trials related to xenograft models for breast cancer considering PDX began traction after 2010. Using specific criteria, the review included studies from electronic platforms. The inclusion criteria ensured relevant English sources were available in full text, while the exclusion criteria eliminated certain types of articles and inadequately comprehensive studies.</p><p><strong>Results: </strong>Subcutaneous and orthotopic implantation are critical methods for xenograft models in cancer research. Subcutaneous implantation is less invasive and more manageable but does not fully mimic the tumor's natural environment. Orthotopic implantation accurately mimic the migration, invasion, and molecular characteristics of the original tumor, although the procedure is more complex and requires specialized techniques. The specific research objectives determine their choice, the need for accurate tumor replication, and the testing convenience.</p><p><strong>Conclusion: </strong>Orthotopic implantation is the preferable method for developing PDX and CDX models of breast cancer because it closely mimics the tumor microenvironment and metastatic behavior, yielding clinically relevant results for drug testing. Subcutaneous implantation may result in higher engraftment rates, but it cannot accurately represent the complexity of tumors.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"17 ","pages":"1-10"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11727321/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982619","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":"Correlation of Histopathological and Radiological Response Patterns and Their Prognostic Implications in Breast Cancer After Neoadjuvant Chemotherapy.","authors":"Ahmet Bozer, Cengiz Yilmaz, Hülya Çetin Tunçez, Demet Kocatepe Çavdar, Zehra Hilal Adıbelli","doi":"10.2147/BCTT.S495553","DOIUrl":"https://doi.org/10.2147/BCTT.S495553","url":null,"abstract":"<p><strong>Purpose: </strong>In breast cancer (BC), neoadjuvant chemotherapy (NAC) responses can be categorized as concentric shrinkage (CS), non-concentric shrinkage (non-CS), and complete response, influencing surgical planning and survival. This study evaluates the correlation between histopathological and radiological response patterns in BC patients after NAC and their impact on overall survival (OS) and disease-free survival (DFS).</p><p><strong>Patients and methods: </strong>This retrospective study analyzed 168 BC patients who received NAC between 2018 and 2022. Tumor response was evaluated radiologically using MRI and histopathologically after surgery. Radiological response patterns were categorized into CS, non-CS, and radiological complete response (rCR). Histopathologically, patients were classified into CS, non-CS, and pathological complete response (pCR). Concordance between radiological and histopathological classifications was assessed using the kappa statistic. Survival outcomes, including OS and DFS, were analyzed using Kaplan-Meier methods.</p><p><strong>Results: </strong>Histopathological response patterns were distributed as CS (31.5%), non-CS (34.5%), and pCR (34%). Moderate agreement was observed between radiological and histopathological assessments (κ: 0.439, p < 0.001). Radiological evaluation identified 64% of CS, 50% of non-CS, and 74% of pCR cases accurately. Tumor molecular subtypes significantly correlated with both radiologic and histopathologic response patterns (p < 0.001). Subtype analysis revealed higher pCR rates in TN, HER2-enriched, and Luminal B-HER2(+) tumors, while non-CS was predominant in Luminal A tumors. No significant correlation was observed between histopathological or radiological patterns and OS (p: 0.291, p: 0.515) or DFS (p: 0.599, p: 0.899). However, patients achieving pCR tended to have better survival outcomes.</p><p><strong>Conclusion: </strong>We observed moderate concordance between histopathological and radiological response patterns in BC patients after NAC, but discrepancies highlight the limitations of radiological evaluation alone. These patterns did not significantly correlate with prognosis. Higher pCR rates were associated with better outcomes, but response patterns alone may not predict survival, warranting further research in larger cohorts.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"1005-1017"},"PeriodicalIF":3.3,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699841/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930702","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":"Quercetin Promote the Chemosensitivity in Organoids Derived from Patients with Breast Cancer.","authors":"Shengwen Meng, Yifan Cao, Lei Lu, Xuanhe Li, Siyu Sun, Fangqian Jiang, Jianfei Lu, Dongwei Fan, Xinxin Han, Tingjing Yao","doi":"10.2147/BCTT.S494901","DOIUrl":"10.2147/BCTT.S494901","url":null,"abstract":"<p><strong>Aim: </strong>The study aimed to culture organoids from tissues of patients with breast cancer (BC) and use the organoids to measure the sensitivity to quercetin and its combination with chemotherapeutic agents.</p><p><strong>Methods: </strong>Four patient-derived organoids (PDOs) of BC were cultured. The proliferative activity and morphology of PDOs were evaluated on different generations and after resuscitation. H&E and immunohistochemical (IHC) staining were used to identify the pathological changes and the expression of biomarkers. The sensitivity to quercetin and chemotherapeutic agents and their combinations were evaluated using adenosine triphosphate (ATP) viability assays.</p><p><strong>Results: </strong>We successfully obtained all PDOs from BC tissues. PDOs preserved their activity and morphology during generation passage. In addition, the pathological changes and expression patterns of estrogen receptor (ER), human epidermal growth factor receptor (HER2), and Ki67 of each PDO were consistent with their original tissues. All four PDOs were highly sensitive to quercetin, and their IC50 values were less than 22 μM. PDOs showed better sensitivity to docetaxel and epirubicin hydrochloride, but less sensitivity to cis-platinum. Combination with quercetin promoted the sensitivity to three chemotherapeutic agents. In particular, the IC50 value of cis-platinum greatly decreased.</p><p><strong>Conclusion: </strong>We successfully established PDOs from patients with BC and demonstrated that quercetin can promote the sensitivity of chemotherapeutic agents in these PDOs.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"993-1004"},"PeriodicalIF":3.3,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885139","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":"Preoperative Prediction of Breast Cancer Histological Grade Using Intratumoral and Peritumoral Radiomics Features from T2WI and DWI MR Sequences.","authors":"Yaxin Guo, Jun Liao, Shunian Li, Yiyan Shang, Yunxia Wang, Qingxia Wu, Yaping Wu, Meiyun Wang, Fengshan Yan, Hongna Tan","doi":"10.2147/BCTT.S487988","DOIUrl":"10.2147/BCTT.S487988","url":null,"abstract":"<p><strong>Background: </strong>Histological grade is an acknowledged prognostic factor for breast cancer, essential for determining clinical treatment strategies and prognosis assessment. Our study aims to establish intra- and peritumoral radiomics models using T2WI and DWI MR sequences for predicting the histological grade of breast cancer.</p><p><strong>Methods: </strong>700 breast cancer cases who had MRI scans before surgery were included. The intratumoral region (ITR) of interest was manually delineated, while the peritumoral region (PTR-3 mm) was automatically obtained by expanding the ITR by 3 mm. Radiomics features were extracted using the intra- and peritumoral images from T2WI and DWI sequences on breast MRI. Then, the key features with the strongest predictivity of histological grade were selected. Finally, 9 predictive radiomics models were established based on T2WI-ITR, T2WI-3mmPTR, DWI-ITR, DWI-3mmPTR, T2WI-ITR + 3mmPTR, DWI-ITR + 3mmPTR, (T2WI + DWI)-ITR, (T2WI + DWI)-3mmPTR and (T2WI + DWI)-ITR + 3mmPTR.</p><p><strong>Results: </strong>The (T2WI + DWI)-ITR + 3mmPTR contained 13 DWI features which included a shape feature, a texture feature, and 11 filtered features, as well as 10 T2WI features, all of which were filtered features. Among the 9 models, the combined models showed better performance than the single models in both the training and test sets, especially for the (T2WI + DWI)-ITR + 3mmPTR radiomics model. The (T2WI + DWI)-ITR + 3mmPTR radiomics model achieved a sensitivity, specificity, accuracy, and AUC of 80.4%, 72.4%, 75.0%, and 0.860 in the training set, and 68.9%, 70.5%, 70.0%, and 0.781 in the test set. Decision curve analysis (DCA) showed that the (T2WI + DWI)-ITR + 3mmPTR model had the greatest net clinical benefit compared to the other models.</p><p><strong>Conclusion: </strong>The intra- and peritumoral radiomics methodologies using T2WI and DWI MR sequences could be utilized to assess histological grade for breast cancer, particularly with the (T2WI + DWI)-ITR + 3mmPTR radiomics model demonstrating significant potential for clinical application.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"981-991"},"PeriodicalIF":3.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11668253/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885134","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 History of Breast Cancer Early Detection: 1865 - 2020.","authors":"Frank E Gump, Priyanka Parmar, Sheldon Feldman, Anjuli M Gupta","doi":"10.2147/BCTT.S476416","DOIUrl":"10.2147/BCTT.S476416","url":null,"abstract":"<p><p>Early detection is a relative newcomer in medicine, with its efficacy relying not only on therapy but also on the availability of evidence supporting the advantage of treatment at an earlier stage. Late 19th century histologic evidence that cancer begins as a single primary focus and Halsted's centrifugal theory of stepwise spread (breast, regional nodes, and systemic distribution) provided the rationale for both en bloc surgery and the lifesaving benefit of early detection. Clinicians soon noticed exceptions to this ordered timeline, and pathologists identified histological features that questioned its primacy; however, Bernard Fisher spearheaded the initial challenge. His groundbreaking hypothesis that breast cancer was systemic from its inception was supported indirectly by the 3rd arm of National Surgical Adjuvant Breast and Bowel Project (NSABP) B04 and B06. These trials bolster his contention that a patient's fate was dependent on shed cells rather than the extent of the operation; however, the breast cancer wars of the 1970s focused on competing local treatments. When follow-up data revealed equivalent survival results, it established lumpectomy/radiation as equal to mastectomy, but overlooked Fisher's attack on Halsted's theory. Two mid-20th century medical innovations also played a role in the history of early detection: population-based screening by detecting cancer before it became clinically evident, and repurposing systemic treatment designed for metastatic recurrence into adjuvant chemotherapy. This review illustrates how these advances have led to the incremental acceptance of Fisher's hypothesis and recognition that invasive cancer cannot be equated with localized disease, regardless of how early it might be detected.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"973-980"},"PeriodicalIF":3.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11663696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881112","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":"A Prospective Tumour Marker for Breast Cancer: YWHAB and Its Role in Promoting Oncogenic Phenotypes.","authors":"Vaishnavi L Gopaul, Lacey Winstone, Beatrice G Gatien, Braydon D Nault, Sujit Maiti, Reid M Opperman, Mousumi Majumder","doi":"10.2147/BCTT.S479384","DOIUrl":"10.2147/BCTT.S479384","url":null,"abstract":"<p><strong>Background: </strong>YWHAB (14-3-3 Beta) was found in the secretome of miR-526b and miR-655 overexpressed breast cancer (BRCA) cell lines. The potential of YWHAB as a therapeutic target or biomarker for BRCA is investigated here.</p><p><strong>Methods: </strong>After YWHAB was knocked down with siRNA, BRCA cell lines were used for in vitro assays (proliferation, migration, epithelial-to-mesenchymal transition). In silico analysis and in situ validation with BRCA plasma and biopsy tissues were used to test YWHAB's biomarker potential.</p><p><strong>Results: </strong>YWHAB RNA and protein expression are elevated in aggressive BRCA cell lines, and the knockdown of YWHAB inhibited cell migration, proliferation, and EMT in all subtypes of tumour cell lines. YWHAB expression is significantly higher in BRCA biopsy tissue and blood plasma compared to control tissues and benign plasmas. YWHAB is expressed in all hormonal subtypes of BRCA tumours and has shown increased expression in advanced tumour stages. Its high expression is linked to poor patient survival. YWHAB is a sensitivity tumour marker (AUC of 0.7340, p = 0.0012) but is not a promising blood biomarker. Nevertheless, combined with pri-miR-526b, YWHAB mRNA expression shows potential as a BRCA blood biomarker (AUC of 0.711, p = 0.032), which must be validated in a larger sample set.</p><p><strong>Conclusion: </strong>We elucidate the novel role of YWHAB as a therapeutic target in BRCA, given that its inhibition mitigated aggressive phenotypes across all tumour subtypes, including triple-negative breast cancer. Furthermore, <i>YWHAB</i> emerges as a potential tumour marker, exhibiting high expression in metastatic BRCA and correlating with poor patient survival; however, it is not a sensitive blood biomarker.</p>","PeriodicalId":9106,"journal":{"name":"Breast Cancer : Targets and Therapy","volume":"16 ","pages":"935-956"},"PeriodicalIF":3.3,"publicationDate":"2024-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11656333/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142863394","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}