Breast Cancer : Targets and Therapy最新文献

Background: This study investigated the relationship between Shear Wave Elastography (SWE), TGF-β1/MAPK signaling molecules, and epithelial-to-mesenchymal transition (EMT) in breast lesions, exploring the feasibility of SWE in early EMT identification for breast cancer.

Methods: 117 breast lesions in 107 patients from July to November 2023 were consecutively enrolled. SWE was performed preoperatively, and elastic parameters were documented. Immunohistochemistry (IHC) assessed the expression levels of TGF-β1, p38 MAPK, p-p38 MAPK, ERK1/2, p-ERK1/2, ERK5, p-ERK5, JNK, p-JNK, E-cadherin, β-catenin, N-cadherin, and Vimentin. Correlations between SWE parameters and biomarkers were analysed, and their diagnostic efficacy for axillary lymph node metastasis (LNM) was evaluated.

Results: Among 117 breast lesions, 53 were classified as benign and 64 as malignant (25 exhibiting axillary LNM). Optimal SWE thresholds for distinguishing benign from malignant lesions were Emax = 106.7 kPa, Emean = 62.9 kPa, Emin = 22.5 kPa, Eratio = 3.4, and Esd = 21.2 kPa. For LNM prediction, cut-offs were Emax = 170.1 kPa, Emean = 118.5 kPa, and Eratio = 10.5. TGF-β1 and E-cadherin showed significant predictive value for LNM (AUCs: 0.774 and 0.704, respectively). E-cadherin negatively correlated with SWE parameters, while TGF-β1 and MAPK molecules (p38 MAPK, p-p38 MAPK) showed positive correlations. Lesions with "stiff rim sign" had significantly lower E-cadherin expression but elevated levels of TGF-β1 (P<0.001). Additionally, Vimentin, p38 MAPK and p-p38 MAPK levels were higher in the occurrence of the "stiff rim sign" (P all <0.05).

Conclusion: TGF-β1, p38 MAPK, and E-cadherin demonstrated strong diagnostic capabilities and correlated with SWE parameters. SWE offers a promising non-invasive approach for assessing prognosis by identifying EMT characteristics at an earlier stage in breast cancer.

Triple-negative breast cancer (TNBC) has become the most aggressive and worst prognostic subtype of breast cancer due to the lack of estrogen receptor, progesterone receptor and HER2 expression. This article systematically reviews the progress in the diagnosis, prognosis and treatment of TNBC. In terms of diagnosis, imaging techniques (such as dynamic contrast-enhanced MRI and multimodality ultrasound) combined with histological and immunohistochemical detection (such as Ki-67, PD-L1 expression) can improve the early diagnosis rate; molecular markers (PIM-1, miR-522) and subtype classification (LAR, IM, BLIS, MES) provide the basis for accurate classification. Prognostic evaluation requires a combination of clinicopathologic features (tumor size, lymph node metastasis, tumor-to-stroma ratio), molecular characteristics (BRCA mutation, PD-L1 expression), and prognostic scoring systems. In treatment strategies, chemotherapy remains the basis, but efficacy and side effects need to be balanced; neoadjuvant chemotherapy can improve the pathological complete response rate, while molecular markers (such as circulating tumor cells) help predict efficacy. In terms of targeted therapy, PARP inhibitors are significantly effective in patients with BRCA mutations, and antibody drug conjugates (eg, sacituzumab govitecan) provide new options for chemoresistant patients. In immunotherapy, PD-1/PD-L1 inhibitors combined with chemotherapy significantly improved progression-free survival, especially for PD-L1-positive patients. Combined therapy, metabolic reprogramming, and individualized treatment strategies need to be further explored in the future to overcome the heterogeneity and treatment resistance of TNBC. This article emphasizes the key role of multidisciplinary collaboration and precision medicine in optimizing TNBC management and provides an important reference for clinical practice and research direction.

Purpose: We aimed to identify genetic alterations in groups with different HER2 immunohistochemical (IHC) scores.

Patients and methods: A total of 120 patients with HER2-positive breast cancers, including 89 cases with IHC 3+ tumors and 31 cases with IHC 2+ and positive for in situ hybridization (ISH) were enrolled. Molecular profiles were determined using Thermo Fisher TMO comprehensive assay on surgically removed tissues. All called variants were compared between IHC3+ and IHC2+/ISH+ groups by Fisher exact test.

Results: There was a significantly higher sample frequency 94.4% (84/89) of ERBB2 amplification in IHC3+ group than that in IHC2+/ISH+ group 45.2% (14/31). By contrast, there was a significantly lower sample frequency of MYC_AMP_CNA 10.1% (9/89) and CCND3_AMP_CNA 0% (0/89) in IHC3+ group than those in IHC2+/ISH+ group with sample frequency 25.8% (8/31), and 9.7% (3/31), respectively.

Conclusion: We conclude that HER2 IHC3+ tumors have higher frequency of ERBB2_ AMP_CNA and lower frequency of CCND3_ AMP_CNA and MYC_AMP_CNA than IHC2+/ISH+ tumors. These results provide therapeutic strategies in treatment of HER2-positive breast cancer.

Background: The study aimed to explore the tissue morphology and hemodynamics of rabbit VX2 breast carcinoma by high-frequency ultrasound (US) and the effectiveness and safety of US-guided percutaneous microwave coagulation (PMC) therapy on rabbit VX2 breast tumors.

Methods: Twenty VX2 tumor-bearing rabbits were assessed using color Doppler ultrasound for tumor growth characteristics including echo, size, blood supply and hemodynamic parameters once a week for six weeks. Subsequently, US-guided PMC was performed in randomly assigned ten VX2 tumor-bearing rabbits (the other ten as controls). US images after ablation were obtained and analyzed. Three rabbits with double VX2 tumors were used as pathological observation at weeks 0, 1, and 4 of ablation. The therapeutic efficacy was evaluated by tumor growth, physical examinations, survival time, survival rate and metastasis of tumors and histopathology.

Results: Ultrasound monitoring indicated that the tumor growth rate was 463.09% at the 2^nd to 3^rd weeks, and PMC was performed during this period under real-time US guidance. After microwave ablation, some tumors were greatly reduced or undetectable at week 8. Moreover, no flow signals were detected by US. The survival rates at 2 and 3 months in the treatment group and control group were 100%, 70% and 10%, 0%, respectively, while the metastatic rates were 10%, 30% and 90%, 100%, respectively (P<0.05).

Conclusion: The proliferation and metastasis of rabbit VX2 breast carcinoma were monitored by US imaging, and US-guided percutaneous microwave ablation was proven to be a safe, effective and minimally invasive therapeutic option for treating breast cancer in rabbits, showing potential clinical applicability.

Objective: Telomere maintenance mechanism significantly impacts the metastasis, progression, and survival of breast cancer (BC) patients. This study aimed to investigate the role of telomere maintenance-related genes (TMRGs) in BC prognosis and to construct a related prognostic model.

Methods: Differentially expressed genes were identified from the TCGA-BC cohort, and functional enrichment analysis was conducted. TMRGs were sourced from the literature and intersected with DEGs. Candidate genes were selected using machine learning algorithms, including Lasso Cox, Random Forest, and XGBoost. Multivariate Cox regression analysis was conducted to construct a prognostic model and identify hub genes. Subsequent analyses included survival analysis, gene set enrichment analysis (GSEA), immune infiltration analysis, and drug sensitivity analysis of the hub genes. Finally, in vitro experiments were conducted to validate the expression of the hub genes.

Results: A total of 1329 differentially expressed TMRGs were analyzed, with 128 significantly associated with overall survival. Machine learning identified 7 prognosis-related TMRGs: MECP2, PCMT1, PFKL, PTMA, TAGLN2, TRMT5, and XRCC4. These genes were used to construct a prognostic model, with MECP2, PCMT1, PFKL, TAGLN2, and XRCC4 as harmful factors, while PTMA and TRMT5 were protective. The model demonstrated a significant prognostic value (AUC: 0.81, 0.72, 0.69 for 1-, 3-, and 5-year, respectively). Survival analysis confirmed the prognostic relevance of these genes, and GSEA highlighted their roles in oxidative phosphorylation, glycolysis, and PI3K/AKT/mTOR signaling.

Conclusion: The study identified 7 key TMRGs with significant prognostic value in BC. The constructed model effectively stratifies patient risk, providing a foundation for targeted therapies and personalized treatment strategies.

Background: Tumor-associated macrophages (TAMs) constitute an important part of the tumor microenvironment of breast cancer (BC), and they play an essential role in modulating tumor growth and invasion. However, the role of TAMs in neoadjuvant chemotherapy (NAC) has not been fully elucidated. Therefore, the aim of this study was to assess the function of TAM subtypes and investigate their role in the response to NAC in BC.

Methods: Presence of TAMs was examined immunohistochemically (IHC) in pre- and post- NAC treatment tumor tissue in a cohort of 138 BC patients. IHC staining with monoclonal antibodies for CD68 and CD163 were performed. Positivity was defined as staining > 1% TAMs in stroma and tumor cell nests. Response to NAC was evaluated according to tumor size change and Residual Cancer Burden (RCB) index.

Results: CD68+ and CD163+ TAMs decreased significantly in both the stroma and tumor nests (TN) after NAC. The median CD68+ TAMs in the stroma decreased significantly from 5% to 1% (p < 0.005), while CD163+ TAMs showed a marked reduction from 20% to 5% (p < 0.001). Post-NAC, the persistence of CD68+ and CD163+ TAMs in the stroma was strongly correlated with larger residual tumor size (p < 0.005 and p < 0.001, respectively). Changes in CD163+ TAM levels in the stroma were significantly associated with RCB classes (p < 0.005). Pre-NAC, CD163+ TAMs in the stroma and TN showed a significant association with TILs; however, no correlations with TILs were observed post-NAC.

Conclusion: This study highlights the critical role of TAMs dynamics in shaping NAC response in BC. Notably, CD163+ TAMs may emerge as pivotal players in mechanisms of chemotherapy resistance and response, underscoring their potential as biomarkers and therapeutic targets in breast cancer treatment.

Purpose: This study efforts to explore the association of adverse events (AEs) with efficacy in HER2-positive breast cancer patients treated with TDM1.

Methods and materials: This retrospective study included women diagnosed with HER2+ BC treated with TDM1 from January 2012 to December 2023. Event-free survival (EFS) was the endpoint. Tumour response was assessed by disease control rate (DCR) and objective response rate (ORR). The chi-squared test, analysis of variance (ANOVA), Cox proportional hazards regression and Kaplan-Meier survival analysis was employed to evaluate the association of AEs with tumour efficacy.

Results: A total of 48 women with a median age of 52 years (median follow-up 8.4 months) were included in the study. Among them, 33 patients (68.8%) experienced adverse events, including platelet depletion and liver function abnormalities, 3 patients (6.3%) discontinued TDM1 due to severe platelet depletion. The overall objective response rate (ORR) was 25.0% and the disease control rate (DCR) was 43.8%. Using the Chi-squared test, we found a statistically significant difference in ORR and DCR between patients who developed a platelet reduction and those who did not. DCR was significantly higher in patients with liver dysfunction than in those without. ANOVA showed that exposure to hepatic dysfunction and platelet reduction, lines of therapy, and treatment course were associated with EFS. In the Kaplan-Meier survival analysis, both liver dysfunction and platelet reduction were correlated with significantly longer EFS (p=0.033 and p=0.038, respectively).

Conclusion: This retrospective study demonstrated that AEs were associated with tumour efficacy in patients with HER2+ BC treated with TDM1.

Introduction: Breast cancer is the most prevalent malignancy worldwide which carries a high mortality rate. Quality of life (QoL) is adversely affected by the disease process; thus, this systematic review aimed to Summarize the QoL among women with breast cancer in Saudi Arabia, and descriptively analyze the risk factors that are associated with low QoL.

Methods: Following the PRISMA guidelines for systematic review, a literature search for all cross-sectional studies conducted in Saudi Arabia was performed in five databases including PubMed, DOAJ, Scopus, Google Scholar, and Mendeley, then, the studies which met the eligibility criteria were extracted and assessed for quality using AXIS tool.

Results: Following a full-text evaluation, there were a total of 8 included articles. Based on the EORTC QLQ-C30 questionnaire, the Global Health Status (GHS) score of patients with breast cancer ranged from 31.2 +20 to 73.16 ± 20.26. Elements that impact Health Related Quality of Life (HRQol) are the age of breast cancer diagnosis, marital status, and number of children. Women who are childless, widowed, or divorced have a lower quality of life (QoL), and those who were diagnosed beyond the age of 50 have worse emotional functioning. Emotional well-being is lowered by the coexisting medical issues especially if living alone. Chemotherapy and monoclonal antibodies can make the patients stressed and more tired. Rehabilitation groups surprisingly can increase insomnia, while immunotherapy and radiation therapy may decrease physical function, particularly in older patients.

Conclusion: This systematic review has identified several factors that affect the quality of life of breast cancer patients in Saudi Arabia, including physical, mental, functional, and social well-being, as well as various sociodemographic factors. Understanding these factors and implementing a QoL assessment tool in clinical practice can aid in the development of supportive measurements for those patients and their families, helping them to manage their life challenges more effectively.

Background: Accurate identification of the molecular subtypes of breast cancer is essential for effective treatment selection and prognosis prediction.

Aim: This study aimed to evaluate the diagnostic performance of a radiomics model, which integrates breast mammography and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in predicting the molecular subtypes of breast cancer.

Methods: We retrospectively included 462 female patients with pathologically confirmed breast cancer, including 53 cases of triple-negative, 94 cases of HER2 overexpression, 95 cases of luminal A, and 215 cases of luminal B breast cancer. Radiomics analysis was performed using FAE software, wherein the radiomic features were examined about the hormone receptor status. The performance of the model was evaluated using the area under the receiver operating characteristic curve (AUC) and accuracy.

Results: In multivariate analysis, radiomic features were the only independent predictive factors for molecular subtypes. The model that incorporates multimodal fusion features from breast mammography and DCE-MRI images exhibited superior overall performance compared to using either modality independently. The AUC values (or accuracies) for six pairings were as follows: 0.648 (0.627) for luminal A vs luminal B, 0.819 (0.793) for luminal A vs HER2 overexpression, 0.725 (0.696) for luminal A vs triple-negative subtype, 0.644 (0.560) for luminal B vs HER2 overexpression, 0.625 (0.636) for luminal B vs triple-negative subtype, and 0.598 (0.500) for triple-negative subtype vs HER2 overexpression.

Conclusion: The radionics model utilizing multimodal fusion features from breast mammography combined with DCE-MRI images showed high performance in distinguishing molecular subtypes of breast cancer. It is of significance to accurately predict prognosis and determine treatment strategy of breast cancer by molecular classification.

Background: Breast cancer (BC) has become the main malignant tumor threatening the health of women worldwide. Previous studies have reported that Lactate dehydrogenase-A (LDHA) has critical roles in cancer development and progression. We aimed to explore the roles of LDHA and LDH5 isoenzyme activity in BC, which provides a new insight into LDHA for the treatment of BC.

Methods: The expression of LDHA in BC and its relationship with clinicopathological features were obtained from various databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), Breast Cancer-Gene Expression Miner (bc-GenExMiner), TNMplot, UALCAN. The Kaplan‒Meier Plotter was used to evaluate the prognostic value of LDHA. Western blot was performed to detect LDHA expression. Agarose gel electrophoresis was performed to detect the activities of LDH isoenzymes. The in vitro proliferation, migration and invasion potentials of BC cells were evaluated using MTT assays, colony formation, wound-healing assay, matrix metalloproteinase assays and transwell assays, respectively. The activities of LDH isoenzymes in serum and tissues were measured in patients with BC and healthy controls.

Results: Compared to normal tissues, LDHA expression was significantly higher in BC tissues. Patients' nodal status, histological types, TP53 mutation status and PAM50 subtypes were significant factors influencing the LDHA expression. By overexpressing or silencing LDHA gene in BT549 cells, it was confirmed that LDHA promoted cell proliferation, migration and invasion. LDH5 isoenzyme activity in patients with BC was higher than healthy controls. The increased activity of LDH5 isoenzymes was induced by overexpression of LDHA in BC. High expression of LDHA was found to be associated with poor prognosis in BC.

Conclusion: LDHA plays a critical role in the progression of BC through the regulation of the activity of LDH5 isoenzyme, indicating that LDHA may serve as a valuable target for BC treatment.