Breast Cancer : Targets and Therapy最新文献

Purpose: This study aimed to assess the frequency and prognostic significance of programmed cell death ligand 1 (PD-L1) expression and tumor-infiltrating lymphocyte (TIL) subtypes in advanced triple-negative breast cancer (TNBC).

Patients and methods: A database search was conducted to identify women with previously untreated locally recurrent inoperable or metastatic TNBC treated between January 2018 and December 2022. The inclusion criteria required formalin-fixed paraffin-embedded samples aged less than four years. PD-L1 expression was evaluated using the PD-L1 IHC 22C3 pharmDx assay, and the combined positive score (CPS) was calculated. TIL subtypes were assessed using immunohistochemical staining.

Results: The study included 150 patients, with a median age of 51.5 years. The majority of patients were younger than 65 years, postmenopausal, non-white, and had metastatic TNBC. CPS≥10 was observed in 20.9% of cases, mainly in postmenopausal women. No significant differences were found in demographic characteristics and clinicopathological variables across PD-L1 subgroups. Tumors with PD-L1 CPS≥10 had higher expression of CD3+, CD4+, and CD8+ TIL subtypes. Most patients received first-line chemotherapy, with smaller proportions undergoing second, third, and fourth-line treatments. No statistically significant differences were observed in median progression-free survival (PFS) or overall survival (OS) across PD-L1 subgroups in this cohort of chemotherapy-treated patients.

Conclusion: This study provides insights into the expression profiles of PD-L1 and TIL subtypes in advanced TNBC. The PD-L1 CPS status did not significantly affect survival outcomes, but variations in TIL subtype composition were observed based on PD-L1 CPS status.

Breast cancer, being the most common type of cancer globally, stands out as the primary malignant tumor affecting females. With the advent of breast cancer immunotherapy, inhibitors targeting immune checkpoints such as anti-PD-1 (Programmed cell death protein 1) / PD-L1 (Programmed cell death-Ligand 1) and CTLA-4 (Cytotoxic T Lymphocyte-Associated Antigen-4) have demonstrated promising outcomes for breast cancer patients across all molecular subtypes, particularly those with advanced breast cancer and triple-negative breast cancer (TNBC). Our current focus lies in accurately predicting the prognosis of breast cancer patients and the effectiveness of immunotherapy. This article provides a review of emerging biomarkers for breast cancer, encompassing immune-related markers, metabolic indicators, and potential prognosis-related markers. The primary emphasis of the article is to review immune-related tumor biomarkers in breast cancer. Our goal is to summarize relevant studies capable of forecasting breast cancer prognosis and immunotherapy effectiveness. Lastly, we delve into the future directions of breast cancer immunotherapy development.

Introduction: Previous studies have shown that the HGH1 gene is associated with poor prognosis in a variety of cancers, but its specific function and molecular mechanism in the pathological process of breast cancer remain unclear.

Methods: The relationship between expression of HGH1 and overall survival in BC patients was analyzed. Enrichment analysis of HGH1-related signaling pathways and immune infiltration was performed. BC cell lines with overexpression and knockdown of HGH1 gene were constructed to tested the proliferation, migration, invasion ability and cell apoptosis. Detected the expression of PI3K/AKT pathway in BC cells and treated it with PI3K inhibitor. The effect of HGH1 on breast cancer in vivo was observed by tumor xenograft experiment.

Results: The expression of HGH1 is significantly increased in breast cancer and related to poor prognosis. The high expression of HGH1 is related to the PI3K-Akt signaling pathway, cell cycle, cell senescence, P53 signaling pathway. Overexpression of HGH1 promotes the proliferation, migration, and invasion, and inhibits apoptosis, while its knockdown yields opposite effects. HGH1 promoted the growth of BC cells by activating the PI3K/AKT/NF-κB signaling pathway, and the use of PI3K inhibitors could attenuate the promoting effect. In vivo experiments confirmed that HGH1 promoted breast cancer growth.

Conclusion: HGH1 promotes the growth of BC cells by activating the PI3K/AKT/NF-κB signaling pathway. HGH1 may become a new indicator for evaluating the poor prognosis of BC patients and serve as a potential diagnostic biomarker and therapeutic target for breast cancer.

Triple-negative breast cancer (TNBC) is recognized as the most aggressive subtype of breast cancer and is associated with poor prognosis. Clinically, TNBC is associated with significant invasiveness, high propensity for metastasis, frequent recurrence, and unfavorable outcomes. The absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2) in TNBC renders it unresponsive to endocrine therapies and treatments that target HER2. Consequently, the current therapeutic options are primarily confined to surgical intervention, adjuvant chemotherapy, and radiotherapy. Given the considerable heterogeneity of TNBC, targeted therapies have emerged as promising avenues for treatment. Furthermore, immunotherapy has demonstrated the potential to enhance overall survival and therapeutic response in patients with TNBC. Additionally, research indicates that traditional Chinese medicine (TCM) may yield beneficial effects in the management of this cancer subtype. This review aims to consolidate recent advancements in treatment strategies for TNBC, particularly those based on molecular subtypes.

Purpose: An increasing number of breast cancer (BC) patients choose prosthesis implantation after mastectomy, and the occurrence of breast implant illness (BII) has received increasing attention and the underlying molecular mechanisms have not been clearly elucidated. This study aimed to identify the crosstalk genes between BII and BC and explored their clinical value and molecular mechanism initially.

Methods: We retrieved the data from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA), and identified the differentially expressed genes (DEG) as well as module genes using Limma and weighted gene co-expression network analysis (WGCNA). Enrichment analysis, the protein-protein interaction network (PPI), and machine learning algorithms were performed to explore the hub genes. We employed a nomogram and receiver operating characteristic curve to evaluate the diagnostic accuracy. Single-cell analysis disclosed variations in the expression of key genes across distinct cellular populations. The expression levels of the key genes were further confirmed in BC cell lines. Immunohistochemical analysis was utilized to examine protein levels from 25 patients with breast cancer undergoing prosthetic implant surgery. Ultimately, we deployed single-sample Gene Set Enrichment Analysis (ssGSEA) to scrutinize the immunological profiles between the normal and BC cohorts, as well as between the non-BII and BII groups.

Results: WGCNA identified 1137 common genes, whereas DEG analysis found 541 overlapping genes in BII and BC. After constructing the PPI network, 17 key genes were selected, and three potential hub genes include KRT14, KIT, ALB were chosen for nomogram creation and diagnostic assessment through machine learning. The validation of these results was conducted by examining gene expression patterns in the validation dataset, breast cancer cell lines, and BII-BC patients. However, ssGSEA uncovered different immune cell infiltration patterns in BII and BC.

Conclusion: We pinpointed shared three central genes include KRT14, KIT, ALB and molecular pathways common to BII and BC. Shedding light on the complex mechanisms underlying these conditions and suggesting potential targets for diagnostic and therapeutic strategies.

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.