Breast Cancer : Targets and Therapy最新文献

Breast cancer remains the leading malignancy in terms of morbidity and mortality today. The tumor microenvironment of breast cancer includes multiple cell types, secreted proteins, and signaling components such as exosomes. Among these, exosomes have a lipid bilayer structure. Exosomes can reflect the biological traits of the parent cell and carry a variety of biologically active components, including proteins, lipids, small molecules, and non-coding RNAs, which include miRNA, lncRNA, and circRNA. MiRNAs are a group of non-coding RNAs of approximately 20-23 nucleotides in length encoded by the genome, triggering silencing and functional repression of target genes. MiRNAs have been shown to play a significant role in the development of cancer owing to their role in the prognosis, pathogenesis, diagnosis, and treatment of cancer. MiRNAs in exosomes can serve as effective mediators of information transfer from parental cells to recipient cells and trigger changes in biological traits such as proliferation, invasion, migration, and drug resistance. These changes can profoundly alter the progression of breast cancer. Therefore, here, we systematically summarize the association of exosomal miRNAs on breast cancer progression, diagnosis, and treatment in the hope of providing novel strategies and directions for subsequent breast cancer treatment.

Purpose: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subgroup characterized by a high risk of resistance to chemotherapies and high relapse potential. TNBC shows inter-and intra-tumoral heterogeneity; more than half expresses high EGFR levels and about 30% are classified as HER2-low breast cancers. High PRMT5 mRNA levels are associated with poor prognosis in TNBC and inhibiting PRMT5 impairs the viability of subsets of TNBC cell lines and delays tumor growth in TNBC mice models. TNBC patients may therefore benefit from a treatment targeting PRMT5. The aim of this study was to assess the therapeutic benefit of combining a PRMT5 inhibitor with different chemotherapies used in the clinics to treat TNBC patients, or with FDA-approved inhibitors targeting the HER family members.

Methods: The drug combinations were performed using proliferation and colony formation assays on TNBC cell lines that were sensitive or resistant to EPZ015938, a PRMT5 inhibitor that has been evaluated in clinical trials. The chemotherapies analyzed were cisplatin, doxorubicin, camptothecin, and paclitaxel. The targeted therapies tested were erlotinib (EGFR inhibitor), neratinib (EGFR/HER2/HER4 inhibitor) and tucatinib (HER2 inhibitor).

Results: We found that PRMT5 inhibition synergized mostly with cisplatin, and to a lesser extent with doxorubicin or camptothecin, but not with paclitaxel, to impair TNBC cell proliferation. PRMT5 inhibition also synergized with erlotinib and neratinib in TNBC cell lines, especially in those overexpressing EGFR. Additionally, a synergistic interaction was observed with neratinib and tucatinib in a HER2-low TNBC cell line as well as in a HER2-positive breast cancer cell line. We noticed that synergy can be obtained in TNBC cell lines that were resistant to PRMT5 inhibition alone.

Conclusion: Altogether, our data highlight the therapeutic potential of targeting PRMT5 using combinatorial strategies for the treatment of subsets of TNBC patients.

Triple negative breast cancer (TNBC) is a subtype of breast cancer which does not express or expresses a minimum amount of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor 2 (HER2) protein. TNBCs include a heterogenic group of cancers that are aggressive, grow rapidly and are associated with poor prognosis and overall survival, mainly attributed to a lack of effective therapeutic targets. For a long time, a major issue with predicting the outcome and prognosis of TNBCs was the lack of an accurate biomarker, a molecule that helps us objectively assess a patient's health status. In recent times, defining the presence of tumor-infiltrating lymphocytes (TIL) is becoming an indispensable method of determining a patient's prognosis. TILs are found in tumor tissue and the surrounding stroma and carry a prognostic value. Furthermore, they are known to improve the effect of systemic therapy. With the rise of immunotherapy, the role of TIL in this newer therapeutic option is a topic of increased importance. The goal behind this research article is a comprehensive review of the current literature on the importance of tumor-infiltrating lymphocytes in the prognosis of TNBC.

Postmastectomy pain syndrome (PMPS) is a common and debilitating form of postsurgical pain with neuropathic characteristics, presenting as burning, stabbing, or pulling sensations after mastectomy, lumpectomy, or other breast procedures. With a prevalence of 31%, the risk factors for PMPS include younger age, psychosocial factors, radiotherapy, axillary lymph node dissection, and a history of chronic pain. This review evaluates the pharmacological and surgical options for managing PMPS. Pharmacological treatment options include antidepressants, gabapentinoids, levetiracetam, capsaicin, and topical lidocaine. Procedural and surgical options include fat grafting, nerve blocks, radiofrequency ablation, peripheral nerve surgery, serratus plane block, and botulinum toxin injections. Despite the variety of therapeutic options available for patients, further randomized trials are required to conclude whether these treatments reduce the intensity of neuropathic pain in patients with PMPS. In particular, comparative studies and the inclusion of patients across a range of pain intensities will be essential to developing a treatment algorithm for PMPS. In conclusion, current management for these patients should be tailored to their individual requirements.

A total of 18% of global breast cancer (BC) deaths are attributed to BC in China, making it one of the five most common cancers there. There has been a steady rise in BC morbidity and mortality in women in the last few years and it is now a leading cancer among Chinese women. Conventional treatments for BC are currently effective but have several limitations and disadvantages, and Traditional Chinese medicine (TCM) plays a vital role in the overall process of cancer prevention and therapy. It is known that TCM can treat a variety of conditions at a variety of sites and targets. In recent years, increasingly, research has been conducted on TCM's ability to treat BC. TCM has shown positive results in the treatment of breast cancer and the adverse effects of radiotherapy and chemotherapy. This review describes the progress of clinical observation and mechanism research of TCM in the treatment of breast cancer in recent years. It provides some ideas and theoretical basis for the treatment of BC with TCM.

Purpose: Programmed cell death ligand 1 (PDL1) has the predictive and prognostic value in a great deal of cancers. This study aims to explore the expression of PDL1 in stage III breast cancer (BC) and its correlation with clinical outcome.

Methods: The protein expression of PDL1 in tumor tissues was determined by immunohistochemistry (IHC). The correlations between PDL1 and clinicopathological variables were performed by χ²-tests or Fisher's exact tests. The Cox proportional hazards model was used for univariate and multivariate analysis of the potential prognostic factors. Survival curves were estimated based on Kaplan-Meier analyses, and Log Rank test was used to contrast factors influencing the survival outcome.

Results: On the basis of the semiquantitative scoring method for PDL1 expression, the patients were divided into low PDL1 expression group (109 cases) and high PDL1 expression group (107 cases). PDL1 expression was correlated with positive lymph nodes, positive axillary lymph nodes, postoperative radiotherapy, and CK5/6 expression (P < 0.05). The PDL1 expression in tumor tissues was discovered to be a potential prognostic risk factor with the disease-free survival (DFS) and overall survival (OS) for stage III BC. Moreover, patients with high PDL1 expression showed longer lifetime (DFS and OS) compared to those with low PDL1 expression in total patient population (P < 0.05). Moreover, the nomogram showed that the prediction line is in good agreement with the reference line for postoperative 1-, 3-, and 5-year lifetime. The DCA curve showed that the 3- and 5-year lifetime by nomogram had so much better divination of the clinical application than only by PDL1.

Conclusion: PDL1 is a latent prognostic factor in stage III BC and is closely related to some clinicopathological features. PDL1 expression in tumor tissues is significantly associated with better lifetime rate in stage III BC.

Breast cancer is the most commonly diagnosed cancer and the leading cause of death among female patients, which seriously threatens the health of women in the whole world. The treatments of breast cancer require the cooperation of a multidisciplinary setting and taking tumor load and molecular makers into account. For early breast cancer, breast-conserving surgery with radiotherapy or mastectomy alone remains the standard management, and the administration of adjuvant systemic therapy is decided by the status of lymph nodes, hormone receptors, and human epidermal growth factor receptor-2. For metastatic breast cancer, the goal of treatments is to prolong survival and maintain quality of life. This review will present the current advances and controversies of surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, gene therapy, and other innovative treatment strategies in early-stage and metastatic breast cancer.

Background: Histological grade is an important prognostic factor for patients with breast cancer and can affect clinical decision-making. From a clinical perspective, developing an efficient and non-invasive method for evaluating histological grading is desirable, facilitating improved clinical decision-making by physicians. This study aimed to develop an integrated model based on radiomics and clinical imaging features for preoperative prediction of histological grade invasive breast cancer.

Methods: In this retrospective study, we recruited 211 patients with invasive breast cancer and randomly assigned them to either a training group (n=147) or a validation group (n=64) with a 7:3 ratio. Patients were classified as having low-grade tumors, which included grade I and II tumors, or high-grade tumors, which included grade III tumors. Three models were constructed based on basic clinical features, radiomics features, and the sum of the two. To assess diagnostic performance of the radiomics models, we employed measures such as receiver operating characteristic (ROC) curve, decision curve analysis (DCA), accuracy, sensitivity, and specificity, and the predictive performance of the three models was compared using the DeLong test and net reclassification improvement (NRI).

Results: The area under the curve (AUC) of the clinical model, radiomics model, and comprehensive model was 0.682, 0.833, and 0.882 in the training set and 0.741, 0.751, and 0.836 in the validation set, respectively. NRI analysis confirmed that the combined model was better than the other two models in predicting the histological grade of breast cancer (NRI=21.4% in the testing cohort).

Conclusion: Compared with the other models, the comprehensive model based on the combination of basic clinical features and radiomics features exhibits more significant potential for predicting histological grade and can better assist clinicians in optimal decision-making.

Background: This study aimed to analyze the specific expression of hsa_circ_0007823 in triple-negative breast cancer (TNBC) and explore the roles and related molecular mechanisms of hsa_circ_0007823 in TNBC.

Materials and methods: Relative hsa_circ_0007823 levels in TNBC tissues and cell lines were examined by reverse transcription-quantitative polymerase chain reaction. The value of hsa_circ_0007823 levels was evaluated in patients' clinicopathological characteristics and prognostic prediction. A dual-luciferase reporter assay was used to determine the relationship between hsa_circ_0007823, miR-182-5p, and FOXO1. The effect of circ_0007823 overexpression on the growth of TNBC cells was investigated in vitro and in vivo.

Results: Lower levels of hsa_circ_0007823 were found in TNBC tissues and cell lines and were closely associated with lymph node metastasis, poorer overall and disease-free survival rates. MiR-182-5p was significantly up-regulated, whereas FOXO1 was down-regulated in TNBC cell lines. The miR-182-5p inhibition up-regulated FOXO1 in TNBC cells. Dual-luciferase reporter assays showed that hsa_circ_0007823, miR-182-5p, and FOXO1 interacted with each other. Overexpression of circ_0007823 significantly inhibited the viability, migration, and invasion of TNBC cell lines, but promoted apoptosis. In vivo experiments showed that circ_0007823 overexpression inhibited tumor growth and down-regulated miR-182-5p and up-regulated FOXO1.

Conclusion: Hsa_circ_0007823 overexpression could suppress the growth, invasion, and migration of TNBC cells, and inhibit tumor growth by regulating miR-182-5p/FOXO1.

Aim: To investigate the impact of DIBH for heart sparing effect on left sided breast postoperative whole breast irradiation by comparing the dosimetric characteristics of 3D-CRT hybrid VMAT and pure VMAT treatment planning under DIBH condition.

Materials and methods: The primary CT data sets from previously treated left sided early breast cancer were used for pure volumetric arc therapy (VMAT) technique re-planning for the dosimetric characteristics comparison. A treatment plan of 3D-CRT hybrid VMAT technique was re-planned on the free breath (FB) condition for the investigation of the dosimetric characteristics comparison on DIBH condition. The prescribed dose for all the treatment plans was 42.5Gy in 16 fractions. All plans were optimized to cover 100% of the PTV by 95% of prescribed dose. The dosimetric differences among the 3 treatment plans for the 20 patients were analyzed using Wilcoxon signed-rank test, with p value<0.05 considered statistically significant.

Results: 3D-CRT hybrid VMAT using DIBH technique yielded the best results on the conformity index (CI) and homogeneity index (HI). By comparing this 3D-CRT hybrid VMAT technique using FB and DIBH technique, the mean heart dose (MHD) was reduced from 5.38Gy to 1.65Gy, respectively (p =0.001) and the left anterior descending coronary artery (LAD)0.03cc dose was reduced from 27.87Gy to 9.41Gy, respectively (p =0.001). 3D-CRT hybrid VMAT using DIBH technique significantly reduced the V5, V20 and D mean of the ipsilateral lung and D mean of the contralateral lung. The D5 of right breast was significantly reduced by 3D-CRT hybrid VMAT compared with VMAT using DIBH technique.

Conclusion: The incorporation of DIBH into 3D-CRT hybrid VMAT technique provides the best benefits for the heart and the OAR with respect to the radiation dose-sparing effect without compromising the target conformity and homogeneity in the treatment planning.