Search

Breast cancer is a malignant tumor that predominantly affects women. The incidence of breast cancer has risen annually and is increasingly occurring in younger population, posing a significant threat to women’s health. Estrogen receptor-positive breast cancer is the most prevalent subtype, accounting for 75% of all cases. Endocrine therapy, particularly with tamoxifen, serves as the primary treatment for these subtypes. However, due to the highly heterogeneous nature of breast cancer, some patients remain at risk for recurrence even after undergoing tamoxifen treatment. Therefore, it is essential to investigate the mechanism of tamoxifen in breast cancer treatment from a single-cell perspective. In comparison to single-cell genomics and single-cell proteomics, single-cell metabolomics can offer a clearer representation of the chemical changes occurring within individual cells by measuring the end products of cellular activity—metabolites. Thus, this approach can provide a more direct reflection of the differences between cells. In this study, single-cell mass cytometry was employed to investigate metabolite alterations in MCF-7 cells upon exposure to tamoxifen, aiming to elucidate its mechanism from a single-cell perspective. The 3-(4,5-dimethylthiazol-2-yl)-5-(3- carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was utilized to assess the impact of tamoxifen on MCF-7 cell proliferation and established optimal conditions for subsequent therapies involving these cells. The results showed that 576 metabolites under positive ion mode and 480 metabolites under negative ion mode are identified by using single-cell mass cytometry approach. In total, 811 metabolites are detected in MCF-7 cells without tamoxifen treatment compared to 776 metabolites identified following tamoxifen administration. It demonstrated that metabolites observed under negative ion mode effectively distinguish between MCF-7 cells treated with and without tamoxifen. Exposure to tamoxifen can result in upregulation of 28 metabolites and downregulation of 59 metabolites, and these changes predominantly influence metabolic pathways including taurinehypotaurine metabolism, caffeine metabolism, cysteine-methionine metabolism, glycine-serinethreonine metabolism, purine metabolism, starch-sucrose metabolism, and pyrimidine metabolism. The findings indicated that the intervention of the aforementioned metabolites and metabolic pathways may represent one of the mechanisms through which tamoxifen exerts its effects against estrogen receptor-positive breast cancer. This study employed single-cell metabolomics based on mass spectrometry to explore the metabolic alterations in breast cancer cells induced by tamoxifen, which is often overlooked in metabolomics studies based on bulk cells. Furthermore, it elucidates the mechanism of tamoxifen’s action against estrogen receptor-positive breast cancer from a single-cell metabolomic perspective, thereby provides valuable insights for understanding the mechanisms underlying other therapeutic agents. [ABSTRACT FROM AUTHOR]

Objective To analyze whether there is a threshold effect between thyroid hormone sensitivity indexes and breast cancer, and to analyze the subgroup analysis and interaction test of age. Methods 2 892 adults from NHANES were collected between 2007 and 2012, including 83 breast cancer patients. Central thyroid hormone sensitivity indices were calculated, including Thyroid Feedback Quantile Index for T4(TFQIFT4) and T3(TFQIFT3), Thyroid Stimulating Hormone T4 Resistance Index(TT4RI), Thyroid Stimulating Hormone T3 Resistance Index(TT3RI), and TSH Index(TSHI), as well as peripheral thyroid hormone sensitivity index FT3/FT4. The association between breast cancer and the thyroid system was investigated using a multivariable logistic regression model. Smooth curve fitting and stratified analysis were used too, and subgroup analysis and interaction tests were performed based on age. Results Model3 showed that Thyroid Stimulating Hormone (TSH) (OR=1.33, 95%CI:1.08-1.63), TFQIFT4(OR=2.61, 95%CI:1.25-5.45), TFQIFT3(OR=3.15, 95%CI:1.18-8.44), TT4RI(OR=1.03, 95%CI:1.01-1.05), TT3RI(OR=1.10, 95%CI:1.03-1.18), and TSHI(OR=1.68, 95%CI:1.14-2.50) were significantly positively associated with the risk of breast cancer. A linear relationship with breast cancer was observed when TFQIFT3≥0.7, TSHI≥2.4, and TT4RI<50(P<0.05). TFQIFT4 showed a threshold effect(likelihood ratio test=0.040) when TFQIFT4<0.25. The relationship between TFQIFT4 and breast cancer was not significant(OR=1.07, 95%CI:0.36-3.15), but when TFQIFT4≥0.25, it was significantly associated with an increased risk of breast cancer(OR=12.79, 95%CI:2.50-65.40). Subgroup analysis further revealed that in women over 55 years old, increased central thyroid hormone sensitivity indices were associated with breast cancer risk(P<0.05). Conclusion Increased central thyroid hormone sensitivity indices are significantly associated with the risk of breast cancer, which may be a potential indicator for breast cancer detection in the future. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical, psychological, and economic impacts of the initial dressing change timing following peripherally inserted central catheter (PICC) placement in postoperative breast cancer patients. Methods We enrolled a total of 120 patients who underwent PICC placement following breast cancer surgery at a tertiary hospital in Guangzhou between April and October 2023 for this study. Based on predefined inclusion and exclusion criteria, the patients were divided into an observation group and a control group, with each group comprising 60 patients. In the observation group, the first dressing change was performed 48 hours after PICC placement, whereas in the control group it was done within 24 hours post-placement. The primary outcomes assessed included pain intensity at the puncture site during the initial dressing change, occurrence of bleeding at the puncture site within one week, psychological state evaluated using validated scales such as PHQ-9 depression scale and GAD-7 anxiety scale, as well as maintenance frequency and associated costs over a three-week period. Results There were no significant differences in baseline characteristics between the two groups. The observation group exhibited significantly lower pain levels at the puncture site during the initial dressing change, reduced bleeding at the puncture site within one week, and a shorter duration of bleeding compared to the control group (P < 0.001). Moreover, the observation group demonstrated statistically significant decreases in depression and anxiety scores, as well as maintenance frequency and costs within three weeks post-placement when compared to the control group (P < 0.001). Conclusions The implementation of an early dressing change within 48 hours after PICC catheterization in breast cancer patients undergoing surgery has been demonstrated to effectively ameliorate hemorrhage and discomfort at the puncture site, consequently mitigating patient distress and anxiety. Moreover, this intervention facilitates a decrease in dressing change frequency while reducing financial burdens on patients. [ABSTRACT FROM AUTHOR]

Endocrine therapy is the most important adjuvant treatment for early estrogen receptor (ER)-positive breast cancer. ER-low-positive (immunohistochemistry staining 1%-10%) breast cancer has drawn widespread attention in recent years. This group accounts for 3%-9% of overall breast cancer patients. The efficacy of endocrine adjuvant therapy is relatively limited in patients with ER-low-positive breast cancer. Although the proportion of patients with low ER expression in breast cancer population is relatively low, the clinical needs of this population can not be ignored because of the large number of breast cancer patients. A number of studies have suggested that ER-low-positive breast cancer is different from ER-positive breast cancer, and is similar to ER-negative breast cancer in terms of molecular and biological characteristics, clinical features and prognosis. There are still controversies on the benefit and duration of endocrine therapy for early ER-low-positive breast cancer, and there is a lack of evidence from large-scale prospective studies. Multiple retrospective studies and meta-analyses have suggested that ER-low-positive breast cancer may have limited benefit from adjuvant endocrine therapy, and therefore endocrine therapy should be considered with caution in this population. The benefit of adjuvant therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors is yet to be supported by future data Some patients with ER-low-positive breast cancer may try adjuvant chemotherapy in consideration of other risk factors. Additionally, clinical trials that test antibody-drug conjugates (such as sacituzumab govitecan and Dato-DXd), poly (ADP-ribose) polymerase (PARP) inhibitors, and immunotherapies for the treatment of early ER-low-positive breast cancer are still ongoing, including the phase Ⅲ ASCENT-05 study evaluating the adjuvant therapy of sacituzumab govitecan combined with pembrolizumab in highrisk human epidermal growth factor receptor 2 (HER2)-negative, ER and progesterone receptor (PR)<10% patients after surgery, the phase Ⅲ SASCIA study evaluating the adjuvant therapy of sacituzumab govitecan in high-risk HER2-negative patients after surgery, and the phase Ⅲ TROPION-Breast 04 study evaluating the neoadjuvant therapy of Dato-DXd combined with durvalumab. In addition, a neoadjuvant treatment for triple-negative breast cancer (TNBC) and ER-low expression breast cancer with olaparib and durvalumab (NCT03594396) is being explored, and the results are worth expecting. This article aimed to introduce the definition, clinical and pathological characteristics, and prognosis of ER-low breast cancer, and expound on the current treatment status and potential therapeutic strategies for HER2-negative, ER-low-positive early breast cancer in the future. [ABSTRACT FROM AUTHOR]

Background and purpose: Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA special binding protein that participates in regulating the expression of related genes and protein translation. It has been linked to the malignant occurrence and development of various tumors, but its role in breast cancer remains unclear. The aim of this study was to investigate the effects of hnRNPK on ferroptosis in breast cancer cells and the underlying mechanisms. Methods: Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, hnRNPK expression in breast cancer tissues and normal tissues and its relationship with clinical prognosis were analyzed by bioinformatics. We detected hnRNPK expression in breast cancer cells and tissues using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry staining diagnosis methods. MCF-7 and MDA-MB-231 breast cancer cells were transfected with siRNA, and divided into control group (control), empty body group (NC), and interference vector group (si-hnRNPK). Cell proliferation was detected by cell counting kit-8 (CCK-8) and plate clone formation assays. RNA-seq analysis was applied to explore potential targeted biological functions and signaling pathways affected by hnRNPK. Additionally, we investigated the impact of hnRNPK on ferroptosis phenotype using Western blot and commercial kits for reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe2+, ferroptosis inhibitor (ferrostatin-1, Fer-1) was used to detect the rescue effect of hnRNPK knockdown on ferroptosis. The impact of hnRNPK on the expressions of Wnt/β-catenin pathway-related proteins were determined by Western blot. Results: The bioinformatics analyses indicated hnRNPK was upregulated in breast cancer tissues (P＜0.01), and the overall survival of patients in the high expression group was poorer compared with those in the low expression group (P＜0.05). hnRNPK was highly expressed in breast cancer tissues and cells, and knocking down hnRNPK weakened the proliferation ability of breast cancer cells (P＜0.05). The RNA-seq analysis showed that hnRNPK was significantly enriched in ferroptosis, apoptosis, and the Wnt/β-catenin signaling pathway. Knocking down hnRNPK promoted ferroptosis in breast cancer cells by inducing lipid ROS and MDA, as well as Fe2+ accumulation (P＜0.05). Interestingly, the ferroptosis inhibitor ferrostatin-1 (Fer-1) reversed the promotive effect of hnRNPK knockdown on ferroptosis (P＜0.05). Downregulation of hnRNPK led to a decrease in the expressions of β-catenin and c-Myc in the Wnt/β-catenin signaling pathway, while expressions of CK1α, APC and the GSK-3β complex were elevated (P＜0.05). Conclusion: hnRNPK is highly expressed in breast cancer, and knocking down hnRNPK promotes ferroptosis in breast cancer cells by inhibiting the Wnt/β-catenin signaling pathway, thereby suppressing the malignant progression of breast cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: Human epidermal growth factor receptor 2 (HER2) serves as one of the paramount drivers of breast cancer metastasis, with roughly 20%-30% of breast cancer patients exhibiting high expression of HER2. The expression level of HER2 is regulatable at multiple molecular levels and determines the metastatic potential of breast cancer cells; however, the manner in which HER2 expression is modulated at the mRNA level remains ambiguous. Circ-0007766 is a circRNA originated from the coding gene ERBB2 for HER2, and whether circ-0007766 can regulate HER2 expression via the ceRNA mechanism has not been reported. This study aimed to analyze whether circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2 expression. Methods: In this study, a high-throughput circRNA chip was employed to screen for circRNAs that exhibited highly specific expression in HER2-positive breast cancer cells. RNA fluorescence in situ hybridization (FISH) was utilized to detect the subcellular localization of circ-0007766. The BaseScope experiment was conducted to analyze the expression level of circ-0007766 in breast cancer tissues and its clinical diagnostic significance. Breast cancer cell models with overexpression and knockdown of circ-0007766 were constructed by transfecting cloning plasmids and siRNA in vitro. The effect of circ-0007766 on the migration and invasion of breast cancer cells was assessed using transwell migration and invasion experiments, and the migration and invasion abilities of MDA-MB-231 and SK-BR-3 cells were measured. Additionally, it was evaluated whether circ-0007766 could promote the migration and invasion of breast cancer cells through miR-1972. A dual luciferase reporter gene assay was used to verify whether circ-0007766 could regulate HER2 expression by binding to miR-1972. The direct interaction between circ-0007766 and miR-1972 was further verified through the RAP experiment. RIP detection was performed in MDA-MB-231 cells, and the relative 3'UTR of HER2 mRNA was measured by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Western blot was used to detect the protein expressions. Results: Circ-0007766 was conspicuously highly expressed in HER2-positive breast cancer cells and distributed in both the cytoplasm and nucleus of cells, with the preponderance being in the cytoplasm. The expression level of circ-0007766 was strikingly higher in breast cancer tissues than in para-cancerous tissues. The expression of circ-0007766 was significantly elevated in HER2-positive breast cancer samples compared with HER2-negative samples. The overexpression (knockdown) of circ-0007766 in HER2-negative breast cancer cells (in HER2-positive breast cancer cells) was capable of promoting (inhibiting) the migration and invasion of breast cancer cells. Circ-0007766 directly bound to miR-1972, which inhibited breast cancer cell migration and invasion, thereby forming an endogenous competitive RNA (ceRNA) regulatory network and impeding the downregulation of HER2 mRNA and protein expression mediated by miR-1972. Circ-0007766 could potentiate the inhibitory effect of miR-1972 on HER2-mediated breast cancer cell migration and invasion that was negatively regulated by miR-1972. CircRNAs sequestered miRNAs to function as ceRNAs, thereby regulating gene expression at both the transcriptional and translational levels. Finally, we discovered that the expressions of circ-0007766 and HER2 were positively correlated in breast cancer cell and tissue samples, while the expression levels of miR-1972 and HER2 were negatively correlated. Circ-0007766 could specifically target miR-1972 to hinder its regulatory effect on HER2 expression. Conclusion: This study discovers that circ-0007766 facilitates the migration and invasion of breast cancer cells via the miR-1972/HER2 signal axis, offering a novel biomarker and potential therapeutic target for patients with metastatic HER2-positive breast cancer. [ABSTRACT FROM AUTHOR]

Background and purpose: Breast cancer is a major global public health problem. Bone is the most common site of distant metastasis of breast cancer, accounting for about 70% of all metastatic cases. Bone metastasis of breast cancer can cause a series of complications, including severe pain, pathological fracture, hypercalcemia, spinal cord compression, etc., which bring great inconvenience to patients' physical activities and affect their quality of life. Metastatic recurrence is the leading cause of death in breast cancer patients. Therefore, there is an urgent need to build a diagnostic model of bone metastasis in breast cancer to identify patients with a high risk of bone metastasis. The aim of this study was to develop a predictive model based on machine learning to predict the probability of breast cancer developing bone metastasis. Methods: Data of breast cancer patients diagnosed between 2010 and 2015 were extracted from The Surveillance, Epidemiology, and End Results (SEER) database. The variables were screened by least absolute shrinkage and selection operator (LASSO) regression, univariate and multivariate logistic regression analysis, and statistically significant risk factors were included to build a prediction model. In this study, nine machine learning algorithms, including decision tree, elastic network, K-nearest neighbor, lightweight gradient elevator, logistic regression, neural network, random forest, support vector machine and limit gradient lifting, were used to adjust the model hyperparameters through random search and 5x cross-validation to build a breast cancer bone metastasis prediction model. The area under the receiver operating characteristic (ROC) curve, calibration curve and decision curve were used to evaluate the model, the optimal model was obtained, and the importance of variables was analyzed based on the optimal model. Finally, a network calculator for predicting the risk of bone metastasis of breast cancer was established using the optimal model. Results: The study included 10 106 patients with breast cancer, 7 073 patients in the training set, and 3 033 patients in the validation set. We found that 4 494 (63.5%) patients in the training set and 1 927 (63.5%) patients in the validation set developed bone metastases, respectively. Race, pathologic grade, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, N stage, lung metastasis, radiotherapy, chemotherapy and surgery were independent predictors of bone metastasis. The training set and verification set were used to verify the model, and the limit gradient lifting algorithm was superior to other machine learning algorithms by integrating the evaluation indexes such as the area under the ROC curve, calibration curve and decision curve. Finally, we used limit gradient algorithm to build network calculator for prediction of breast cancer bone metastases (https://bcbm.shinyapps.io/DynNomapp/). Conclusion: This study developed a predictive model based on machine learning to predict the probability of bone metastases in breast cancer patients, hoping to help clinicians make more rational treatment decisions. [ABSTRACT FROM AUTHOR]

Progesterone, also known as luteinizing hormone, is a crucial physiological hormone that regulates the menstrual cycle, reproduction, and the biosynthesis of steroid hormones, playing a vital role in addressing human fertility issues. This paper vividly introduces progesterone and its derivatives through anthropomorphic language, highlighting their significant roles in women's lives, including the menstrual cycle, contraception mechanisms, pregnancy, and breast cancer treatment. The aim is to enhance understanding of the physiological effects of progesterone and to encourage reflection on life and health. [ABSTRACT FROM AUTHOR]

To search, evaluate and integrate the best evidence for the management of drug⁃related symptoms during endocrine therapy in breast cancer patients, so as to provide reference for clinical practice. Methods According to the "6S" model of evidence⁃based resources, computer⁃aided literature search was conducted on BMJ Best Practice, Up To Date, Website of World Health Organization (WHO), Guidelines International Network (GIN), PubMed, CNKI, and Wanfang Database. The types of literature covered guidelines, systematic review/Meta⁃analysis, evidence summary, clinical decision⁃making, and expert consensus. The search period was from the establishment of the database to April 2023. Two evidence⁃based professionals evaluated the quality of the included literatures and extracted the data. Results A total of 16 references were included, including 3 clinical decision⁃makings, 2 guidelines, 1 expert consensus, and 10 systematic reviews. A total of 27 pieces of the best evidence of drug ⁃ related symptom management in endocrine therapy for breast cancer patients were summarized with respect to 6 aspects, including risk assessment, individualized management, general symptom management strategy, drug intervention, non⁃drug intervention, and cognitive behavioral intervention. Conclusions The 27 pieces of summarized evidence can be used for the symptom management of drug⁃related side effects in endocrine therapy in breast cancer patients, and specific evidence should be selected according to cultural background, clinical situation, patient's symptoms and willingness. [ABSTRACT FROM AUTHOR]

Objective To investigate the clinical efficacy of pedicled latissimus dorsi myocutaneous flap in repairing breast soft tissue defects. Methods A retrospective analysis was conducted on seven female patients, who underwent latissimus dorsi flap surgery for breast soft tissue defects at Shunde Hospital of Guangzhou University of Chinese Medicine from October 2017 to March 2024. The size of the soft tissue defects ranged from 6.0 cm×6.0 cm to 18.0 cm×10.0 cm. The latissimus dorsi myocutaneous flap was used for repair, and the donor site was closed by primary suture. The size of the flaps ranged from 8.0 cm×8.0 cm×0.5 cm to 22.0 cm×12.0 cm×1.5 cm. Patients were followed up for observation of healing, temperature, sensation, and appearance at both donor and recipient sites. Results All seven patients were followed up for a period ranging from 2 to 12 months, during which all flaps and skin grafts survived. Six cases showed good healing with linear scars at the donor site after primary suture closure; one case experienced marginal skin necrosis but recovered well after skin grafting with a satisfactory appearance.In this study, the prognosis of trauma was evaluated by the efficacy satisfaction scale, in which 7 cases the trauma was healed, in 5 cases the flap morphology was close to normal, in 7 cases the flap sensation was present, in 6 cases the flap temperature was normal, and in 7 cases the dorsal donor area was free of obvious scarring. The patients' satisfaction scores ranged from 7.0 to 10.0, with a mean of 9.0. Conclusion Pedunculated latissimus dorsi flap is a reliable method for repairing breast soft tissue defects due to its high practicality, fewer complications and higher success rate. [ABSTRACT FROM AUTHOR]

Objective To analyze the impact of endoscopy surgery and open surgery on the quality of life of breast cancer patients. Methods Three hundred and forty-four female breast cancer patients who underwent two different surgical methods were collected, including 92 cases in the endoscopic surgery group and 252 cases in the open surgery group. Functional Assessment of Cancer Therapy-Breast (FACT-B) was used to investigate the quality of life of patients after surgery in two groups. Results The FACT-B items“I am satisfied with my sex life”“I am able to work (including home work) ”“My work (including home work) makes me feel a sense of accomplishment”“I feel sexually attractive”“I still feel like a woman”“I worry about the effect of stress on my disease”were statistically significant in two groups (all P < 0.05), the endoscopic surgery group was superior to the open surgery group. There was no significant difference in the other items between the two groups (all P > 0.05) . Conclusion The quality of life of breast cancer patients undergoing endoscopy surgery was better than that of patients undergoing open surgery. [ABSTRACT FROM AUTHOR]

Objective To explore the clinical value of anti-Müllerian hormone (AMH) to optimize endocrine therapy for peri-menopausal early breast cancer. Methods Two hundred and four patients of pre-menopausal breast cancer aged 45-55 years old between 2020 and 2023 were enrolled, and AMH≤ 0.1 ng/mL was considered as cut-off value for menopause. Switching from selective estrogen receptor modulator (SERM) to aromatase inhibitor aromatase inhibitor (AI) and initial endocrine therapy regimens were based on AMH, follicle-stimulating hormone (FSH) and estradiol (E2). Results Pre-chemotherapy AMH level was significantly negatively correlated with FSH level (P<0.001). Among 100 cases who were amenorrhea for one year during SERM treatment, 42 cases did not have AMH testing. Fourteen out of the 42 cases switched to AI within one year, and ovarian function recovery (OFR) occurred in 2 cases after AI switching. Fifteen cases with AMH>0.1 ng/mL did not switch to AI within one year. Forty among 43 cases with AMH≤0.1 ng/mL switched to AI, after a significantly shorter median SERM treatment duration (3.15 months vs. 8.14 months, P<0.001) and a significantly lower OFR rate (0 vs. 12.5%, P=0.023) compared with those who did not test AMH but switched to AI. AMH≤0.1 ng/mL was an independent risk factor of transition to menopause shortly in peri-menopausal patients (OR=35.857, P< 0.001). Among 104 cases with AMH tested before adjuvant chemotherapy, 69 cases had AMH>0.1 ng/mL. Thirty-one out of the 69 cases were treated with ovarian function suppression (OFS) initially and 38 with SERM initially. Thirty-five cases with AMH≤0.1 ng/mL were all treated with SERM initially, with a higher rate of switching to AI(71.4% vs. 23.7%, P<0.001) and a shorter SERM treatment duration(6.52 months vs. 13.56 months, P=0.016) compared with the 38 cases (AMH>0.1 ng/mL) treated initially with SERM. After a median 30-month follow-up, no recurrence was observed in these thirty-five cases treated with SERM initially and AMH≤0.1 ng/mL, just like in OFS group. And they had a tendency of improved survival outcome compared with those treated with SERM initially and AMH>0.1 ng/mL (Log Rank P=0.076). Conclusion AMH could evaluate and predict menopause accurately, resulting in optimizing endocrine therapy for peri-menopausal patients effectively and safely. [ABSTRACT FROM AUTHOR]

Neutrophils originate from the bone marrow, differentiating from hematopoietic stem cells, and are the most prevalent polymorphonuclear leukocytes in the blood, accounting for approximately 70% of the total white blood cells in adult peripheral blood. Neutrophils are recognized as one of the relatively short-lived cells in the body, with a normal half-life of just a few hours in the peripheral blood, which rely on continuous replenishment from the bone marrow to maintain the number. As short-lived effectors of the innate immune system, neutrophils participate in various inflammatory and immune processes, and constitute the first line of defense against infection, playing a crucial role in the activation and regulation of both innate and adaptive immunity. Neutrophils were once considered as key effectors of inflammation and infection. Because of their short lifespan and non-proliferative nature, the role of neutrophils in cancer was overlooked. Their role in cancer has been increasingly recognized in recent years. However, more and more studies demonstrate that neutrophils play a much more significant role in cancer than previously thought. Breast cancer is one of the common malignant tumors in women, and its morbidity and mortality are in the forefront of female malignant tumors. The incidence of breast cancer is rising globally, posing a severe threat to the physical and mental health of women worldwide. Recent studies confirm that tumor-associated neutrophils (TANs) have become a critical component of the tumor microenvironment (TME) and play a significant role in the development, progression and metastasis of breast cancer. TANs are formed via the interaction of various tumor-derived cytokines which stimulate and recruit neutrophils to accumulate in the TME. The strong plasticity and diversity of neutrophils endow TANs with dual potential to both promote and inhibit tumors. TANs advance breast cancer progression by promoting tumor growth and metastasis, supporting tumor angiogenesis, immune suppression, and generating neutrophil extracellular traps (NETs). Conversely, TANs mediate antitumor responses through direct tumor cell killing and contributing to the formation of antitumor immune network. Research on TANs-related breast cancer therapies, particularly in triple-negative breast cancer (TNBC), has become a research hotspot. This review summarized recent advances in the origin, formation, classification and function of TANs in breast cancer, as well as a detailed discussion of their clinical relevance. We further combined recent clinical studies to systematically summarize the treatment strategies targeting TANs in breast cancer, with the aim of providing new insights into the functional mechanisms of TANs and the treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Objective·To develop a machine learning approach for early identification of metabolic syndromes associated with inflammatory metabolic state changes in breast cancer patients after neoadjuvant therapy, using common laboratory and transthoracic echocardiography indices. Methods·Female patients with primary invasive breast cancer diagnosed at the Department of Breast Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, between September 2020 and September 2022, were included. General patient information, laboratory test results, and transthoracic echocardiography data were collected. After feature extraction, five machine learning algorithms, including random forest (RF), gradient boosting (GB), support vector machine (SVM), K-nearest neighbor (KNN), and decision tree (DT), were applied to construct a prediction model for the changes of the patients′ metabolic state after neoadjuvant therapy, and the prediction performances of the five models were compared. Results·A total of 232 cases with valid clinical data were included, comprising 135 cases before neoadjuvant therapy and 97 cases after completing 4 cycles of neoadjuvant therapy. Feature extraction identified five key features: white blood cell count, hemoglobin, high-density lipoprotein (HDL), interleukin-2 receptor, and interleukin-8. In the multi-feature analysis, the area under the receiver operating characferistic curve (AUC) was higher in the combination of white blood cell count, hemoglobin and HDL compared to the combination of interleukin-2 receptor and interleukin-8 (RF: 0.928 vs 0.772, GB: 0.900 vs 0.792, SVM: 0.941 vs 0.764, KNN: 0.907 vs 0.762, DT: 0.799 vs 0.714). The RF, SVM, and GB models showed higher AUC (0.928, 0.941, 0.900) and accuracy (0.914, 0.897, 0.776). The SVM model exhibited superior accuracy in the training data compared to the RF and GB models (P=0.394, 0.122 and 0.097, respectively). Conclusion·The SVM model can be used to establish a prediction model for identifying breast cancer patients at high risk of developing inflammatory metabolic state-related metabolic syndrome after neoadjuvant therapy by incorporating five common clinical indicators, namely, white blood cell count, hemoglobin, high-density lipoprotein, interleukin-2 receptor, and interleukin-8. SVM modeling may be useful for clinicians to establish individualized screening protocols based on a patient′s inflammatory metabolic state. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common cancers of females and is a leading cause of tumor-related death in women. Negative emotion frequently presents in patients like anxiety and depression and chronic stress which may lead to depression is a major risk factor of the cancer development. Stress leads to dysfunctions of cells, molecules and neural circuits, thus promoting depression. Chronic stress promotes the occurrence and development of breast cancer through related neurotransmitters and also affects the prognosis of breast cancer patients. [ABSTRACT FROM AUTHOR]

Objective To establish breast cancer organoids for a long time and to characterize their molecular expression and test their sensitivity to chemotherapy drugs. Methods Breast cancer specimens were digested with collagenase to release cancer cells for organoid culture. The organoids were characterized by morphology and ER, PR, HER-2, CK expression by technology of histoimmunofluorescence. Among them, three were tested for paclitaxel, doxorubicin and cisplatin sensitivity. Results A total of 44 cases of breast cancer organoids were established, all of which showed dense spherical-like growth and ER, PR, HER-2, CK, matching their clinical counterpart. Breast cancer organoids were sensitive to chemotherapy drugs paclitaxel, doxorubicin and cisplatin. Conclusions Organoid model, as a new in vitro may reproduce the pathophysiology features with heterogeneity. [ABSTRACT FROM AUTHOR]

AIM: This study explores how the combination of rapamycin (Rapa) and flagellin (FliC) affects the inhibition of 4T1 breast cancer cells. The approach involves using mRNA high-throughput sequencing to examine the underlying mechanisms of this combination therapy in vitro. METHODS: 4T1 breast cancer cells were divided into four groups: control group, Rapa group, FliC group, and Rapa+FliC group. The changes in cell viability and apoptosis were detected by the CCK-8 method and flow cytometry. Concurrently, the KEGG pathway of differentially expressed genes (DEGs) was analyzed by high-throughput mRNA sequencing. Furthermore, the DEGs between the Rapa+FliC group and Rapa groups were analyzed using STRING. The PPI network of DEGs was then constructed, and the Hub genes were subsequently screened. The protein expression of the Hub gene was verified based on the HPA database. RESULTS: CCK-8 assays and flow cytometry analysis revealed that the combination of Rapa and FliC significantly increased both the inhibition and apoptosis rates in 4T1 breast cancer cells compared to the rates observed with Rapa or FliC alone (P<0. 05). Transcriptome sequencing indicated 579 DEGs between the Rapa group and the control group, predominantly in the PI3K/ Akt signaling pathway. In contrast, DEGs between the FliC group and control were mainly concentrated in signaling pathways like NOD-like receptor signaling. Additionally, 150 DEGs were identified between the Rapa+FliC group and the Rapa group, focusing primarily on pathways such as mTOR. From the protein-protein interaction (PPI) network, ten hub genes, including Atm and Itga2, were identified. CONCLUSION: The combination of Rapa+FliC could inhibit the viability of 4T1 breast cancer cells in vitro and promote apoptosis, potentially through the PI3K/Akt/mTOR signaling pathway. The genes Atm and Itga2 could be pivotal in mediating the joint effect of this combination therapy. [ABSTRACT FROM AUTHOR]

Objective To compare the efficacy of trastuzumab plus pertuzumab (HP) combined with either nab-paclitaxel plus carboplatin or docetaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer in real-world clinical practice. Methods Clinical data of HER2-positive breast cancer patients who received neoadjuvant therapy with either HP combined with nab-paclitaxel plus carboplatin or HP combined with docetaxel plus carboplatin and subsequently underwent surgery were retrospectively collected from 11 tertiary grade-A hospitals in Hebei Province from June 2019 to December 2021. The total pathological complete response (tpCR) rates of the two groups were compared. Results A total of 76 patients were included in the study, with 47 in the nab-paclitaxel group and 29 in the docetaxel group. The tpCR rate was significantly higher in the nab-paclitaxel group than that in the docetaxel group (72.3% vs. 48.3%, χ² =4.463, P=0.035). Subgroup analysis indicated that patients older than 40 years, with cN2-3, cTNM stage Ⅲ, hormone receptor-positive status, and Ki67>30% had significantly higher tpCR rates in the nab-paclitaxel group than those in the docetaxel group (P<0.05). Conclusion In real-world clinical practice, the efficacy of HP combined with nab-paclitaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer is superior to that of HP combined with docetaxel plus carboplatin. [ABSTRACT FROM AUTHOR]

Objective: To investigate the expression of structural maintenance of chromosome 4 (SMC4) in breast cancer and its prognostic value. Methods: The expression of SMC4 gene in breast cancer tissues and its correlation with the clinicopathological characteristics of patients were analyzed using the TIMER, GEPIA, UALCAN and GEO databases. The expression of SMC4 protein in breast cancer and adjacent normal tissues was detected using immunohistochemical (IHC) staining. Correlations between SMC4 expression and clinicopathological features of breast cancer were evaluated. The relationship between SMC4 expression and survival of patients with breast cancer was evaluated by Kaplan-Meier, GEPIA database, Cox proportional hazards regression model. Results: Bioinformatics analysis showed that the mRNA level of SMC4 in breast cancer tissues was significantly higher than that in normal adjacent tissues (P < 0.01), and was closely related to clinical stage, lymph node metastasis and chemotherapy resistance (all P < 0.05). IHC staining showed that the positive and strong positive rates of SMC4 in breast cancer tissues were significantly higher than those in normal adjacent tissues (all P < 0.05). The high protein expression of SMC4 was closely related to the age, clinical stage and lymph node metastasis of breast cancer patients (all P < 0.05). The cumulative survival rate of patients in SMC4 low expression group was significantly higher than that in the SMC4 high expression group, especially in patients with HER2+ breast cancer (P < 0.05). Additionally, SMC4 is an independent risk factor for prognosis in patients with breast cancer. Conclusion: SMC4 is highly expressed in breast cancer tissues. High SMC4 expression is closely related to lymph node metastasis, clinical stage, and prognosis of patients with breast cancer, making it a potential marker for the diagnosis and prognosis of breast cancer. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Shenyang Pharmaceutical University is the property of Shenyang Pharmaceutical University and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Breast cancer is a malignant tumor that predominantly affects women. The incidence of breast cancer has risen annually and is increasingly occurring in younger population, posing a significant threat to women’s health. Estrogen receptor-positive breast cancer is the most prevalent subtype, accounting for 75% of all cases. Endocrine therapy, particularly with tamoxifen, serves as the primary treatment for these subtypes. However, due to the highly heterogeneous nature of breast cancer, some patients remain at risk for recurrence even after undergoing tamoxifen treatment. Therefore, it is essential to investigate the mechanism of tamoxifen in breast cancer treatment from a single-cell perspective. In comparison to single-cell genomics and single-cell proteomics, single-cell metabolomics can offer a clearer representation of the chemical changes occurring within individual cells by measuring the end products of cellular activity—metabolites. Thus, this approach can provide a more direct reflection of the differences between cells. In this study, single-cell mass cytometry was employed to investigate metabolite alterations in MCF-7 cells upon exposure to tamoxifen, aiming to elucidate its mechanism from a single-cell perspective. The 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay was utilized to assess the impact of tamoxifen on MCF-7 cell proliferation and established optimal conditions for subsequent therapies involving these cells. The results showed that 576 metabolites under positive ion mode and 480 metabolites under negative ion mode are identified by using single-cell mass cytometry approach. In total, 811 metabolites are detected in MCF-7 cells without tamoxifen treatment compared to 776 metabolites identified following tamoxifen administration. It demonstrated that metabolites observed under negative ion mode effectively distinguish between MCF-7 cells treated with and without tamoxifen. Exposure to tamoxifen can result in upregulation of 28 metabolites and downregulation of 59 metabolites, and these changes predominantly influence metabolic pathways including taurine-hypotaurine metabolism, caffeine metabolism, cysteine-methionine metabolism, glycine-serine-threonine metabolism, purine metabolism, starch-sucrose metabolism, and pyrimidine metabolism. The findings indicated that the intervention of the aforementioned metabolites and metabolic pathways may represent one of the mechanisms through which tamoxifen exerts its effects against estrogen receptor-positive breast cancer. This study employed single-cell metabolomics based on mass spectrometry to explore the metabolic alterations in breast cancer cells induced by tamoxifen, which is often overlooked in metabolomics studies based on bulk cells. Furthermore, it elucidates the mechanism of tamoxifen’s action against estrogen receptor-positive breast cancer from a single-cell metabolomic perspective, thereby provides valuable insights for understanding the mechanisms underlying other therapeutic agents.

Background and purpose: Human epidermal growth factor receptor 2 (HER2) serves as one of the paramount drivers of breast cancer metastasis, with roughly 20%-30% of breast cancer patients exhibiting high expression of HER2. The expression level of HER2 is regulatable at multiple molecular levels and determines the metastatic potential of breast cancer cells; however, the manner in which HER2 expression is modulated at the mRNA level remains ambiguous. Circ-0007766 is a circRNA originated from the coding gene ERBB2 for HER2, and whether circ-0007766 can regulate HER2 expression via the ceRNA mechanism has not been reported. This study aimed to analyze whether circ-0007766 acts as a miR-1972 sponge to promote breast cancer cell migration and invasion via upregulation of HER2 expression. Methods: In this study, a high-throughput circRNA chip was employed to screen for circRNAs that exhibited highly specific expression in HER2-positive breast cancer cells. RNA fluorescence in situ hybridization (FISH) was utilized to detect the subcellular localization of circ-0007766. The BaseScope experiment was conducted to analyze the expression level of circ-0007766 in breast cancer tissues and its clinical diagnostic significance. Breast cancer cell models with overexpression and knockdown of circ-0007766 were constructed by transfecting cloning plasmids and siRNA in vitro. The effect of circ-0007766 on the migration and invasion of breast cancer cells was assessed using transwell migration and invasion experiments, and the migration and invasion abilities of MDA-MB-231 and SK-BR-3 cells were measured. Additionally, it was evaluated whether circ-0007766 could promote the migration and invasion of breast cancer cells through miR-1972. A dual luciferase reporter gene assay was used to verify whether circ-0007766 could regulate HER2 expression by binding to miR-1972. The direct interaction between circ-0007766 and miR-1972 was further verified through the RAP experiment. RIP detection was performed in MDA-MB-231 cells, and the relative 3'UTR of HER2 mRNA was measured by real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR). Western blot was used to detect the protein expressions. Results: Circ-0007766 was conspicuously highly expressed in HER2-positive breast cancer cells and distributed in both the cytoplasm and nucleus of cells, with the preponderance being in the cytoplasm. The expression level of circ-0007766 was strikingly higher in breast cancer tissues than in para-cancerous tissues. The expression of circ-0007766 was significantly elevated in HER2-positive breast cancer samples compared with HER2-negative samples. The overexpression (knockdown) of circ-0007766 in HER2-negative breast cancer cells (in HER2-positive breast cancer cells) was capable of promoting (inhibiting) the migration and invasion of breast cancer cells. Circ-0007766 directly bound to miR-1972, which inhibited breast cancer cell migration and invasion, thereby forming an endogenous competitive RNA (ceRNA) regulatory network and impeding the downregulation of HER2 mRNA and protein expression mediated by miR-1972. Circ-0007766 could potentiate the inhibitory effect of miR-1972 on HER2-mediated breast cancer cell migration and invasion that was negatively regulated by miR-1972. CircRNAs sequestered miRNAs to function as ceRNAs, thereby regulating gene expression at both the transcriptional and translational levels. Finally, we discovered that the expressions of circ-0007766 and HER2 were positively correlated in breast cancer cell and tissue samples, while the expression levels of miR-1972 and HER2 were negatively correlated. Circ-0007766 could specifically target miR-1972 to hinder its regulatory effect on HER2 expression. Conclusion: This study discovers that circ-0007766 facilitates the migration and invasion of breast cancer cells via the miR-1972/HER2 signal axis, offering a novel biomarker and potential therapeutic target for patients with metastatic HER2-positive breast cancer.

Background and purpose: Breast cancer is a major global public health problem. Bone is the most common site of distant metastasis of breast cancer, accounting for about 70% of all metastatic cases. Bone metastasis of breast cancer can cause a series of complications, including severe pain, pathological fracture, hypercalcemia, spinal cord compression, etc., which bring great inconvenience to patients' physical activities and affect their quality of life. Metastatic recurrence is the leading cause of death in breast cancer patients. Therefore, there is an urgent need to build a diagnostic model of bone metastasis in breast cancer to identify patients with a high risk of bone metastasis. The aim of this study was to develop a predictive model based on machine learning to predict the probability of breast cancer developing bone metastasis. Methods: Data of breast cancer patients diagnosed between 2010 and 2015 were extracted from The Surveillance, Epidemiology, and End Results (SEER) database. The variables were screened by least absolute shrinkage and selection operator (LASSO) regression, univariate and multivariate logistic regression analysis, and statistically significant risk factors were included to build a prediction model. In this study, nine machine learning algorithms, including decision tree, elastic network, K-nearest neighbor, lightweight gradient elevator, logistic regression, neural network, random forest, support vector machine and limit gradient lifting, were used to adjust the model hyperparameters through random search and 5x cross-validation to build a breast cancer bone metastasis prediction model. The area under the receiver operating characteristic (ROC) curve, calibration curve and decision curve were used to evaluate the model, the optimal model was obtained, and the importance of variables was analyzed based on the optimal model. Finally, a network calculator for predicting the risk of bone metastasis of breast cancer was established using the optimal model. Results: The study included 10 106 patients with breast cancer, 7 073 patients in the training set, and 3 033 patients in the validation set. We found that 4 494 (63.5%) patients in the training set and 1 927 (63.5%) patients in the validation set developed bone metastases, respectively. Race, pathologic grade, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth factor receptor 2 (HER2) status, N stage, lung metastasis, radiotherapy, chemotherapy and surgery were independent predictors of bone metastasis. The training set and verification set were used to verify the model, and the limit gradient lifting algorithm was superior to other machine learning algorithms by integrating the evaluation indexes such as the area under the ROC curve, calibration curve and decision curve. Finally, we used limit gradient algorithm to build network calculator for prediction of breast cancer bone metastases (https://bcbm.shinyapps.io/DynNomapp/). Conclusion: This study developed a predictive model based on machine learning to predict the probability of bone metastases in breast cancer patients, hoping to help clinicians make more rational treatment decisions.

Endocrine therapy is the most important adjuvant treatment for early estrogen receptor (ER)-positive breast cancer. ER-low-positive (immunohistochemistry staining 1%-10%) breast cancer has drawn widespread attention in recent years. This group accounts for 3%-9% of overall breast cancer patients. The efficacy of endocrine adjuvant therapy is relatively limited in patients with ER-low-positive breast cancer. Although the proportion of patients with low ER expression in breast cancer population is relatively low, the clinical needs of this population can not be ignored because of the large number of breast cancer patients. A number of studies have suggested that ER-low-positive breast cancer is different from ER-positive breast cancer, and is similar to ER-negative breast cancer in terms of molecular and biological characteristics, clinical features and prognosis. There are still controversies on the benefit and duration of endocrine therapy for early ER-low-positive breast cancer, and there is a lack of evidence from large-scale prospective studies. Multiple retrospective studies and meta-analyses have suggested that ER-low-positive breast cancer may have limited benefit from adjuvant endocrine therapy, and therefore endocrine therapy should be considered with caution in this population. The benefit of adjuvant therapy combined with cyclin-dependent kinase (CDK) 4/6 inhibitors is yet to be supported by future data. Some patients with ER-low-positive breast cancer may try adjuvant chemotherapy in consideration of other risk factors. Additionally, clinical trials that test antibody-drug conjugates (such as sacituzumab govitecan and Dato-DXd), poly (ADP-ribose) polymerase (PARP) inhibitors, and immunotherapies for the treatment of early ER-low-positive breast cancer are still ongoing, including the phase Ⅲ ASCENT-05 study evaluating the adjuvant therapy of sacituzumab govitecan combined with pembrolizumab in high-risk human epidermal growth factor receptor 2 (HER2)-negative, ER and progesterone receptor (PR)

Background and purpose: Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA special binding protein that participates in regulating the expression of related genes and protein translation. It has been linked to the malignant occurrence and development of various tumors, but its role in breast cancer remains unclear. The aim of this study was to investigate the effects of hnRNPK on ferroptosis in breast cancer cells and the underlying mechanisms. Methods: Based on The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, hnRNPK expression in breast cancer tissues and normal tissues and its relationship with clinical prognosis were analyzed by bioinformatics. We detected hnRNPK expression in breast cancer cells and tissues using real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), Western blot, and immunohistochemistry staining diagnosis methods. MCF-7 and MDA-MB-231 breast cancer cells were transfected with siRNA, and divided into control group (control), empty body group (NC), and interference vector group (si-hnRNPK). Cell proliferation was detected by cell counting kit-8 (CCK-8) and plate clone formation assays. RNA-seq analysis was applied to explore potential targeted biological functions and signaling pathways affected by hnRNPK. Additionally, we investigated the impact of hnRNPK on ferroptosis phenotype using Western blot and commercial kits for reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and Fe2+, ferroptosis inhibitor (ferrostatin-1, Fer-1) was used to detect the rescue effect of hnRNPK knockdown on ferroptosis. The impact of hnRNPK on the expressions of Wnt/β-catenin pathway-related proteins were determined by Western blot. Results: The bioinformatics analyses indicated hnRNPK was upregulated in breast cancer tissues (P

Vasculogenic mimicry (VM) is a blood vessel-like structure formed by tumor cells and extracellular matrix, which can mimic the function of blood vessels while providing nutrients to tumors. Tumor angiogenesis plays an important role in tumor cell growth, invasion and metastasis. Anti-angiogenic drugs have been applied in breast cancer treatment, but the drug effects are still limited and susceptible to drug resistance. The formation of VM is one of the reasons leading to resistance to anti-angiogenic drugs. In addition, although the mechanism of VM formation has not been completely clarified, it is associated with a variety of poor prognostic factors in breast cancer, such as more aggressive staging, larger tumor diameter, and more prone to lymph node metastasis. Early intervention in the formation of VM may improve the prognosis of breast cancer, and therefore, targeting the VM may become a major new direction in the treatment of breast cancer. This article focuses on the molecular mechanisms of VM formation, the drivers of associated VM in breast cancer, the clinical relevance of VM in breast cancer, and the treatment targeting at VM.

Breast cancer is one of the most common malignancies in women, and its incidence rate keeps ahead of all malignancies. At present, ultrasound and pathological examination are main methods for diagnosing breast cancer. The development and progression of breast cancer are a complex process involving multiple immunohistochemical indicators. Different immunohistochemical expression of breast cancer causes different pathological changes, resulting in a series of ultrasound imaging changes. More and more studies have found that ultrasound signs of breast cancer are associated with immunohistochemical indicators. Herein, the research progress on ultrasound signs of breast cancer and their relationship with the expression of immunohistochemical indicators is summarized through literature review to provide a reference for developing treatment plans and predicting the prognosis of breast cancer.

"Objective To analyze multimodal ultrasonic characteristics of human epidermal growth factor receptor 2 (HER-2) positive breast cancer patients in different hormone receptor (HR) expression states, so as to provide a reference for the early diagnosis and treatment of HER-2 positive breast cancer. Methods The clinical data of 160 patients with HER-2 positive breast cancer who were diagnosed and treated in the First Affiliated Hospital with Nanjing Medical University and Jurong Peoples Hospital from January 2017 to December 2023 were collected retrospectively. According to immunohistochemical results, patients were divided into HR positive group (n=89) and HR negative group (n=71). General data, pathological characteristics and multimodal ultrasonic characteristics of the two groups were compared. Logistic regression analysis was performed to analyze the relationship between multimodal ultrasonic characteristics and HR expression in HER-2 positive breast cancer. The receiver operating characteristic (ROC) curve was used to analyze the predictive value of multimodal ultrasonic characteristics for HR expression in HER-2 positive breast cancer patients. Results Compared with HR negative group, proportions of routine ultrasound signs (irregular shape, edge anomaly or fuzziness, microcalcification, internal uneven echo) significantly decreased in HR positive group, and proportions of contrast-enhanced ultrasound signs (irregular shape, fuzzy boundary and non-filling defect after enhancement) significantly decreased (P＜0.05). Compared with HR negative group, difference value of lesion diameter in contrast-enhanced ultrasound sign ［(3.29±0.36) mm vs (4.30±0.44) mm, t=15.971, P＜0.01］, elasticity score ［(3.15±0.33) points vs (4.56±0.47) points, t=21.416, P＜0.01］ and hardness ratio ［(0.24±0.04) points vs (0.33±0.05) points, t=12.340, P＜0.01］ in elastography signs significantly decreased in HR positive group. Logistic regression analysis showed that difference value of lesion diameter, elasticity score and hardness ratio after enhancement were closely related to HR expression (P＜0.05). ROC curve analysis showed that the area under the curve of three characteristics of ultrasoud multimodality combined to predict the HR expression status in patients with HER-2 positive breast cancer (0.895) was larger than that of the lesion diameter difference (0.641), elasticity score (0.833) and hardness ratio (0.783) (Z=7.524, 3.405, 4.420, P＜0.05), and the specificity and Youden index of combined prediction were also the highest. Conclusion HR positive expression in patients with HER-2 positive breast cancer is closely related to multimodal ultrasonic characteristics. Multimodal ultrasonic characteristics have a high predictive value for HR positive expression in HER-2 positive patients."

"Objective To detect the expression of vascular endothelial growth factor (VEGF) and microvessel density in cancer tissues of breast cancer patients, and to analyze their relationship with clinicopathological characteristics of breast cancer. Methods Ninety-six breast cancer patients treated at the Fourth Affiliated Hospital of Nanjing Medical University from December 2021 to December 2022 were selected as the research subjects. According to whether the pathology was confirmed as triple-negative breast cancer (TNBC), they were divided into the TNBC group (24 cases) and the non-TNBC group (72 cases). Immunohistochemistry was used to detect the expression of VEGF protein in breast cancer tissues, and microvessel density was evaluated by immunohistochemical labeling of endothelial cells followed by counting the number of microvessels. The relationship between the two and the clinicopathological characteristics of breast cancer was analyzed. Results The positive rate of VEGF in TNBC patients(66.67%) was higher than that in non-TNBC patients (25.00%), with a significant difference (χ2=13.662, P＜0.01); the microvessel density in TNBC patients（66.04±10.29) was higher than that in non-TNBC patients (61.07±10.36), with a significant difference (t=2.039, P=0.044). In the TNBC group, the positive expression rate of VEGF in patients with clinical stage Ⅰ-Ⅱ and no lymph node metastasis was significantly lower than that in patients with clinical stage Ⅲ and lymph node metastasis (P＜0.05), and the microvascular density in patients with tumor diameter≥2 cm and clinical stage Ⅲ was significantly higher than that in patients with tumor diameter＜2 cm and clinical stage Ⅰ-Ⅱ (P＜0.05). In non-TNBC group, there was no significant difference in VEGF positive expression rate and microvessel density between patients with different clinicopathological characteristics (P＞0.05). Conclusion In TNBC patients, the high expression of VEGF and the increase of microvessel density are related to the tumor diameter, clinical stage and lymph node metastasis of TNBC, which is helpful to predict the prognosis of patients and provide a new way to target VEGF pathway or microvessel therapy."

Neutrophils originate from the bone marrow, differentiating from hematopoietic stem cells, and are the most prevalent polymorphonuclear leukocytes in the blood, accounting for approximately 70% of the total white blood cells in adult peripheral blood. Neutrophils are recognized as one of the relatively short-lived cells in the body, with a normal half-life of just a few hours in the peripheral blood, which rely on continuous replenishment from the bone marrow to maintain the number. As short-lived effectors of the innate immune system, neutrophils participate in various inflammatory and immune processes, and constitute the first line of defense against infection, playing a crucial role in the activation and regulation of both innate and adaptive immunity. Neutrophils were once considered as key effectors of inflammation and infection. Because of their short lifespan and non-proliferative nature, the role of neutrophils in cancer was overlooked. Their role in cancer has been increasingly recognized in recent years. However, more and more studies demonstrate that neutrophils play a much more significant role in cancer than previously thought. Breast cancer is one of the common malignant tumors in women, and its morbidity and mortality are in the forefront of female malignant tumors. The incidence of breast cancer is rising globally, posing a severe threat to the physical and mental health of women worldwide. Recent studies confirm that tumor-associated neutrophils (TANs) have become a critical component of the tumor microenvironment (TME) and play a significant role in the development, progression and metastasis of breast cancer. TANs are formed via the interaction of various tumor-derived cytokines which stimulate and recruit neutrophils to accumulate in the TME. The strong plasticity and diversity of neutrophils endow TANs with dual potential to both promote and inhibit tumors. TANs advance breast cancer progression by promoting tumor growth and metastasis, supporting tumor angiogenesis, immune suppression, and generating neutrophil extracellular traps (NETs). Conversely, TANs mediate antitumor responses through direct tumor cell killing and contributing to the formation of antitumor immune network. Research on TANs-related breast cancer therapies, particularly in triple-negative breast cancer (TNBC), has become a research hotspot. This review summarized recent advances in the origin, formation, classification and function of TANs in breast cancer, as well as a detailed discussion of their clinical relevance. We further combined recent clinical studies to systematically summarize the treatment strategies targeting TANs in breast cancer, with the aim of providing new insights into the functional mechanisms of TANs and the treatment of breast cancer.

Objective To analyze the impact of endoscopy surgery and open surgery on the quality of life of breast cancer patients. Methods Three hundred and forty-four female breast cancer patients who underwent two different surgical methods were collected， including 92 cases in the endoscopic surgery group and 252 cases in the open surgery group. Functional Assessment of Cancer Therapy-Breast （FACT-B） was used to investigate the quality of life of patients after surgery in two groups. Results The FACT-B items“I am satisfied with my sex life”“I am able to work （including home work）”“My work （including home work） makes me feel a sense of accomplishment”“I feel sexually attractive”“I still feel like a woman”“I worry about the effect of stress on my disease”were statistically significant in two groups （all P < 0.05），the endoscopic surgery group was superior to the open surgery group. There was no significant difference in the other items between the two groups （all P > 0.05）. Conclusion The quality of life of breast cancer patients undergoing endoscopy surgery was better than that of patients undergoing open surgery.

Objective·To develop a machine learning approach for early identification of metabolic syndromes associated with inflammatory metabolic state changes in breast cancer patients after neoadjuvant therapy, using common laboratory and transthoracic echocardiography indices.Methods·Female patients with primary invasive breast cancer diagnosed at the Department of Breast Surgery, Renji Hospital, Shanghai Jiao Tong University School of Medicine, between September 2020 and September 2022, were included. General patient information, laboratory test results, and transthoracic echocardiography data were collected. After feature extraction, five machine learning algorithms, including random forest (RF), gradient boosting (GB), support vector machine (SVM), K-nearest neighbor (KNN), and decision tree (DT), were applied to construct a prediction model for the changes of the patients′ metabolic state after neoadjuvant therapy, and the prediction performances of the five models were compared.Results·A total of 232 cases with valid clinical data were included, comprising 135 cases before neoadjuvant therapy and 97 cases after completing 4 cycles of neoadjuvant therapy. Feature extraction identified five key features: white blood cell count, hemoglobin, high-density lipoprotein (HDL), interleukin-2 receptor, and interleukin-8. In the multi-feature analysis, the area under the receiver operating characferistic curve (AUC) was higher in the combination of white blood cell count, hemoglobin and HDL compared to the combination of interleukin-2 receptor and interleukin-8 (RF: 0.928 vs 0.772, GB: 0.900 vs 0.792, SVM: 0.941 vs 0.764, KNN: 0.907 vs 0.762, DT: 0.799 vs 0.714). The RF, SVM, and GB models showed higher AUC (0.928, 0.941, 0.900) and accuracy (0.914, 0.897, 0.776). The SVM model exhibited superior accuracy in the training data compared to the RF and GB models (P=0.394, 0.122 and 0.097, respectively).Conclusion·The SVM model can be used to establish a prediction model for identifying breast cancer patients at high risk of developing inflammatory metabolic state-related metabolic syndrome after neoadjuvant therapy by incorporating five common clinical indicators, namely, white blood cell count, hemoglobin, high-density lipoprotein, interleukin-2 receptor, and interleukin-8. SVM modeling may be useful for clinicians to establish individualized screening protocols based on a patient′s inflammatory metabolic state.

ObjectiveTo compare the efficacy of trastuzumab plus pertuzumab (HP) combined with either nab-paclitaxel plus carboplatin or docetaxel plus carboplatin as neoadjuvant therapy for HER2-positive breast cancer in real-world clinical practice. MethodsClinical data of HER2-positive breast cancer patients who received neoadjuvant therapy with either HP combined with nab-paclitaxel plus carboplatin or HP combined with docetaxel plus carboplatin and subsequently underwent surgery were retrospectively collected from 11 tertiary grade-A hospitals in Hebei Province from June 2019 to December 2021. The total pathological complete response (tpCR) rates of the two groups were compared. ResultsA total of 76 patients were included in the study, with 47 in the nab-paclitaxel group and 29 in the docetaxel group. The tpCR rate was significantly higher in the nab-paclitaxel group than that in the docetaxel group (72.3% vs. 48.3%, χ2=4.463, P=0.035). Subgroup analysis indicated that patients older than 40 years, with cN2-3, cTNM stage Ⅲ, hormone receptor-positive status, and Ki67>30% had significantly higher tpCR rates in the nab-paclitaxel group than those in the docetaxel group (P

Objective To establish breast cancer organoids for a long time and to characterize their molecular expression and test their sensitivity to chemotherapy drugs. Methods Breast cancer specimens were digested with collagenase to release cancer cells for organoid culture. The organoids were characterized by morphology and ER,PR,HER-2,CK expression by technology of histoimmunofluorescence. Among them, three were tested for paclitaxel, doxorubicin and cisplatin sensitivity. Results A total of 44 cases of breast cancer organoids were established, all of which showed dense spherical-like growth and ER,PR,HER-2,CK, matching their clinical counterpart. Breast cancer organoids were sensitive to chemotherapy drugs paclitaxel, doxorubicin and cisplatin. Conclusions Organoid model, as a new in vitro may reproduce the pathophysiology features with heterogeneity.

Breast cancer is one of the most common cancers of females and is a leading cause of tumor-related death in women. Negative emotion frequently presents in patients like anxiety and depression and chronic stress which may lead to depression is a major risk factor of the cancer development. Stress leads to dysfunctions of cells, molecules and neural circuits, thus promoting depression. Chronic stress promotes the occurrence and development of breast cancer through related neurotransmitters and also affects the prognosis of breast cancer patients.

BackgroundCompliance of functional exercise has considerable impact on the effectiveness of postoperative rehabilitation among patients with breast cancer. Both symptom burden and hope level of patients are in relation with the compliance mentioned above， but there is limited evidence for the relationship among the three in patients after breast cancer surgery.ObjectiveTo explore the pathway of hope level between symptom burden and functional exercise compliance in patients after breast cancer surgery， with intention to provide references for improving their functional exercise compliance.MethodsFrom March 26 to December 9， 2023， 312 patients who received breast cancer surgery in a tertiary grade A hospital in Sichuan Province were selected as the study objects. Investigation was conducted by adopting scales including the Chinese version of the M. D. Anderson Symptom Inventory （MDASI-C）， the Chinese version of the Herth Hope Scale （HHS-C） and the Functional Exercise Compliance Scale among breast cancer patients after discharge. Pearson correlation analysis was used to examine the correlation among each scale score. Model 4 from the macro program Process of SPSS 25.0 was used to analyze the pathway of hope level between symptom burden and functional exercise compliance.ResultsA total of 308 patients （98.72%） after breast cancer surgery completed effective questionnaire survey. As results showed， MDASI-C score was negatively correlated with scores of HHS-C and functional exercise compliance （r=-0.202， -0.279， P

Objective To establish an animal model and evaluation system for lymph node metastasis of breast cancer. Methods A total of 60 female BALB/c mice (6~8 weeks old) were subjected, and then 6 models of lymph node metastasis (n=10) were constructed through injection at different parts in the mice with cell suspension of 4T1 breast cancer cells.Transgenic mice (n=5) of mouse mammary tumor virus-polyoma middle T antigen (MMTV-PyMT) were employed and served as model of spontaneous tumor metastasis.Then the advantages and disadvantages of different lymph node metastasis models were comprehensively evaluated from multiple aspects, such as operability, histomorphology and pathological detection, tumor growth rate and mouse survival. Results Among the 7 metastasis models, 4 models of lymph node metastasis were successfully established.Among them, the PyMT mouse spontaneous tumorigenesis model showed the best clinical reproduction, with a tumorigenesis rate of up to 100%, but had a disadvantage of poor experimental standardization.The hind paw-popliteal lymph node model had the fastest lymph node metastasis, easy operation and high repeatability, and a tumorigenesis rate of 100%, indicating its suitable for lymph node metastasis related research.The thigh subcutaneous-inguinal lymph node model also successfully simulated lymph node metastasis, with simple operation and high repeatability, a tumorigenesis rate of up to 100%, but its metastasis time was slightly longer than the hind paw-popliteal lymph node model.The inguinal lymph node-contralateral lymph node model was also a successful lymph node metastasis model, but with difficult operation, only 50% tumor-bearing rate, and poor repeatability.Lymph node metastasis model was not successfully established in the other 3 tumor-bearing models (under the tongue-internal jugular scapular tongue muscle lymph node model, bone marrow-inguinal lymph node model and right upper back skin-axillary lymph node model) in a short time, with no tumor cells observed in the pathological sections. Conclusion Through the comprehensive comparison of multiple models, mouse hind paw-popliteal lymph node model is the most suitable for conducting related research.

Objective·To examine the expression level of protein arginine methyltransferase 6 (PRMT6) in breast carcinoma tissues and to assess its impact on the proliferative and migratory behaviors of breast cancer cells.Methods·The PRMT6 transcriptome sequencing data between 33 tumor tissues and normal tissues from The Cancer Genome Atlas (TCGA) database was analyzed through the R language. The gene expression profile interactive analysis (GEPIA2) online database was used to analyze the difference of PRMT6 expression in normal breast tissues and breast cancer tissues. By using the immunohistochemistry (IHC) data of human normal breast tissues and breast cancer tissues from Human Protein Atlas (HPA) database to analyze the protein expression of PRMT6. IHC was used to detect the expression of PRMT6 in breast cancer tissues and paired para-tumor tissues from 27 clinical samples. After PRMT6 was knocked down with small interfering RNA (siRNA) in MDA-MB-231 and MCF-7 cells , the expression of PRMT6 was detected by qRT-PCR and Western blotting. The proliferation ability of breast cancer cells was measured with cell counting kit-8 (CCK-8) assay and colony formation assay. The effect of PRMT6 on the migration ability of breast cancer cells was detected by wound healing assay and Transwell assay. By using the RNA-sequence data from GSE210948 of Gene Expression Omnibus (GEO) database, differentially expressed genes were analyzed in control and low expression groups of PRMT6. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to reveal the signaling pathways associated with PRMT6. Cell cycle analysis was detected by flow cytometry. The expressions of cyclin D1 and EMT-related proteins (E-cadherin, N-cadherin and Vimentin) were detected by Western blotting after knocking down PRMT6.Results·Bioinformatics analysis and IHC results showed that PRMT6 was highly expressed in breast cancer tissues compared with normal tissues (P=0.000) and para-tumor tissues (P=0.001). qRT-PCR and Western blotting results verified that the siRNA significantly reduced the expression level of PRMT6 in MDA-MB-231 and MCF-7 cell lines compared with the control group (mRNA: P=0.006, P=0.004; P=0.001, P=0.043. Protein: P=0.035, P=0.001; P=0.003, P=0.002). After knocking down PRMT6, the proliferation (P=0.014, P=0.000; P=0.003, P=0.003) and migration (P=0.000, P=0.000; P=0.000, P=0.002) ability of breast cancer cells were inhibited significantly . The KEGG pathway enrichment analysis showed that the expression of PRMT6 affected the cell cycle pathway. After knocking down PRMT6, the expression of cyclin D1 decreased in protein level (P=0.021, P=0.000; P=0.034, P=0.014) and transcription level (P=0.036, P=0.001; P=0.044, P=0.000). Knock down of PRMT6 increased the number of cells in G0/G1 phase (P=0.000; P=0.003) and decreased the number of cells in G2/M phase of the cell cycle . The expression level of E-cadherin increased (P=0.002, P=0.012; P=0.043, P=0.003), while the expression levels of N-cadherin (P=0.004, P=0.041; P=0.032, P=0.034) and Vimentin (P=0.028, P=0.005; P=0.024, P=0.001) decreased in PRMT6 knockdown cells .Conclusion·PRMT6 is highly expressed in breast cancer, which can promote the proliferation and migration of breast cancer cells.

ObjectiveTo analyze the experience of Professor Chen Huanchao, a famous TCM doctor in Hubei Province, in treating breast cancer by data mining technology. MethodsThe medical records of Professor Chen Huanchao’s treatment of breast cancer were collected, and the first prescription of each patient was recorded after screening and sorting. MS Excel 2019 was used to analyze drug frequency, efficacy frequency, and the meridian distribution, and SPSS Modeler 18.0 software was adopted for association rule analysis and network display of drugs. SPSS 27.0 was employed for clustering analysis of high-frequency drugs to summarize medication patterns. ResultsA total of 185 prescriptions involving 180 traditional Chinese medicines were included, and 29 high-frequency drugs were screened. The medicinal properties were mainly neutral, cold, and warm, and the medicinal flavors were mainly sweet, bitter, and pungent. The meridians were liver, lung, spleen, and kidney meridians. The medicinal effects primarily included tonifying deficiency, clearing heat, and promoting diuresis and dampness. The association rule analysis showed 20 groups of drug pairs, and the cluster analysis mainly revealed two categories. ConclusionProfessor Chen Huanchao believes that breast cancer involves root deficiency and excessive symptoms and should be treated from the perspective of “deficiency, blood stasis, phlegm, and toxin.” Genuine-Qi should be strengthened, and Evil-Qi should be eliminated. The symptoms and root causes of this disease should be treated simultaneously while soothing the liver and qi, tonifying the spleen and kidney, promoting blood circulation, removing phlegm and preventing its accumulation, and clearing heat and detoxify. This work provides ideas for the treatment of breast cancer with traditional Chinese medicine.

ObjectiveTo analyze the trends in breast cancer incidence and mortality from 1990 to 2019 and to predict the age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) of breast cancer from 2020 to 2029 in the world female population, providing a reference for the prevention and control of female breast cancer in the world. MethodsData on breast cancer incidence and mortality in the global female population from 1990 to 2019 were collected from the Global Burden of Disease (GBD) 2019 study. Incidence count, incidence rate, ASIR, death count, mortality rate, and ASMR were used for descriptive analysis. Average annual percentage change (AAPC) was used to analyze trends in breast cancer incidence and mortality from 1990 to 2019. The age-period-cohort (APC) model was used to estimate the age effect, period effect, and cohort effect on breast cancer incidence and mortality risk in the world female population; the autoregressive integrated moving average (ARIMA) model was used to predict trends in breast cancer incidence and mortality from 2020 to 2029 in the female population. ResultsIncreases in breast cancer in the global female population from 1990 to 2019 were observed in incidence number (867 620.84 to 1 977 211.62), incidence rate (32.67/100 000 to 51.27/100 000), ASIR (40.12/100 000 to 45. 86/100 000), number of deaths (375 016.06 to 688 562.26), and mortality rate (14.12/100 000 to 17.85/100 000), with total percentage changes of 127.89%, 56.93%, 14.31%, 83.61%, and 26.42%, respectively. The breast cancer ASMR decreased from 17.76/100 000 in 1990 to 15.88/100 000 in 2019, with an overall percentage change of – 10.54%. Joinpoint regression analysis showed that breast cancer ASIR for the global female population generally increased from 1990 to 2019 (AAPC = 0.44, P < 0.001), while breast cancer ASMR generally decreased (AAPC = – 0.37, P < 0.001). Trends in female breast cancer incidence and mortality varied across global regions with different levels of socio-demographic index (SDI) from 1990 to 2019. The ASIR generally increased in global regions with different SDI levels. The ASMR generally increased in the middle, low-middle, and low SDI regions, but generally decreased in the high and high-middle SDI regions from 1990 to 2019 (all P < 0.001). The APC model analysis showed that the age effects on breast cancer incidence and mortality rates in the global female population generally increased with age, with coefficients increasing from – 2.878 and – 2.946 at ages 20 – 24 years to 0.706 and 1.053 at ages 75 – 79 years, respectively. Period effects on breast cancer incidence and mortality also showed increasing trends, with coefficients increasing from – 0.310 and – 0.206 in 1990 – 1994 to 0.296 and 0.235 in 2015 – 2019, respectively. However, cohort effects on breast cancer incidence and mortality generally decreased, with coefficients decreasing from 0.848 and 0.866 for the 1915 – 1919 birth cohort to – 0.575 and – 0.672 for the 1995 – 1999 birth cohort, respectively. ARIMA model predictions showed that the global female breast cancer ASIR will continue to increase while the ASMR will continue to decrease from 2020 to 2029, with predicted ASIR and ASMR of 47.86/100 000 and 15.31/100 000, respectively, in 2029. ConclusionFrom 1990 to 2019, the ASIR for breast cancer has generally increased while the ASMR has generally decreased in the global female population. From 2020 to 2029, the ASIR is projected to continue to increase while the ASMR is projected to continue to decrease.

ObjectiveTo understand the incidence and death of female breast cancer patients and the premature death caused by breast cancer in Putuo District of Shanghai, and to reduce the incidence of breast cancer, mortality and the probability of early death, and to provide reference for realizing the control target of the probability of early death of major chronic diseases.MethodsThe incidence and death data of the registered female residents with breast cancer in Putuo District of Shanghai from 2004 to 2019 were collected using Shanghai Population-based tumor registration management system. The crude incidence rate, standardized incidence rate, crude mortality rate, standardized mortality rate, age-specific incidence rate, age-specific mortality rate and other indicators were calculated. The Joinpoint regression model was used to calculate the annual percentage change (APC) and average annual percentage change (AAPC) of breast cancer incidence, mortality and premature death probability, and to analyze the changing trend.ResultsFrom 2004 to 2019, the crude incidence of breast cancer in Putuo District of Shanghai increased from 75.76/105 to 95.77/105 (APC=2.26%, t=6.05, P

Endocrine therapy plays a crucial role in hormone receptor-positive breast cancer and is closely related to the patient’s menopausal status. This manuscript aimed to explore two key questions in assessing menopausal status of breast cancer patients. Firstly, for premenopausal patients receiving ovarian function suppression (OFS) therapy, persistently elevated estradiol (E2) levels post-treatment may be attributed to either “true” or “pseudo” elevation, with caution needed due to potential interference from endocrine therapy drugs such as fulvestrant, abemaciclib, exemestane and tamoxifen. Secondly, when determining whether patients under OFS therapy have reached physiological menopause, factors such as the impact of chemotherapy on menopausal status and the complexity of hormone levels around menopause need to be considered. It is recommended to consider switching treatments based on the patient’s age and original endocrine therapy, and to regularly monitor levels of estradiol and follicle-stimulating hormone (FSH). In challenging cases, a comprehensive evaluation can be conducted by incorporating markers such as anti-Mullerian hormone (AMH), inhibin B (INHB) and androgen.

Background and purpose: The overexpression of carnitine palmitoyl transferase 1A (CPT1A) is related to the poor prognosis of breast cancer, and it can promote the utilization of fatty acids by mitochondria and maximize triphosphate (ATP) production. However, the role of CPT1A in breast cancer metastasis is still unclear. This study aimed to explore the mechanism that mitochondrial dysfunction and CPT1A/extracellular signal-regulated kinase (ERK) signaling pathway in breast cancer jointly regulate the malignant behavior of breast cancer. Methods: The lentivirus system and shRNA tools were used to overexpress or knock down CPT1A in human breast cancer cell lines MDA-MB-231 and MCF7, and the cells were divided into NC group, CPT1A group and shCPT1A group. The invasion ability of cells was detected by transwell assay, and the protein expressions of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), ERK1/2 and CPT1A were analyzed by Western blot. The mitochondrial morphology of MDA-MB-231 and MCF7 cell lines was analyzed using mitochondrial red staining, and mitochondrial respiratory capacity was analyzed by oxygen consumption rate. Results: Compared with cells expressing control vector, overexpression of CPT1A resulted in enhanced invasion abilities of MCF7 cells and MDA-MB-231 cells (P

Objective To study the effect of Salidroside(Sal) on platelet activation and aggregation and the interaction between human platelets and MDA-MB-468 cells of breast cancer. Methods Human platelets were collected, platelet suspension was prepared, and platelets were treated with different concentrations of Sal. The effects of Sal on platelet activation and aggregation were detected by thromboelastogram(TEG) and flow cytometry. Breast cancer MDA-MB-468 cells were cultured in vitro, and human platelets were treated with different concentrations of Sal, and then activated by thrombin. The effects of Sal on the interaction between platelets and MDA-MB-468 cells were analyzed by adhesion test and scratch test. Results TEG detection: The ADP inhibition rate in the blank control group was (10.97±12.69)%, and the ADP inhibition rate in all Sal intervention groups was higher than that in the blank control group (P

Phosphatase and tensin-homolog deleted on chromosome 10 (PTEN) is an important cancer suppressor gene. Its pathogenic mutation leads to PTEN hamartoma tumor syndrome (PHTS), a rare syndrome also known as Cowden syndrome, which is relevant to early-onset hereditary breast cancer (BC). In this paper, we report three patients with unilateral multicentric BC and synchronous and metachronous bilateral BC who harbored PTEN gene mutations, and summarize the clinical manifestations, pathological characteristics, diagnosis, treatment and follow-up outcomes to provide reference for management of PTEN gene mutation-related BC among the Cowden syndrome population.

Objective To investigate the regulatory mechanism of long non-coding RNA (lncRNA) ENST00000579933 (hereinafter referred to as lncRNA ENST 933) on the development of breast cancer (BC). Methods The expression level of lncRNA ENST 933 in BC tissues as well as in BC cell lines (MCF-7, MDA-MB-231, MDA-MB-453) was detected by fluorescence-based real-time quantitative polymerase chain reaction RT-qPCR. The effects of lncRNA ENST 933 and miR-588 on the proliferation, migration, invasion and cell cycle in BC were determined using CCK-8 assay, clone formation assay, EdU, Transwell assay, flow cytometry, Western blotting and in vivo transplantation tumor assay. Finally, dual luciferase reporter gene, RNA immunoprecipitation assay, RT-qPCR, Western blotting and rescue assay were used to evaluate the interactions among lncRNA ENST 933, miR-588, and eukaryotic initiation factor 6 (EIF6). Results The expression of lncRNA ENST 933 was up-regulated in both BC tissues and BC cell lines (P < 0.05). Overexpression of lncRNA ENST 933 could enhance the proliferation, migration and invasion abilities of BC cells and promote the growth of transplanted tumors, while knockdown of lncRNA ENST 933 resulted in inhibited development of BC and arrested cell cycle (P < 0.05). The expression of miR-588 was obviously down-regulated in BC tissues, and its overexpression inhibited cell proliferation, migration and invasion abilities in the BC cells (P < 0.05). Moreover, the results of rescue assay indicated that lncRNA ENST 933 promoted the expression of target gene EIF6 by competitively binding with miR-588. Western blotting revealed that miR-588 decreased the phosphorylation of AKT and mTOR (P < 0.05). Conclusion lncRNA ENST 933 promotes the progression of BC by modulating the miR-588/EIF6 axis.

Currently, breast cancer is a common malignancy in female, and previous guidelines recommended that one of the key biomarkers for breast cancer, human epidermal growth factor receptor 2 (HER2), is classified as either positive or negative to guide clinicians’ treatment decisions. While nearly half of breast cancer patients have low HER2 expression (IHC expression is 1+ or 2+ and ISH detection is negative), such patients are insensitive to traditional anti-HER2 targeted therapy. However, novel antibody-drug conjugates (ADCs) provide new targeted therapy options for breast cancer patients with low HER2 expression, challenging the traditional binary concept and arousing research enthusiasm. In the latest ASCO/CAP guidelines for HER2 detection in breast cancer, HER2-low breast cancer has been included as a clinical treatment subgroup. This article will review the definition of HER2-low breast cancer, the progress of drug therapy such as ADC, and the current challenges faced by this subgroup.

ObjectiveTo investigate the potential significance of FOXP3 expression in BRCA1/2-mutant breast cancer. MethodsA total of 48 BRCA mutation carriers (16 with BRCA1 and 32 with BRCA2) and 78 age-matched non-carriers were included in this study. Immunohistochemistry was used to detect the expression of FOXP3 in breast cancer tissues. The FOXP3 RNA expression in 39 BRCA1, 36 BRCA2, and 948 non-carrier breast cancer patients from TCGA-BRCA and the correlation with homologous recombination deficiency scores were evaluated to validate the immunohistochemistry results. ResultsThe FOXP3 positive rate was 43.8% (7/16) in BRCA1 mutation carriers, 59.4% (19/32) in BRCA2 mutation carriers, and 9.0% (7/78) in non-carriers. The FOXP3 positive rates in patients with BRCA1/2 mutant breast cancer were significantly higher than those in non-carriers (P=0.002; P

ObjectiveTo explore the causal relationship between Omega-3 fatty acids and the risk of breast cancer via Mendelian randomization analysis. MethodsAnalysis was conducted on data from genome-wide association studies (GWASs) on Omega-3 fatty acids and breast cancer. The selected instrumental variables (IVs) comprised genetic loci associated with Omega-3 fatty acids. Various Mendelian randomization analysis methods, including inverse-variance weighted (IVW) method, MR–Egger regression analysis, weighted median, simple models, and weighted models, were used to evaluate the causal relationship between Omega-3 fatty acids and the risk of breast cancer. ResultsA total of 47 single-nucleotide polymorphisms strongly associated with Omega-3 fatty acids were selected as IVs. The analysis methods, including IVW method, revealed no causal relationship between Omega-3 fatty acids and the risk of breast cancer (P>0.05). Analysis methods, such as MR-Egger regression analysis, did not detect significant gene-level pleiotropy (P=0.319), which indicates the high sensitivity and robustness of analysis results. ConclusionThe findings of this study suggest the absence of a causal relationship between Omega-3 fatty acids and the risk of breast cancer.

ObjectiveTo understand the awareness of breast cancer knowledge and its influencing factors among medical staff in maternal and child health hospitals of all levels in Ordos city. MethodsFrom April to June 2023, a convenient sampling method was used to select 886 medical staff from maternal and child health hospitals at all levels in Ordos city, Inner Mongolia Autonomous Region to conduct a questionnaire survey using Questionnaire Star online platform with a self-designed questionnaire on general demographic information and core knowledge of breast cancer prevention and treatment health education introduced in the national “Breast Cancer Screening Work Plan”, and the willingness to recommend to women to have breast cancer screening at an appropriate age. SPSS 19.0 software was used for multivariate logistic regression model analysis. ResultsA total of 862 valid questionnaires were collected, with an effective response rate of 97.3%. The mean score of the respondents' knowledge of breast cancer prevention and treatment was 15.08 ± 5.88 out of a total score of 24. The results of multivariate analysis showed that the respondents with medical majors (clinical medicine: odds ratio [OR] = 7.50, 95% confidence interval [95%CI]: 2.90 – 19.42; nursing: OR = 4.93, 95%CI: 1.92 – 12.66; other medical majors: OR = 4.70, 95%CI: 1.82 – 12.11), working in ultrasound/imaging departments (OR = 2.01, 95%CI: 1.03 – 3.92), and with a professional title of associate senior or higher (senior physician: OR = 3.54, 95%CI: 1.30 – 9.63; associate senior: OR = 2.56, 95%CI: 1.35 – 4.86) had better awareness of breast cancer prevention and treatment knowledge (all P < 0.05). Among the typical symptoms of breast cancer, the awareness rates of "breast lump" (82.48%), "axillary lymph node enlargement" (74.71%), and "breast skin depression or wrinkling" (74.48%) were higher; among the risk factors for breast cancer, the awareness rates of "long-term use of exogenous estrogen" (64.39%) and "family history of breast or ovarian cancer" (61.14%) were higher; among the common breast cancer screening methods, the awareness rates of clinical breast examination, breast ultrasound, and breast x-ray were all around 90%; the awareness rate of the recommended screening age in the breast cancer screening work plan was 74.71%, but the awareness rate of the screening time interval was only 24.25%. The awareness rates of screening age and screening time interval among breast cancer screening personnel (88.36%, 33.33%) were higher than those of non-breast cancer screening personnel (70.88%, 21.69%) (P < 0.001). Of the respondents, 689 (79.93%) and 684 (79.35%) agreed that breast cancer screening can improve the early detection rate and reduce the mortality rate of breast cancer, respectively, and 831 (96.40%) were willing to recommend regular breast cancer screening to women of appropriate age. ConclusionThe awareness of breast cancer screening and the willingness to recommend breast cancer screening to women of appropriate age among medical staff in maternal and child health hospitals in Ordos city are relatively high, but the awareness of breast cancer prevention and treatment knowledge needs to be improved. Professional training in breast related knowledge should be strengthened for local medical staff.