Search

Breast cancer is the most common malignant tumor in women. Surgery is the main treatment for early breast cancer. At present, great progress has been made in the diagnosis and treatment of early breast cancer. Howover, innovative approaches are still needed to reduce trauma and improve patients' outcomes. With the progress of innovative research on the treatment of breast cancer, non-surgical treatment of breast and axilla has become a research hotspot of treatment of early breast cancer. Microwave ablation, as a minimally invasive and precise local treatment, has the characteristics of speedy ablation, simple operation method, less postoperative complications and so on. At present, microwave ablation has been used to treat early breast cancer, and has achieved clinical efficacy. In addition, some studies have been reported that microwave ablation of early breast cancer is conducive to regulating the tumor immune microenvironment and stimulating the antigen-specific anti-tumor immune effect in the body. This immune effect may be related to the massive release of tumor antigen after microwave ablation. The effect of immunotherapy alone for breast cancer is poor. Some researchers have proposed a scheme to enhance the ablation immune effect through combined immunotherapy, but its specific effect still needs more clinical data support. With more and more research on the immune effect induced by ablation therapy, microwave ablation combined with immune checkpoint inhibitor is expected to become a new strategy in the precise treatment of breast tumor. This article summarized the new progress and future development direction of microwave ablation in local precise treatment of breast cancer.

Currently, the improvement in AI is mainly related to deep learning techniques that are employed for the classification, identification, and quantification of patterns in clinical images. The deep learning models show more remarkable performance than the traditional methods for medical image processing tasks, such as skin cancer, colorectal cancer, brain tumour, cardiac disease, Breast cancer (BrC), and a few more. The manual diagnosis of medical issues always requires an expert and is also expensive. Therefore, developing some computer diagnosis techniques based on deep learning is essential. Breast cancer is the most frequently diagnosed cancer in females with a rapidly growing percentage. It is estimated that patients with BrC will rise to 70% in the next 20 years. If diagnosed at a later stage, the survival rate of patients with BrC is shallow. Hence, early detection is essential, increasing the survival rate to 50%. A new framework for BrC classification is presented that utilises deep learning and feature optimization. The significant steps of the presented framework include (i) hybrid contrast enhancement of acquired images, (ii) data augmentation to facilitate better learning of the Convolutional Neural Network (CNN) model, (iii) a pre‐trained ResNet‐101 model is utilised and modified according to selected dataset classes, (iv) deep transfer learning based model training for feature extraction, (v) the fusion of features using the proposed highly corrected function‐controlled canonical correlation analysis approach, and (vi) optimal feature selection using the modified Satin Bowerbird Optimization controlled Newton Raphson algorithm that finally classified using 10 machine learning classifiers. The experiments of the proposed framework have been carried out using the most critical and publicly available dataset, such as CBIS‐DDSM, and obtained the best accuracy of 94.5% along with improved computation time. The comparison depicts that the presented method surpasses the current state‐of‐the‐art approaches. [ABSTRACT FROM AUTHOR]

Background and Aim: Severe colitis is a common side effect of chemotherapy in cancer patients. In this study, we attempted to enhance the viability of probiotics in a gastric acid environment and improve the colitis induced by dextran sulfate sodium (DSS) and docetaxel. Methods: We purified Lactobacillus from yogurt and estimated their growth at pH 6.8 and pH 2.0. In the further investigation, the bacterial biofilm formation was used to define the mechanism by which administration of Lactobacillus rhamnosus (LGG) via oral gavage alleviates the colitis and intestine permeability of the mice induced by DSS and docetaxel. The potential benefit of probiotics on the treatment of breast cancer metastasis has been assessed as well. Results: Lactobacillus from yogurt growth was unexpectedly faster in the pH 2.0 than in the neutral pH medium during the first hour. LGG administered in the fasting state via oral gavage significantly improved the preventive effect in the colitis caused by DSS and docetaxel. LGG reduced the permeability of the intestine and decreased the expression of proinflammatory cytokines, TNF‐α, IL‐1β, and IL‐6, in colitis by biofilm formation. Increasing the docetaxel dose may reduce breast tumor growth and metastasis in the lung but did not benefit survival due to severe colitis. However, the LGG supplement significantly improved the survival of tumor‐bearing mice following a high dose of docetaxel treatment. Conclusions: Our findings provide new insights into the potential mechanism of probiotic protection of the intestine and provide a novel therapeutic strategy to augment the chemotherapeutic treatment of tumors. [ABSTRACT FROM AUTHOR]

Detection of breast mass plays a very important role in making the diagnosis of breast cancer. For faster detection of breast cancer caused by breast mass, we developed a novel and efficient patch-based breast mass detection system for mammography images. The proposed framework is comprised of three modules, including pre-processing, multiple-level breast tissue segmentation, and final breast mass detection. An improved Deeplabv3+ model for pectoral muscle removal is deployed in pre-processing. We then proposed a multiple-level thresholding segmentation method to segment breast mass and obtained the connected components (ConCs), where the corresponding image patch to each ConC is extracted for mass detection. In the final detection stage, each image patch is classified into breast mass and breast tissue background by trained deep learning models. The patches that are classified as breast mass are then taken as the candidates for breast mass. To reduce the false positive rate in the detection results, we applied the non-maximum suppression algorithm to combine the overlapped detection results. Once an image patch is considered a breast mass, the accurate detection result can then be retrieved from the corresponding ConC in the segmented images. Moreover, a coarse segmentation result can be simultaneously retrieved after detection. Compared to the state-of-the-art methods, the proposed method achieved comparable performance. On CBIS-DDSM, the proposed method achieved a detection sensitivity of 0.87 at 2.86 FPI (False Positive rate per Image), while the sensitivity reached 0.96 on INbreast with an FPI of only 1.29. [ABSTRACT FROM AUTHOR]

Purpose: Solute carrier family 7, member 5 (SLC7A5) is reportedly a key gene in various tumors. However, the relationship between SLC7A5 and immune cell infiltration in breast cancer remains elusive. In this study, we investigated the expression levels and clinical value of SLC7A5 using the R package in breast cancer through the TCGA database. Methods: Public transcript data and clinical information of patients were downloaded from the TCGA database. Prognosis analysis was performed to explore the clinical value of SLC7A5 as well as drug sensitivity prediction and Gene Set Enrichment Analysis (GSEA). We also explored the correlations between SLC7A5 and immune infiltration as well as immune markers. Results: We observed that high SLC7A5 expression levels were related to poor survival. Our GSEA demonstrated that G protein-coupled receptor-ligand binding, interleukin signaling, neutrophil degranulation, amino acid and derivative metabolism, and Rho GTPase signaling were differentially enriched in the SLC7A5 high-expression phenotype. Patients in the low SLC7A5 expression group showed sensitivity to paclitaxel and doxorubicin. Conclusion: SLC7A5 could serve as a biomarker for breast cancer prognosis. [ABSTRACT FROM AUTHOR]

Minimally invasive thermal therapies have been attempted in the treatment of breast cancer, and the immune response induced by these therapies has not been fully reported. A clinical trial is performed to determine the effect of microwave ablation (MWA) in the treatment of early‐stage breast cancer. The authors perform single‐cell RNA sequencing on peripheral blood mononuclear cells (PBMCs) from six patients before and after ablation. NK and CD8+T cells are activated by MWA of breast cancer, with the increased inhibitory signature of CD8+T cells but not dysfunctional. Enhanced co‐stimulatory signature of CD4+ T cells is observed and increased frequency of ICOS+CD4+ T cells after MWA is confirmed by flow cytometric analysis. After ablation, T‐cell clones expand with increased T‐cell receptor diversities. Activated antigen receptor‐mediated signaling pathways are found in B cells. Enhanced interactions between B cells and CD4+ T cells are found, indicating that B cells are important antigen‐presenting cells that initiate CD4+T cells in MWA‐induced immune response. Blockade of CTLA‐4 or PD‐1 of post‐MWA PBMCs show higher T‐cell activity than that of pre‐MWA PBMCs. This study provide global characteristics of MWA‐induced systemic immune response and pave a way for the identification of potential targets to improve the immune response. [ABSTRACT FROM AUTHOR]

The visual inspection of histopathological samples is the benchmark for detecting breast cancer, but a strenuous and complicated process takes a long time of the pathologist practice. Deep learning models have shown excellent outcomes in clinical diagnosis and image processing and advances in various fields, including drug development, frequency simulation, and optimization techniques. However, the resemblance of histopathologic images of breast cancer and the inclusion of stable and infected tissues in different areas make detecting and classifying tumors on entire slide images more difficult. In breast cancer, a correct diagnosis is needed for complete care in a limited amount of time. An effective detection can relieve the pathologist's workload and mitigate diagnostic subjectivity. Therefore, this research work investigates improved the pre‐trained xception and deeplabv3+ design semantic model. The model has been trained on input images with ground masks on the tuned parameters that significantly improve the segmentation of ultrasound breast images into respective classes, that is, benign/malignant. The segmentation model delivered an accuracy of greater than 99% to prove the model's effectiveness. The segmented images and histopathological breast images are transferred to the 4‐qubit‐quantum circuit with six‐layered architecture to detect breast malignancy. The proposed framework achieved remarkable performance as contrasted to currently published methodologies. Highlights: This research proposed hybrid semantic model using pre‐trained xception and deeplabv3 for breast microscopic cancer classification in to benign and malignant classes at accuracy of 95% accuracy, 99% accuracy for detection of breast malignancy. [ABSTRACT FROM AUTHOR]

Introduction: Negative margins in breast-conserving surgery (BCS) are essential for preventing recurrence. The aim of this study was to determine the use of preoperative microwave ablation (MWA) in the guidance of BCS for early-stage breast cancer and access whether MWA could influence the rates of positive resection margins. Methods: From 2016 to 2018, 22 women with T1/T2 invasive breast cancer were enrolled for MWA prospectively in the guidance of BCS. US-guided MWA was performed under local anesthesia, followed by BCS and sentinel lymph node biopsy (SLNB) one week after ablation. Women who underwent palpation-guided BCS directly were included as control, and propensity score matching analysis was applied. Results: MWA was performed in 22 patients. Of the 21 MWA cases with effect information, the mean tumor size in US was 20.9 ± 6.2 mm (6-37 mm). Compared with control group (BCS directly), a lower rate of positive/close margins was observed in MWA guidance group (P = 0.018), and MWA caused a higher rate of accurate surgery (the largest margin ≤ 3 cm and the smallest margin ≥ 1mm, P = 0.042). Of these 21 patients treated with MWA, 18 were candidates for SLNB. And sentinel lymph nodes were successfully identified in all cases, and no recurrence was found with a mean follow-up of 23 months. Conclusion: For patients with T1/T2 breast cancer, the application of preoperative MWA could guide BCS accurately without impairing SLNB. Clinical trials with long-term results are required to validate MWA in the guidance for breast cancer excision. [ABSTRACT FROM AUTHOR]

Background: Contrast-enhanced ultrasound (CEUS) can provide angiogenesis information about breast lesions; however, its diagnostic performance in comparison with that of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has not been systematically investigated. This study aimed to evaluate the diagnostic efficacy of CEUS and DCE-MRI in mass-like and non-mass-like enhancement types of breast lesions. Material and Methods: A retrospective study was conducted on 252 patients with breast lesions who underwent CEUS and DCE-MRI before surgery between January 2016 and February 2020. Histopathological results were used as reference standards. All patients were classified into mass-like and non-mass-like enhancement lesion groups. The mass-like lesion group was further divided into three categories according to different sizes (group 1: < 10 mm, group 2: 10– 20 mm, and group 3: > 20 mm). Sensitivity, specificity, positive predictive value, negative predictive value, and receiver operating characteristic curve were analyzed to assess the diagnostic performance of these two modalities. Results: For mass-like breast lesions, DCE-MRI (Az=0.981) manifested better diagnostic performance than CEUS (Az=0.940) in medium-sized (10– 20 mm) tumors (Z=2.018, P=0.043), but both had similar diagnostic performance in smaller (< 10 mm) and larger (> 20 mm) tumors (P=0.717, P=0.394). For non-mass-like enhancement lesions, CEUS and DCE-MRI showed no significant difference (Z=1.590, P=0.119) and revealed good diagnostic performance (Az=0.859, Az=0.947) in differentiating the two groups. Conclusion: For mass-like breast lesions, DCE-MRI showed better diagnostic performance than CEUS in differentiating benign and malignant tumors of medium-sizes (10– 20mm) but not of smaller (< 10mm) and larger (> 20 mm) sizes. For non-mass-like lesions, both modalities showed similar diagnostic performance. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common malignancy among women worldwide. However, identifying effective biomarkers for the diagnosis and treatment of BC is challenging. Based on our previously developed 'humanized' mouse model of BC, microarray expression analysis was performed and multiple differentially expressed genes, including ribosomal protein (RP) L32, were screened. Recent reports have revealed that RPs are relevant to the development and progression of cancer. However, the expression and function of RPL32 in BC remains unknown. Therefore, in the present study, the role of RPL32 in the development of BC was explored. Immunohistochemical staining and reverse transcription-quantitative PCR were used, and it was found that RPL32 was upregulated in human BC tissues and cells. Cell Counting Kit-8, cell invasion and migration assays were performed, which demonstrated that RPL32 knockdown using lentivirus-delivered small interfering RNA inhibited the migration and invasion of BC cells in vitro and in vivo (nude mouse model). Moreover, western blotting showed that RPL32 knockdown decreased the expression levels of matrix metalloproteinase (MMP)-2 and MMP-9. Thus, the present findings indicated a potential oncogenic role of RPL32, suggesting that it may be a novel target for molecular targeted therapy in patients with BC. [ABSTRACT FROM AUTHOR]

Background: Male breast cancer is a rare malignant disease, accounting for <1% of all breast cancers. The treatment of male breast cancer is mainly extrapolated from the enormous literature and clinical experience in women. The objective of the current study was to assess the relationship between adjuvant chemotherapy and survival in a large population-based cohort of patients with early-stage male breast cancer.Methods: Men with invasive stage I to stage III breast cancer were identified in the Surveillance, Epidemiology, and End Results cancer database from 1990 to 2014. The effect of chemotherapy on survival was determined using multivariable Cox regression.Results: Of 2713 male patients enrolled, 1817 (66.9%) did not receive chemotherapy. Age, T classification, N classification, tumor grade, and progesterone receptor (PR) status were found to be strong predictors of chemotherapy administration. Chemotherapy was associated with a significant 26% reduction in all-cause mortality (P < .001) and a marginally significant 21% reduction in breast cancer-specific mortality (P = .085). For men with PR-negative breast cancer, use of chemotherapy was associated with improved breast cancer-specific survival (hazards ratio [HR], 0.50; 95% confidence interval [95% CI], 0.28-0.91 [P = .023]) and overall survival (HR, 0.54; 95% CI, 0.37-0.77 [P = .001]). However, chemotherapy did not improve the breast cancer-specific survival for all men with PR-positive tumors (P = .959); it was associated with improved overall survival (HR, 0.78; 95% CI, 0.66-0.92 [P = .004]) for men with PR-positive stage II and stage III breast cancer.Conclusions: Chemotherapy should be considered for men with PR-negative, nonmetastatic breast cancer and PR-positive, stage II and stage III breast cancer. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (NCT) is the standard treatment for patients with locally advanced breast cancer (LABC). The aim of this study was to verify this relationship, and to estimate the clinical value of aneuploid circulating endothelial cells (CECs) in LABC patients with different NCT responses. Methods: Breast cancer patients received an EC4-T4 NCT regimen. Peripheral blood mononuclear cells were obtained before NCT, and after the first and last NCT courses. A novel subtraction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) strategy was applied for detection of circulating rare cells (CRCs). CECs (CD45–/CD31+/DAPI+) and circulating tumor cells (CTCs) with different cytogenetic abnormalities related to chromosome 8 aneuploidy were analyzed in LABC patients subjected to NCT. Results: A total of 41 patients were enrolled. Firstly, CD31+/EpCAM+ aneuploid endothelial-epithelial fusion cells were observed in LABC patients. Further, aneuploid CECs in the peripheral blood showed a biphasic response during NCT, as they initially increased and then decreased, whereas a strong positive correlation was observed between aneuploid CECs and CTC numbers. Conclusion: We determined that aneuploid CEC dynamics vary in patients with different response to chemotherapy. Elucidating the potential cross-talk between CTCs and aneuploid CECs may help characterize the process associated with the development of chemotherapy resistance and metastasis. [ABSTRACT FROM AUTHOR]

This study aimed to retrospectively evaluate the circulating free DNA (cfDNA) level in patients with locally advanced breast cancer (LABC) having different neoadjuvant chemotherapy (NCT) responses and to investigate whether dynamic changes in cfDNA level could predict the effectiveness of NCT in patients with LABC. Data on 61 patients with LABC were included. NCT responses were evaluated using the response evaluation criteria. Blood samples were collected for cfDNA detection before treatment and after the first and eighth courses of chemotherapy. The Alu 111‐bp and 260‐bp fragment levels were evaluated by polymerase chain reaction, and the predictive value of the cfDNA level in the NCT response was determined. In vitro, the MCF‐7 and MCF‐7/ADR cell lines were applied to simulate the phenomenon of drug resistance and explain the underlying mechanism. The Alu 111‐bp level increased after the first NCT course (P =.014) and then remained high after NCT in the high‐R group (P =.047), but it remained steady in the low‐R group during NCT. A similar tendency in the Alu 260‐bp level was revealed in different groups. The ∆∆Ct value of Alu 260‐bp had good diagnostic efficiency in assessing predictive ability. The area under the curve for the ∆∆Ct1 and ∆∆Ct2 of Alu 260‐bp was 0.697 and 0.647, respectively. The cfDNA level was closely related to epirubicin‐induced apoptosis and changes in the Ki‐67 index in vitro. The elevation of cfDNA after one chemotherapy cycle was mediated by the apoptosis of tumor cells and related to the improved chemotherapy response. [ABSTRACT FROM AUTHOR]

Breast cancer has become the most common cancer in women, and nontriple negative breast cancer (non‐TNBC) accounts for 80–90% of all invasive breast cancers. Early detection, diagnosis, and treatment are considered key to a successful cure. Conventionally, breast imaging and needle core biopsy are used for detection and monitoring. However, small variations in volume might be ignored in imaging, and traditional biopsies are spatially and temporally limited, leading to a significant delay in cancer detection and thus prompting renewed focus on early and accurate diagnosis. In this article, we investigated whether there is an accurate molecule in peripheral blood that can help diagnose breast cancer. Similar to microRNAs, tRNA‐derived fragments (tRFs) have been reported to be involved in many pathological processes in breast cancer, but whether they can serve as candidate biomarkers for breast cancer remains unclear. Using high‐throughput sequencing technology, we identified 4,021 differentially expressed tRFs in normal and breast cancer cell lines, and eight tRFs were selected to establish a signature as a predictive biomarker of non‐TNBC. Furthermore, quantitative reverse‐transcriptase polymerase chain reaction was performed to verify the expression of the signature and analyze the correlation between dysregulated tRFs and breast cancer. The results indicated that tDR‐7816, tDR‐5334, and tDR‐4733 might be promising biomarkers. Through further bioinformatics analysis, we predicted that tDR‐7816 influences the xenobiotic metabolic processes that support the oncogenesis of breast cancer. In summary, our results provide a rationale for using circulating tDR‐7816 expression as a novel potential biomarker for the diagnosis of patients with early non‐TNBC. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs) intravasate into the bloodstream throughout early cancer stages, promoting metastasis. The tumor microenvironment plays a crucial role in disease progression and outcome. The aim of this prospective study was to investigate the associations of intratumoral and stromal tumor-infiltrating lymphocytes (TILs) with CTCs among patients receiving neoadjuvant chemotherapy (NAC). Methods: We analyzed CTCs in 30 patients with primary breast cancer before and after NAC. The numbers of intratumoral TILs (iTILs) and stromal TILs (sTILs) from pre-NAC formalin-fixed paraffin-embedded core biopsies and post-NAC surgical samples were analyzed. The associations of TILs with pathologic complete response (pCR) and outcome were also evaluated. Results: Of the 30 patients, pCR was achieved in nine (30.0%) patients. A total of 25 (83.3%) patients were CTC-positive before NAC, and eight (26.7%) patients were CTC-positive after NAC. Neither CTC detection before NAC nor CTC after NAC was predictive of pCR. Nevertheless, the presence of CTCs after NAC was significantly associated with early metastatic relapse (P = 0.049) and worse disease-free survival (P = 0.009). After NAC, total sTILs, CD4+ T cells, and CD8+ T cells were significantly correlated with CTC detection. Increased infiltration of sTILs and CD4+ T cells was also an unfavorable prognostic factor as measured by the rate of metastatic relapse. Conclusion: Detection of CTCs after NAC was positively associated with the metastatic relapse of breast cancer patients. Increased infiltration of sTILs after NAC was correlated with CTCs and was found to be an unfavorable prognostic factor. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common cancers in females. Since early detection can bring prognosis benefit, discovery of novel noninvasive biomarkers for BC diagnosis is in urgent need. In this four‐phase study, we profiled miRNA expression in plasma samples from a total of 257 BC patients and 257 normal controls (NCs). Exiqon miRNA qPCR panel was used to select candidate miRNAs in the screening phase which were further analyzed using qRT‐PCR in the following training, testing and external validation phases. Finally, we identified five plasma miRNAs (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) whose expression levels were significantly different between BC patients and NCs. A 5‐miRNA panel in plasma with high sensitivity and specificity was then constructed to detect BC. The areas under the receiver‐operating characteristic curves (AUCs) of the panel were 0.683, 0.966, 0.978 for the training, testing and external validation sets, respectively. Expression of the identified miRNAs was further analyzed among 32 pairs of BC tissue and the adjacent normal tissue samples as well as plasma‐derived exosome samples from 32 BC patients vs 32 NCs. Let‐7b‐5p was contrarily down‐regulated in BC tissue. In exosomes samples, only miR‐122‐5p was significantly up‐regulated as in plasma for BC patients. In conclusion, we identified a 5‐miRNA plasma panel (let‐7b‐5p, miR‐122‐5p, miR‐146b‐5p, miR‐210‐3p and miR‐215‐5p) that could serve as a promising biomarker for BC detection. [ABSTRACT FROM AUTHOR]

irculating tumor cells (CTCs) dissemination is involved in tumor metastasis and is an independent prognostic factor in patients with primary and metastatic breast cancer. Regulatory T cells (Tregs) and cluster of differentiation (CD)8+ T lymphocytes are the main types of immune cells in the tumor microenvironment and exert opposite roles on the progression and outcome of breast cancer. The aim of the present study was to evaluate the associations between CTCs and intratumoral/peritumoral Tregs and CD8+ T lymphocytes in breast cancer. Peripheral CTCs were detected by a multi‑marker quantitative polymerase chain reaction platform in 167 patients with invasive breast cancer. Intratumoral/peritumoral Tregs and CD8+ T lymphocytes were assessed by immunohistochemistry in 167 patients with invasive breast cancer to establish an association between these cell types and detection of peripheral CTCs. CTCs were detected in 55% of the patients with breast cancer. The prevalence of CTCs was positively associated with the number of intratumoral (P=0.002) and peritumoral Tregs (P=0.045), and the primary tumor size (P=0.012). This result was verified by analyzing intratumoral Tregs (P=0.044) and primary tumor size (P=0.044) with multivariate analysis, which indicated that the CTC‑positive rate increased with an increasing number of intratumoral Tregs and a larger tumor size In the multivariate analysis, other variables including menopause, tumor‑node‑metastasis stage and peritumoral Tregs were not associated with the prevalence of CTCs. The prevalence of CTCs was inversely and weakly associated with the number of peritumoral CD8+ T lymphocytes using the univariate analysis, however this result was not statistically significant (P=0.470). In conclusion, regulatory T cells and CD8+ T lymphocytes may be involved, at least in part, in the CTCs dissemination of breast cancer, whereby Tregs appear to exert the dominant effect. Furthermore, the role of Tregs in the progression of breast cancer may be mediated by suppressing the dissemination of CTCs, which is primarily determined by intratumoral Tregs. [ABSTRACT FROM AUTHOR]

Purpose: Novel noninvasive biomarkers with high sensitivity and specificity for the diagnosis of breast cancer (BC) are urgently needed in clinics. The aim of this study was to explore whether miRNAs from the miR-106a-363 cluster can be detected in the circulation of BC patients and whether these miRNAs can serve as potential diagnostic biomarkers.Methods: The expression of 12 miRNAs from the miR-106a-363 cluster was evaluated using qRT-PCR in 400 plasma samples (from 200 BC patients and 200 healthy controls (HCs)) and 406 serum samples (from 204 BC patients and 202 HCs) via a three-phase study. The identified miRNAs were further examined in tissues (32 paired breast tissues), plasma exosomes (from 32 BC patients and 32 HCs), and serum exosomes (from 32 BC patients and 32 HCs).Results: Upregulated levels of four plasma miRNAs (miR-106a-3p, miR-106a-5p, miR-20b-5p, and miR-92a-2-5p) and four serum miRNAs (miR-106a-5p, miR-19b-3p, miR-20b-5p, and miR-92a-3p) were identified and validated in BC. A plasma 4-miRNA panel and a serum 4-miRNA panel were constructed to discriminate BC patients from HCs. The areas under the receiver-operating characteristic curves of the plasma panel were 0.880, 0.902, and 0.858, and those of the serum panel were 0.910, 0.974, and 0.949 for the training, testing, and external validation phases, respectively. Two overlapping miRNAs (miR-106a-5p and miR-20b-5p) were consistently upregulated in BC tissues. Except for the expression of the plasma-derived exosomal miR-20b-5p, the expression patterns of exosomal miRNAs were concordant between plasma and serum, indicating the potential use of exosomal miRNAs as biomarkers.Conclusion: We identified four plasma miRNAs and four serum miRNAs from the miR-106a-363 cluster as promising novel biomarkers for the diagnosis of BC. [ABSTRACT FROM AUTHOR]

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death in females worldwide. Chemoresistance has been a major reason for the drug therapy failure. The present study performed a microarray analysis between MCF-7 and MCF-7/adriamycin (ADR) cells, and intended to identify long non-coding (lnc)RNA expression character in drug resistant breast cancer cells. MCF-7/ADR cells were induced from MCF-7 cells via pulse-selection with doxorubicin for 4 weeks, and the resistance to doxorubicin of ADR cells was confirmed by MTT assay. Microarray analysis was performed between MCF-7 and MCF-7/ADR cells. Total RNA was extracted from the two cell lines respectively and was transcribed into cDNA. The results of the microarray were verified by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Gene Ontology (GO) and pathways analysis were conducted to enrich the dysregulated lncRNAs presented in the microarray results. Compared to the MCF-7 cells, 8,892 lncRNAs were differentially expressed in MCF/ADR cells (absolute fold-change >2.0). A total of 32 lncRNAs were selected for RT-qPCR by fold-change filtering, standard Student's t-test, and multiple hypothesis testing. Among the dysregulated lncRNAs, AX747207 was prominent because its associated gene RUNX3 was previously reported to be relative to malignant tumor chemoresistance. GO analysis results also indicated some biological processes and molecular functions linked to chemoresistance. The pathway enrichment results provided some potential pathways associated with chemoresistance. In the present study, the authors intended to identify lncRNA expression character in drug resistant cell line MCF-7/ADR, corresponding to the parental MCF-7 cell line. In addition, the study identified the lncRNA AX747207, and its potential targeted gene RUNX3, may be related to chemoresistance in breast cancer. These results may new insights into exploring the mechanisms of chemoresistance in breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is the second leading cause of cancer‑associated mortality, and metastatic breast cancer is responsible for 90% of patient mortalities. Given that JWA represses the proliferation, invasion and metastasis of a number of other human tumor cells, including melanoma, esophageal, hepatocellular and gastric carcinomas, via mitogen‑activated protein kinase or integrin signaling, the present study investigated the expression and function of JWA in human breast cancers. The results showed that the expression level of JWA was significantly reduced in human primary breast cancers when compared with the paired adjacent tissues. Downregulating JWA enhanced, while overexpressing JWA suppressed, the migration and invasion abilities of the two breast cancer cell lines, MDA‑MB‑468 and MDA‑MB‑231, without affecting their proliferations in vitro. In addition, JWA negatively regulated the surface expression of CXCR4 in the two cell lines via proteasome degradation, though not via transcriptional inhibition. Functionally, normalizing the disturbed expressions of CXCR4 largely reversed the inhibitory effect of JWA on cell invasion. These data demonstrated that JWA suppressed the migration/invasion of breast carcinoma cells by downregulating the expression of CXCR4, and suggested that JWA may harbor prognostic and therapeutic potential in patients with breast cancer. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy (NCT) is the standard treatment for locally advanced breast cancer (LABC). Pathological complete response (pCR) is commonly used as a valid predictor of NCT long-term outcomes. Blood-based tumor biomarkers have the potential to predict response to NCT at early stage non-invasively. We believed plasma CCL5 could be a potential marker to predict NCT of LABC. Its efficiency and possible mechanism was studied in this work. Human Cytokine Antibody Microarray was applied to screen different cytokine concentration in plasma between low histological regression (Low-R) and high histological regression (High-R) patients. LABC patients were divided into two groups according to pathological reactivity. The concentration of plasma CCL5 in different groups was determined by ELISA analysis. CCK8 assay was performed to analyze epirubicin susceptibility of breast cancer cells. Transwell assay was performed to determine the effect of CCL5 on breast cancer cells’ migration and invasion. qRT-PCR and western blot were used to verify the EMT (epithelial-mesenchymal transition) markers in CCL5-treated and epirubicin-treated breast cancer cells. The concentration of plasma CCL5 of Low-R group was higher than High-R group before NCT. The plasma levels of CCL5 were significantly reduced after NCT in the group of high histological regression (High-R). Epirubicin susceptibility decreased in the breast cancer cells treated by recombinant CCL5. Migration and invasion were significantly enhanced in breast cancer cells treated by recombinant CCL5. E-cadherin expression was decreased whereas vimentin increased significantly in CCL5-treated breast cancer cells. The phosphorylation of ezrin in Y-567 and its downstream protein cortactin increased significantly in CCL5-treated breast cancer cells. Plasma CCL5 level could be a promised candidate to predict chemotherapy response of breast cancer. Plasma CCL5 plays an important role in EMT process of breast cancer. [ABSTRACT FROM AUTHOR]

Background: Minimally invasive therapies, such as microwave ablation (MWA), are widely used for the treatment of solid tumors. Previous studies suggest that MWA is feasible for the treatment of small breast cancer, and thermal ablation may induce adaptive antitumor immunity. However, the induced immune responses are mostly weak, and the immunomodulation effects of MWA in breast cancer are unclear. Immunostimulant OK-432 can induce tumor-specific T-cell responses and may augment the immunity induced by MWA.Methods: We treated 4T1 breast cancer bearing BALB/c mice with MWA, OK-432, MWA plus OK-432, or left without treatment. Survival time was evaluated with the Kaplan-Meyer method comparing survival curves by log-rank test. On day 25 after ablation, surviving mice received tumor rechallenge, and the rechallenged tumor volumes were calculated every 5 days. Immunohistochemistry and flow cytometry were used to evaluate the T-cell immune responses in ablated tissues and spleens. The tumor-specific immunity was assessed by enzyme-linked immunospot assays. Besides, the cytokine patterns were identified from enzyme-linked immunosorbent assay.Results: Microwave ablation plus OK-432 resulted in longer survival than single treatment and protect most surviving mice from tumor rechallenge. Both local and systemic T-cell responses were induced by MWA and were further enhanced by subsequent administration of OK-432. Moreover, the combination of MWA and OK-432 induced stronger tumor-specific immune responses than MWA alone. In addition, OK-432 and MWA synergistically promoted the production of Th1-type but not Th2-type cytokines, and polarized T-cell responses to Th1-dominant state.Conclusions: The T-cell immune responses were activated by MWA in breast cancer. Furthermore, the combination of MWA and OK-432 induced Th1-type response and elicited specific antitumor immunity. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to explore whether doxorubicin hydrochloric (DOX) combined with microwave ablation (MWA) is more effective at increasing tumour coagulation and prolonging end-point survival in a VX2 rabbit breast cancer model than each intervention individually. Methods: New Zealand white rabbits with VX2 tumours were placed into treatment groups as follows: MWA (20 W for 5 min and 40 W for 5 min), intravenous injection of 4 mg/kg DOX, and combined therapy. Tumours were analysed at 4 h and 24 h after treatment to determine the temporal quantities of cleaved caspase-3 and Hsp70 using immunohistochemical staining and Western blots. Tumour coagulation areas were compared at 24 h after treatment. Results: No significant difference in tumour coagulation was found between DOX-MWA and 40W-MWA (mean 4.52 cm2± 0.48 (SD), 4.08 cm2± 0.36, respectively;P >0.05). A significant difference between tumour coagulation was found for DOX-MWA and 20W-MWA (mean 4.52 cm2± 0.48 (SD), 1.69 cm2± 0.34 cm2, respectively;p <0.01). Cleaved caspase-3 and Hsp70 demonstrated low level expression at 4 h and 24 h in the DOX group. Cleaved caspase-3 showed low expression at the coagulation margin in the 20W-MWA group, was highly expressed in DOX-MWA group, and continued to increase with time. Hsp70 in the 20W-MWA group increased significantly at the coagulation margin but demonstrated low expression in the DOX-MWA group at 4 h and 24 h. The animals in the combined treatment group had a longer survival time (mean 78.33 days ± 8.07 SD) than the 20W-MWA group (mean 57.17 days ± 8.77,p <0.01) or the DOX group (mean 35.17 days ± 7.63,p <0.01). Conclusion: A combination of DOX and MWA could increase tumour coagulation and end-point survival better than single therapy, which had some connection with the elevated expression of cleaved caspase-3 and low Hsp70 expression at the coagulation margin. [ABSTRACT FROM AUTHOR]

Background: Women with triple negative breast cancers (TNBCs) have a poor prognosis due to lack of suitable targeted therapies. Changes in the protein glycosylation are increasingly being recognized as an important modification associated with cancer etiology. Methods: In an attempt to identify TNBC biomarkers with greater diagnostic and prognostic capabilities, hydrazide- based chemistry method combined with LC-MS/MS were used to purify and identify N-linked glycopeptides or glycoproteins of tissues from TNBC patients. Results: A total of 550 unique N-linked glycoproteins were identified, among these proteins, 72 unique N-linked glycoproteins were significantly regulated in tumor tissues, of which 56 proteins were upregulated and 16 proteins were downregulated. To assess the validity of the results, three selected proteins including Vascular endothelial growth factor receptor 1, Insulin receptor, Tissue factor pathway inhibitor were selected for western blot analysis, and these proteins were found as potential biomarkers of TNBC. The top three pathways of differentially expressed glycoproteins participated in were caveolar-mediated endocytosis signaling, agrin interactions at neuromuscular junction and LXR/RXR activation. Conclusion: This work provides potential glycoprotein markers to function as a novel tissue-based biomarker for TNBC. © 2016 The Author(s) Published by S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Breast cancer remains a world-wide challenge, and additional anti-cancer therapies are still urgently needed. Emerging evidence has demonstrated the potent anti-tumor effect of biguanides, among which phenformin was reported to potentially be a more active anti-cancer agent than metformin. However, little attention has been given to the role of phenformin in breast cancer. In this study, we reveal the role of phenformin in cell death of the MCF7, ZR-75-1, MDA-MB-231 and SUM1315 breast cancer cell lines. The respective IC50 values of phenformin in MCF7, ZR-75-1, MDA-MB-231 and SUM1315 cells were 1.184±0.045 mM, 0.665±0.007 mM, 2.347±0.010 mM and 1.885±0.015 mM (mean± standard error). Phenformin induced cell cycle change and apoptosis in breast cancer cells via the AMPK/mTOR/p70s6k and MAPK/ERK pathways. Interestingly, phenformin induced MET (mesenchymal-epithelial transition) and decreased the migration rate in breast cancer cell lines. Furthermore, our results suggest that phenformin inhibits breast cancer cell metastasis after intracardiac injection into nude mice. Taken together, our study further confirms the potential benefit of phenformin in breast cancer treatment and provides novel mechanistic insight into its anti-cancer activity in breast cancer. [ABSTRACT FROM AUTHOR]

Aim Blood group is an important risk factor for some malignancies, including pancreatic and stomach cancer. However, it is unclear whether the risk of breast cancer is higher in any specific ABO blood type. Methods We searched the electronic database of Pub Med, EMBASE, China National Knowledge Infrastructure and the VIP Chinese Journal of Science and Technology for case-control studies about blood type and breast cancer incidence, and a meta-analysis was conducted. Results Fourteen studies were eligible for assessment on the association of breast cancer with different blood types, including 9665 breast cancer patients and 244 768 controls. Relative to blood type O, women with blood type A (odds ratio ( OR) = 1.115, 95% confidence interval ( CI) 0.992-1.254), B ( OR = 0.983, 95% CI 0.915-1.056) and AB ( OR = 1.042, 95% CI 0.881-1.231) had the same breast cancer risk. The risk for women with Rhesus-positive ( Rh+) was the same as those with Rh-negative ( Rh-) ( OR = 0.948, 95% CI 0.667-1.348). Among Caucasians, the OR of blood type A was 1.066 (95% CI, 1.001-1.134, P = 0.522 for heterogeneity). Conclusion This meta-analysis suggests Caucasians with blood type A may have a higher risk of breast cancer than other Caucasians. No association was found in any other blood type or any other population. Similarly, the Rh factor had no association with the risk of breast cancer. [ABSTRACT FROM AUTHOR]

Breast cancer ( BC) is one of the most common cancers in women, and it can often metastasize to the bone. The mechanism of BC bone metastasis remains unclear and requires in-depth investigation. In a previous study, we found the expression of matrix metalloproteinase 2 ( MMP2) to be significantly more pronounced at metastatic bone sites than at orthotopic sites. Micro RNA expression profiling showed miR-106b to be markedly downregulated during BC bone metastasis. However, the specific manner in which MMP2 and miR-106b are involved in the BC bone metastasis is still unclear. In the present study, we found MMP2 expression in orthotopic tumor tissue to be related to the risk of bone metastasis in BC patients. MiR-106b levels in orthotopic tumor tissue showed a negative correlation with MMP2 expression and breast cancer bone metastasis. MMP2 was shown to be a direct target of miR-106b. Both gain- and loss-of-function studies showed that MMP2 could promote the migration and invasion of BC cells and that miR-106b could suppress both. The blockage of MMP2 by RNA interference mimicked the anti-migration and anti-invasion effects of miR-106b, and introduction of MMP2 antagonized the function of miR-106b. MMP2 was also found to regulate the ERK signaling cascade and so adjust the bone microenvironment to favor osteoclastogenesis and bone metastasis. These results suggest that MMP2 upregulation plays an important role in BC bone metastasis through ERK pathways, and miR-106b directly regulates MMP2 expression. The miR-106b/ MMP2/ ERK pathway may be a promising therapeutic target for inhibiting BC bone metastasis. [ABSTRACT FROM AUTHOR]

Genetic variants may influence miRNA–mRNA interaction through modulate binding affinity, creating or destroying miRNA-binding sites. Twenty-four single nucleotide polymorphisms (SNPs) that were predicted to affect the binding affinity of breast cancer-related miRNAs to 3′-untranslated regions (UTR) of known genes were genotyped in 878 breast cancer cases and 900 controls in Chinese women. Three promising SNPs (rs10494836, rs10857748 and rs7963551) were further validated in additional 914 breast cancer cases and 967 controls. The variant allele (C) of rs7963551 at 3′-UTR of RAD52 showed a consistently reduced breast cancer risk in two stages with a combined odds ratio (OR) of 0.84 [95% confidence interval (CI) = 0.75–0.95], which was more prominent among women with early age at first live birth (OR = 0.71, 95% CI = 0.58–0.87). A significant interaction was observed between rs7963551 and age at first live birth on breast cancer risk (P for interaction = 0.04). Luciferase activity assay showed a higher expression level for rs7963551 C allele as compared with A allele (P = 5.19×10–3 for MCF-7 cell lines), which might be due to a reduced inhibition from a weakened binding capacity of miRNA to 3′-UTR of RAD52 harboring C allele. These findings indicate that rs7963551 located at hsa-let-7 binding site may alter expression of RAD52 through modulating miRNA–mRNA interaction and contribute to the development of breast cancer in Chinese women. [ABSTRACT FROM AUTHOR]

Breast cancer usually initially metastases to the sentinel lymph nodes (SLNs). Recent studies have demonstrated that tumor cells induce SLN lymphangiogenesis before metastasis in several malignancies. In addition, tumor-derived VEGF-C or VEGF-D may induce lymphangiogenesis and promote lymph node metastasis. To explore the mechanisms of lymph node metastasis in breast cancer, we investigated whether primary tumors induce SLN lymphangiogenesis before metastasis and determined the function of tumor-derived VEGF-C and VEGF-D in SLN lymphangiogenesis. Expression of VEGF-C and VEGF-D was examined using immunohistochemistry in 63 primary breast tumors. No significant relationships between VEGF-C and VEGF-D ( P = 0.420), and VEGF-C or VEGF-D expression and clinical parameters (age, tumor size, grade, hormonal receptor status, her-2 status) were observed ( P > 0.05). Expression of the lymphatic-specific markers VEGFR- 3, Prox- 1 and LYVE- 1 was measured using quantitative real-time RT-PCR in uninvolved SLNs from 63 patients and compared to control lymph nodes from patients with benign breast disease. Expression of Prox- 1 and LYVE- 1 mRNA was significantly higher in uninvolved SLNs from breast cancer patients than that in control lymph nodes ( P < 0.01). Interestingly, expression of VEGFR- 3, Prox- 1 and LYVE- 1 was significantly higher in SLNs from patients with high VEGF-C-expressing tumors than low VEGF-C-expressing tumors ( P < 0.05), but not VEGF-D-high-expressing tumors ( P > 0.05). This study demonstrates that primary breast tumors induce SLN lymphangiogenesis before metastasis occurs and that tumor-derived VEGF-C, but not VEGF-D, plays an important role in SLN lymphangiogenesis in breast cancer. [ABSTRACT FROM AUTHOR]

Abstract: We sought to determine whether STAT3 mediated tamoxifen resistance of breast cancer stem cells in vitro. The capacities for mammosphere formation and STAT3 expression of CD44+CD24−/low MCF-7 and MCF-7 were observed. The CD44+CD24−/low subpopulation ratio and its sensitivity to adriamycin were analyzed in MCF-7 and TAM resistant (TAM-R) cells. Cell cycle, apoptosis, STAT3 and phospho-STAT3 changes were observed af-ter treatment with tamoxifen. Small interference RNA-mediated knockdown of STAT3 in TAM-R cells was also performed. CD44+CD24−/low MCF-7 showed higher capacities for mammosphere formation and STAT3 expression than total MCF-7. The CD44+CD24−/low subpopulation was also upregulated in TAM-R cells with less sensitivity to adriamycin than MCF-7. Cell cycle changes, anti-apoptotic effects and STAT3 changes were also found. Mean-while, the knock-down of STAT3 in TAM-R resulted in an increase in sensitivity to tamoxifen. It is concluded that STAT3 plays an essential role in breast cancer stem cells, which correlated with tamoxifen resistance. [Copyright &y& Elsevier]

Background: Genome-wide association studies (GWAS) have identified several breast cancer susceptibility loci, and one genetic variant, rs11249433, at 1p11.2 was reported to be associated with breast cancer in European populations. To explore the genetic variants in this region associated with breast cancer in Chinese women, we conducted a two-stage finemapping study with a total of 1792 breast cancer cases and 1867 controls. Methodology/Principal Findings: Seven single nucleotide polymorphisms (SNPs) including rs11249433 in a 277 kb region at 1p11.2 were selected and genotyping was performed by using TaqManH OpenArrayTM Genotyping System for stage 1 samples (878 cases and 900 controls). In stage 2 (914 cases and 967 controls), three SNPs (rs2580520, rs4844616 and rs11249433) were further selected and genotyped for validation. The results showed that one SNP (rs2580520) located at a predicted enhancer region of SRGAP2 was consistently associated with a significantly increased risk of breast cancer in a recessive genetic model [Odds Ratio (OR) = 1.66, 95% confidence interval (CI) = 1.16-2.36 for stage 2 samples; OR = 1.51, 95% CI = 1.16-1.97 for combined samples, respectively]. However, no significant association was observed between rs11249433 and breast cancer risk in this Chinese population (dominant genetic model in combined samples: OR = 1.20, 95% CI = 0.92-1.57). Conclusions/Significance: Genotypes of rs2580520 at 1p11.2 suggest that Chinese women may have different breast cancer susceptibility loci, which may contribute to the development of breast cancer in this population. [ABSTRACT FROM AUTHOR]

Interleukin-1β (IL-1β), which is involved in inflammatory and immunological responses, plays an important role in the development and progression of breast cancer. Three functional single nucleotide polymorphisms (SNPs) identified in IL-1β gene are thought to influence breast cancer risk. The results of the association between IL-1β polymorphisms and breast cancer remain inconsistent. Therefore, we conducted a meta-analysis of eight case-control studies with rs1143627 (T > C), rs16944 (C > T), and rs1143634 (C > T). We found that the variant CC genotype of rs1143627 was associated with a significantly increased breast cancer risk (CC vs. TT: OR = 1.37, 95% CI = 1.10-1.70, P = 0.22 for heterogeneity; the recessive model CC vs. TT/TC: OR = 1.40, 95% CI = 1.17-1.67, P = 0.49 for heterogeneity). For rs16944 (C > T) and rs1143634 (C > T), no significant associations were found in all genetic models. In conclusion, the present meta-analysis suggests that rs1143627 is associated with breast cancer risk. [ABSTRACT FROM AUTHOR]