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BACKGROUND: Here, we carried out an extensive meta-analysis to investigate the effectiveness of the use of axillary reverse mapping (ARM) during axillary lymph node dissection (ALND) in preventing breast cancer-related lymphedema (BCRL). METHODS: Database searches to identify relevant randomized controlled trials (RCTs) were performed of MEDLINE (PubMed), Web of Science, Embase, and the Cochrane Library. Eligible articles with a publication date from database establishment to December 2020 were retrieved by combining keywords including: “breast cancer”, “breast carcinoma”, “breast neoplasm”, “axillary reverse mapping”, “axillary lymph node dissection”, “lymphatic arm drainage”, and “lymphedema”. Independent data extraction was conducted, and Review Manager (version 5.3) was used for statistical analyses. RESULTS: Five eligible RCTs were included in the meta-analysis. A total of 37 patients suffered arm lymphedema (37/786, 4.71%) in the experimental group (ARM during ALND), compared with 164 arm lymphedemas (164/873, 18.79%) in the control group (ALND alone). The results showed that ARM during ALND was superior to ALND alone in reducing the incidence of BCRL [OR =0.20, 95% confidence intervals (CI): 0.13–0.29, P

Recent reports showed that haematological and neurological expressed 1‐like (HN1L) gene participated in tumorigenesis and tumour invasion. However, the expression and role of HN1L in breast cancer remain to be investigated. Here, bioinformatics, western blot and immunohistochemistry were used to detect the expression of HN1L in breast cancer. Wound healing, transwell assay, immunofluorescence assay and mass spectrum were used to explore the role and mechanism of HN1L on the migration and invasion of breast cancer, which was confirmed in vivo using a nude mice model. Results showed that HN1L was significantly over‐expressed in breast cancer tissues, which was positively correlated with M metastasis of breast cancer patients. Silencing HN1L significantly inhibited the invasion and metastasis of breast cancer cells in vitro and lung metastasis in nude mice metastasis model of breast cancer. Mechanistically, HN1L interacted with HSPA9 and affected the expression of HMGB1, playing a key role in promoting the invasion and metastasis of breast cancer cell. These results suggested that HN1L was an appealing drug target for breast cancer.

Background More and more studies show that platelets are closely related to the occurrence and development of tumors. This study aims to explore the predictive value of peripheral blood platelet count on the prognosis of breast cancer patients with ipsilateral supraclavicular lymph node (ISLN) metastasis. Methods Eighty-five breast cancer patients with ISLN metastasis in the Affiliated Cancer Hospital of Zhengzhou University were collected retrospectively in this study. Chi-square test was used to analyze the correlation between clinical pathological data and platelet count. DFS rate was estimated by K-M curve and Log Rank test was performed. Univariate and multivariate Cox regression were used to determine the prognostic value of platelets. Time-dependent Cox regression was used to further analyze the correlation between peripheral blood platelets and prognosis to determine the stability of the results. Results The pathological complete response rate of ISLN after neoadjuvant chemotherapy (NAC) was 51.8%. Platelet count was correlated with PR status of breast cancer at first visit (P=0.01). After a median follow-up of 30 months, multivariate Cox analysis showed that high platelet count (HR=3.18, 95% CI=1.13-8.93, P=0.028), premenopausal status (HR=0.40, 95% CI=0.17-0.97, P=0.043), and ISLN pathological failure (HR=0.25 95%, CI=0.10-0.62, P

BACKGROUND: Breast cancer (BC) is a common tumor that seriously affects women’s physical/mental health and even life. BC invasion and metastasis are still the main causes of mortality in BC patients. Exosomal long non-coding RNAs (exo-lncRNA) play an important role in cell communication and can help to understand better the physiological and pathological conditions that result from BC. This study investigates new potential targets and functions of the expression profiles of exo-lncRNAs in BC patients through high-throughput screening and bioinformatics. METHODS: Samples were collected from two BC patients and one healthy subject. The serum exosomal RNAs were subsequently purified, and a library was established for quality inspection and sequencing. The resultant data was compared with the reference data to obtain the differential expression of exo-lncRNAs, and predict the target genes. To obtain the final results, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to annotate the function and pathway of the differentially expressed genes. RESULTS: After a comprehensive comparison of the BC patients and healthy subjects, we discovered five up-regulated exo-lncRNAs and six down-regulated exo-lncRNAs of interest. Combining our results with a literature review and screening, we found that VIM-AS1, SNHG8, and ELDR play a role in the progression of BC, with VIM-AS1 predicting 35 target miRNAs; SNHG8 predicting 12 target miRNAs, and ELDR predicting 24 target miRNAs. Target prediction considered that the target gene of VIM-AS1 was VIM and that the target gene of SNHG8 was PRSS12. GO enrichment analysis showed that VIM mainly played a role in cell processes, biological regulation, metabolic regulation, and molecular adhesion, while PRSS12 was enriched through cell metabolism, catalytic activity, and hydrolase activity. KEGG pathway enrichment results also indicated how the VIM protein functions in cancer development through the viral infection signaling pathway and miRNA signaling pathway. CONCLUSIONS: There is a significant difference in the expression profiles of serum exo-lncRNAs between BC patients and healthy individuals. This may be closely related to BC’s occurrence, development, and metastasis, and therefore provides a theoretical basis for more in-depth studies into exo-lncRNA.

Background Previous studies have reported poor survival rates in inflammatory breast cancer (IBC) patients than non-inflammatory local advanced breast cancer (non-IBC) patients. However, until now, the survival rate of IBC and other T4 non-IBC (T4-non-IBC) patients remains unexplored. Methods Surveillance, Epidemiology, and End Results (SEER) database was searched to identify cases with confirmed non-metastatic IBC and T4-non-IBC who had received surgery, chemotherapy, and radiotherapy between 2010 and 2015. IBC was defined as per the American Joint Committee on Cancer (AJCC) 7th edition. Breast Cancer-Specific Survival (BCSS) was estimated by plotting the Kaplan-Meier curve and compared across groups by using the log-rank test. Cox model was constructed to determine the association between IBC and BCSS after adjusting for age, race, stage of disease, tumor grade and surgery type. Results Out of a total of 1986 patients, 37.1% had IBC and mean age was 56.6 ± 12.4. After a median follow-up time of 28 months, 3-year BCSS rate for IBC and T4-non-IBC patients was 81.4 and 81.9%, respectively (log-rank p = 0.398). The 3-year BCSS rate in HR−/HER2+ cohort was higher for IBC patients than T4-non-IBC patients (89.5% vs. 80.8%; log-rank p = 0.028), and in HR−/HER2- cohort it was significantly lower for IBC patients than T4-non-IBC patients (57.4% vs. 67.5%; log-rank p = 0.010). However, it was identical between IBC and T4-non-IBC patients in both HR+/HER2- (85.0% vs. 85.3%; log-rank p = 0.567) and HR+/HER2+ (93.6% vs. 91.0%, log-rank p = 0.510) cohorts. After adjusting for potential confounding variables, we observed that IBC is a significant independent predictor for survival of HR−/HER2+ cohort (hazards ratio [HR] = 0.442; 95% CI: 0.216–0.902; P = 0.025) and HR−/HER2- cohort (HR = 1.738; 95% CI: 1.192–2.534; P = 0.004). Conclusions Patients with IBC and T4-non-IBC had a similar BCSS in the era of modern systemic treatment. In IBC patients, the HR−/HER2+ subtype is associated with a better outcome, and HR−/HER2- subtype is associated with poorer outcomes as compared to the T4-non-IBC patients.

Neutrophils and lymphocytes are key regulators of breast cancer (BC) development and progression. Neutrophil to lymphocyte ratio (NLR) values have been found to offer clear prognostic utility when evaluating BC patients. In this study, we sought to determine whether BC patient baseline NLR values are correlated with pathological complete response (pCR) following neoadjuvant chemotherapy (NCT) treatment. In total, 346 BC patients underwent NCT at our hospital from January 1, 2014 to October 31, 2019, and data pertaining to these patients were retrospectively analyzed. Correlations between clinicopathological characteristics and pCR rates were assessed via multivariate logistic regression analyses. A predictive scoring model was used to gauge the likelihood of pCR based upon regression coefficient (β) values for each significant variable identified through these analyses. NLR cut-off values suitable for identifying patients likely to achieve pCR following NCT treatment were calculated using receiver operating characteristic (ROC) curves. All patients in the present study were females with a median age of 48 years old (range 22–77). An optimal NLR cut-off value of 1.695 was identified and was associated with respective sensitivity and specificity values of 63.6% and 45.5%. We found that higher NLR values were significantly associated with younger age, premenopausal status, and non-pCR status. Logistic regression analyses indicated that NLR, tumor size, hormone receptor (HR) status, and Ki-67 expression were all independent predictors of pCR. The area under the curve (AUC) for the resultant predictive scoring model was 0.705, and this model was assessed via K-fold cross-validation (k = 10) and bootstrapping validation, yielding respective AUC values of 0.68 and 0.694. Moreover, the incorporation of NLR into this predictive model incrementally improved its overall prognostic value relative to that of a model not incorporating NLR (AUC = 0.674). BC patients with a lower baseline NLR are more likely to exhibit pCR following NCT treatment, indicating that NLR may be a valuable biomarker for BC patient prognostic evaluation and treatment planning. Overall, our results demonstrate that this NLR-based predictive model can efficiently predict NCT efficacy in early BC patients with a high degree of accuracy.

BACKGROUND: Inflammatory tumor microenvironment is closely related to cancer. In this study, we mainly explore the predictive value of inflammatory markers for pathological response of ipsilateral supraclavicular lymph nodes (ISLN) and for prognosis in breast cancer with ISLN metastasis after neoadjuvant chemotherapy (NAC). METHODS: In this study, 117 breast cancer patients with ISLN metastasis were collected from the Affiliated Hospital of Zhengzhou University. The best cut-off value was determined by using the receiver operating characteristics (ROC) curve. Chi-square test and binary Logistic regression were used to analyze the correlation between clinical pathological data and pathological response of ISLN and to determine independent predictors. Correlation analysis between inflammatory markers and prognosis used time-dependent COX regression. RESULTS: The pathological complete response (pCR) rate of ISLN after NAC was 64.4%. Multivariate analysis showed that breast pCR (OR 9.67, 95% CI: 2.64–35.31, P

Triple-negative breast cancer (TNBC) has a high degree of malignancy. The endothelin B receptor (EDNRB) serves an important role in the occurrence and development of cancer. The present study aimed to investigate the prognostic value of EDNRB in TNBC. A total of 99 cases of TNBC were collected from the Henan Cancer Hospital database and 159 cases of TNBC were collected from The Cancer Genome Atlas database. A χ2 test was used to analyze the association between EDNRB and clinicopathological data. Kaplan-Meier analysis and multivariate Cox regression analysis were used to analyze the association between EDNRB and prognosis, and to establish two models. The discrimination degree of the models was evaluated using time-dependent receiver operating characteristic curves and concordance index (C-index), whereas the accuracy and net benefit of the models were evaluated using integrated discriminant improvement (IDI) and decision curves. EDNRB expression was low in TNBC samples (P

This study aims to investigate clinical significance of topoisomerase 2A (TOP2A) expression and TOP2A gene change in operable invasive breast cancer. This is a retrospective analysis, which includes 256 patients diagnosed as operable invasive breast cancer. All postoperational waxed specimens were subjected to resectioning for staining. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2), KI-67, TOP2A expression, and TOP2A gene changes were detected by immunohistochemistry (IHC) and fluorescent in situ hybridization technique (FISH), respectively. Correlation between TOP2A expression and clinicopathological characteristics was also investigated. Effects of TOP2A protein or gene changes on survival rate were detected. Results indicated that 165 were TOP2A positive (64.5 %), and 31 were gene amplification positive (12.1 %). Positive rate of TOP2A expression showed significant correlations with ER, KI-67, and HER-2. The difference of 5-year overall survival (OS) between TOP2A-positive and TOP2A-negative groups did not reach statistical significance (OS: P = 0.321, 85.9 vs. 79.6 %; disease-free survival [DFS]: P = 0.247, 83.3 vs. 75.3 %). Five-year OS in TOP2A amplification group was 68.8 %, which is lower than deficiency and control group (P > 0.05). Subgroup analysis showed no significant differences of OS and DFS either between TOP2A-positive and TOP2A-negative groups or between TOP2A amplification and control group in population of patients with HER-2 amplification, triple negative breast cancer, or hormone-positive breast cancer. In conclusion, positive rate of TOP2A expression correlates significantly with ER, KI-67, and HER-2. However, prognostic significance of either TOP2A expression or TOP2A gene changes in breast cancer and its various subtypes is limited.

BACKGROUND: Breast cancer with ipsilateral supraclavicular lymph node metastasis is one of the indicators of poor prognosis. Patients who attain pathologic complete response in breast and axillary sites have improved survival and are highest in aggressive HR–HER2– and HER2-positive tumor subtypes. However, there is no study on the related factors and prognostic value of supraclavicular pathologic complete response in breast cancer after neoadjuvant chemotherapy. The aim of our work was to investigate the factors and prognostic significance of pathologic complete response of ipsilateral supraclavicular lymph node metastasis in breast cancer after neoadjuvant chemotherapy. METHODS: A total of 214 patients with breast cancer who had primary ISLN metastasis, receiving NAC and subsequent ISLN dissection, were retrospectively and consecutively reviewed. Univariate and multivariate analyses were performed using χ(2) test and the logistic regression model, and the prognosis was analyzed by Kaplan-Meier curve. RESULTS: All patients included were women who were 26–74 years old. The rate of supraclavicular pathologic complete response (pCR) was 53.7%. Multivariate analysis showed that the expression of Ki67, breast pCR, and axillary pCR were independent predictors of supraclavicular pCR (P

The purpose of the present study was to determine the tissue and plasma levels of microRNA (miR)-155 and miR-31 in 67 patients with invasive intraductal breast cancer and their correlation with the clinicopathological characteristics. Using a quantitative real-time-PCR (qRT-PCR) assay, it was demonstrated that the plasma levels of miR-155 and miR-31 in patients were 6- and 5-fold higher than those in healthy individuals, respectively (P0.05). The expression levels of miR-155, but not miR-31, were inversely correlated with estrogen receptor (ER) and progesterone receptor (PR) expression (ER, r=−0.353, P=0.003; PR, r=−0.357, P=0.003). The tissue and plasma levels of miR-155 and miR-31 were not correlated with epidermal growth factor receptor-2 (HER-2) expression levels. Furthermore, high levels of plasma miR-155 and miR-31 were identified in the tumors of TNM stage II, lymph node metastasis 0–3 and tumor sizes of 2–5 cm in patients who were aged over 52 years. miR-155 was mainly expressed in patients with a pathology score of 3 for ER or PR expression; miR-31 expression was higher in patients with a pathology score of 2. These results suggest that miR-155 and miR-31 are differentially expressed in breast cancer patients. Their correlation with the clinicopathological characteristics may aid the diagnosis and treatment of invasive intraductal breast cancer.

Background Restin belongs to MAGE superfamily and is known as MAGE H1. Restin was firstly cloned from HL-60 cells treated with all-trans retinoic acid (ATRA). Previous studies showed a pro-apoptotic role of Restin in several cell lines. However, little information is available on its expression patterns and functions in vivo. Our study was performed to detect if Restin plays a role in breast cancer cells in vitro and in vivo. Methods and results Real-time PCR and western blot were conducted to detect Restin expression in multiple breast cancer cell lines and Restin level was negatively related with cell motility. Restin overexpression and knockdown stable cell lines were established by transducing lentivirus into MCF-7 and MDA-MB-231 cells. Cell morphology, wound closure assay, transwell migration and invasion assays were performed to detect if Restin inhibited EMT. Our data showed that Restin overexpressed cells exhibited classical epithelial cell morphology, and Restin overexpression resulted in activation of epithelial markers and suppression of mesenchymal markers, and inhibition of cell migration and invasion. Tumor xenograft model was used to characterize the biological functions of Restin in vivo. We found that Restin overexpression led to reduced lung metastasis. Real-time PCR, western blot, luciferase assay and ChIP assay were performed to identify the potential targets of Restin and the underlying molecular mechanisms. Among several master regulators of EMT, only ZEB1/2 levels were dramatically inhibited by Restin. Unexpectedly, Restin indirectly regulated ZEB1/2 expression at post-transcriptional level. We further identified mir-200a/b, well-characterized mediators controlling ZEB1/2 expression, were transcriptionally activated by Restin and the regulation was dependent on the p53 binding site in mir-200b/a/429 promoter. Further mechanical studies demonstrated Restin interacted with p73, one of p53 family members, which contributed to Restin-mediated activation of mir-200a/b and suppression of ZEB1/2. Conclusions Taken together, our results suggest that Restin inhibits EMT and tumor metastasis by controlling the expression of the tumor metastasis suppressor mir-200a/b via association with p73. Our findings not only establish a mechanistic link between Restin, EMT and tumor metastasis, but also provide strong evidence supporting the notion that MAGE Group II proteins may exert a tumor suppressive effect in vivo. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0370-9) contains supplementary material, which is available to authorized users.