Clinical Stage Of Breast Cancer Research Articles

Radiomics Analysis of Contrast-Enhanced Breast MRI for Optimized Modelling of Virtual Prognostic Biomarkers in Breast Cancer.

Breast cancer clinical stage and nodal status are the most clinically significant drivers of patient management, in combination with other pathological biomarkers, such as estrogen receptor (ER), progesterone receptor or human epidermal growth factor receptor 2 (HER2) receptor status and tumor grade. Accurate prediction of such parameters can help avoid unnecessary intervention, including unnecessary surgery. The objective was to investigate the role of magnetic resonance imaging (MRI) radiomics for yielding virtual prognostic biomarkers (ER, HER2 expression, tumor grade, molecular subtype, and T-stage). Patients with primary invasive breast cancer who underwent dynamic contrast-enhanced (DCE) breast MRI between July 2013 and July 2016 in a single center were retrospectively reviewed. Age, N-stage, grade, ER and HER2 status, and Ki-67 (%) were recorded. DCE images were segmented and Haralick texture features were extracted. The Bootstrap Lasso feature selection method was used to select a small subset of optimal texture features. Classification of the performance of the final model was assessed with the area under the receiver operating characteristic curve (AUC). Median age of patients (n = 209) was 49 (21-79) years. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of the model for differentiating N0 vs N1-N3 was: 71%, 79%, 76%, 74%, 75% [AUC = 0.78 (95% confidence interval (CI) 0.72-0.85)], N0-N1 vs N2-N3 was 81%, 59%, 24%, 95%, 62% [AUC = 0.74 (95% CI 0.63-0.85)], distinguishing HER2(+) from HER2(-) was 79%, 48%, 34%, 87%, 56% [AUC = 0.64 (95% CI 0.54-0.73)], high nuclear grade (grade 2-3) vs low grade (grades 1) was 56%, 88%, 96%, 29%, 61% [AUC = 0.71 (95% CI 0.63-0.80)]; and for ER (+) vs ER(-) status the [AUC=0.67 (95% CI 0.59-0.76)]. Radiomics performance in distinguishing triple-negative vs other molecular subtypes was [0.60 (95% CI 0.49-0.71)], and Luminal A [0.66 (95% CI 0.56-0.76)]. Quantitative radiomics using MRI contrast texture shows promise in identifying aggressive high grade, node positive triple negative breast cancer, and correlated well with higher nuclear grades, higher T-stages, and N-positive stages.

Impact of COVID-19 on the clinical staging of breast cancer: A cross-sectional study

Following the declaration of COVID-19 as a pandemic in February 2020, one of the most important public health impacts was the decrease in demand for screening mammography, with a consequent impact on the early diagnosis of breast cancer. Therefore, the aim of this study was to compare the initial clinical staging of women with breast cancer in the pre-pandemic and pandemic periods at a reference cancer hospital in southern Brazil. We performed a retrospective cross-sectional study with a database of surgical procedures on the female breast, comparing the years 2019 and 2020. A total of 1733 surgical procedures for diagnostic and curative purposes were evaluated. Among these patients, 491 (49.2 %) were diagnosed with breast cancer in 2019 and 335 (45.5 %) in 2020. We excluded 907 patients due to benign diagnoses, carcinoma in situ, recurrence, presence of metastases, missing data, and other findings. When comparing 2019 and 2020, we found no significant difference in clinical staging or tumor phenotype. The median time in days between mammography and first treatment was also similar in both years. However, we observed a higher frequency of lobular histologies and neoadjuvant therapy as first treatment choice in the pandemic year. In conclusion, there was no significant difference in clinical staging between women diagnosed with breast cancer before and during the pandemic.

The impact of COVID-19 on patients diagnosed with melanoma, breast, and colorectal cancer

BackgroundThe COVID-19 pandemic impacted healthcare resource allocation and utilization of preventative medical services. It is unknown if there is resultant stage migration of melanoma, breast, and colorectal cancer when comparing extended time periods before and after the pandemic onset. MethodsA retrospective cohort study of melanoma, breast, and colorectal cancer patients was completed. Clinical and pathological staging was compared utilizing 12 and 22-month timeframes before and after the pandemic outbreak. ResultsBetween the 22-month pre- and post-COVID-19 groups, breast cancer clinical stage T2 significantly increased, and pathological stage 2 decreased. Colorectal cancer clinical stage T1 decreased, stage T4 increased, and stage 0 decreased in the 22-month groups. In the 12-month groups, melanoma clinical stage T1 increased, and colorectal cancer clinical stage N2 increased. ConclusionsEvaluating extended timeframes beyond the immediate pre- and post-COVID-19 period revealed significant increases in clinical staging of breast and colorectal cancer, suggesting advanced disease is becoming more evident as time progresses.

Abstract P3-05-53: IMPACT OF THE BODY MASS INDEX (BMI) ON THE SURVIVAL OF BREAST CANCER WOMEN WHO ACHIEVED A COMPLETE PATHOLOGICAL RESPONSE (pCR) AFTER NEOADJUVANT CHEMOTHERAPY (NACT) IN BRAZIL

Abstract Introduction Breast cancer (BC) it is highly prevalent in the world with a significant mortality rate despite advances in systemic therapies. Obesity increases the risk of this cancer specially in post-menopause women and may even affect the prognosis at all ages. Objective To evaluate the impact of BMI on overall (OS) and disease free interval (DFI) of Brazilian women with BC undergoing NACT and who achieved pCR. Methods This is a retrospective study that included patients with confirmed breast cancer clinical stage I to III, age more than 18 years old and complete records that were submitted to NACT. These patients were divided in four groups based on their BMI by the World Health Organization definition BMI < 18,5 kg/m2: underweight; BMI 18,5 to < 25 kg/m2: healthy weight; BMI 25 a < 30 kg/m2: overweight; BMI ≥30kg/m2: obesity. pCR was defined as absent of invasive tumor in the breast or axilla. Student t test or chi-square test were used to analyze the association of each variable between groups with and without pCR. Univariate and multivariate analyzes were used to calculate odds ratios (OR) and 95% of confidence intervals (CI) of the independent variables BMI, age, clinical stage, immunohistochemistry and correlated with pCR (p value < 0.05 was assumed as statistically significant). The study was approved by local ethics committee. Results A total of 1.481 patients from a single reference center between January 2011 to May 2020 were included. The mean age was 50 years and mean BMI was 28,08 (SD 5,59). Most of the patients presented clinical stage III (67,3%) at diagnosis. Invasive carcinoma nonspecial type was the most frequent (95,11%). After NACT 1.138 (76.84%) still had invasive disease and only 343 (23.16%) had pCR. BMI ratio was 1.6% underweight, 30.5% healthy weight, 34.9% overweight and 33.0% obese. Regarding survival analyses, there was no statistical significance for the different BMI categories for both OS (p=0.43) and DFS (p=0.7) and no statistical significance when evaluated pCR and BMI OS (p=0.26) and DFS (p=0.22). OS was estimated for three groups (healthy weigh: 109 months, overweight: 105 months, obese: 79 months). For patients with underweight, the median OS was not reached. The 5-year OS rate in Brazil, according to this study, was 85.4%. Of these 1,481 women, 387 relapsed after surgery (22 cases: local relapse; 355: systemic relapse; 10: both relapses). Only the underweight reached the median (58 months) but this group is very small, and the other categories still have immature data because the median was not reached to define DFS. The association of the most aggressive subtypes of cancer as predictors of pCR was statistically significant (Luminal B: p=0.019; HER 2: p< 0.001; Triple negative: p< 0.001, in relation to Luminal A). There wasn’t any statistical significance for the different BMI categories. Conclusion This study did not show interference of BMI on OS and/or DFS in Brazilian women with BC undergoing NAC. Few patients reached pCR (23.16%) probably due to the advanced initial stage. On the other hand, pCR was much more frequent in the more aggressive subtypes (Triple negative, HER 2 and Luminal B). Obesity as an independent chronic condition and despite not having an impact on survival in these analyses, most women were overweight or obese (72.85%), showing the frequency of obesity in Brazilian women, which should be understood as a public health problem in the country. In addition, following these women for 10 years can help to understand better the real impact of obesity in breast cancer survival. Table 1. Percentual of breast cancer in different clinical stages. Table 2. Logistic regression considering pCR as an outcome. Citation Format: FERNANDA GRACE BAUk RICHTER, ANDRE MATTAR, Marcelo Antonini, REGINALDO G. COELHO LOPES, Jorge Y. Shida, Luis Henrique Gebrim, Juliana Monte Real. IMPACT OF THE BODY MASS INDEX (BMI) ON THE SURVIVAL OF BREAST CANCER WOMEN WHO ACHIEVED A COMPLETE PATHOLOGICAL RESPONSE (pCR) AFTER NEOADJUVANT CHEMOTHERAPY (NACT) IN BRAZIL [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-05-53.

The clinical association between breast cancer molecular subtype and clinical stage with breast density

Aim: Breast cancer is the most common malignancy in women, and dense breast tissue is a risk factor for breast cancer. However, it remains unclear whether there is an association between the breast density and molecular subtypes and clinical stage of breast cancer patients diagnosed with invasive breast cancer. We performed a retrospective cohort study to determine the association between molecular subtype and TNM clinical stage with breast density Materials and Methods: The data of female breast cancer patients who underwent treatment in our general surgery clinic between January 2019–April 2021 participated in the study. Patients’ gender, mammographic density, mammographic BI-RADS category, tumor location, TNM clinical stage, and breast cancer molecular subtypes were noted. Descriptive statistics and inferential statistics as cross-tabulations and chi-square tests were used, where applicable. Results: 230 female patients participated in the study. The mean age of the patients was 56.8 (29–88) years old. The most frequent mammographic breast density was category C (39.4%), followed by category B (33.3%). Furthermore, the most frequent mammographic BI-RADS category was category 4 (38.1%), followed by category 5 (37.2%). There was no statistically significant relationship between mammographic density and the TNM clinical stage of the patients (p=0.247). There was no statistically significant relationship between the mammographic density and molecular subtype (p=0.397). Conclusion: Mammographic breast density was not linked with the subtype or clinical stage of breast cancer. The focus of breast cancer clinical trials should be early detection, particularly in cases with dense breast tissue, regardless of molecular subtype.

CD103+ Cells and Chemokine Receptor Expression in Breast Cancer.

Mucosal environments harbour lymphocytes, which express several adhesion molecules, including intestinal homing receptors and integrin αE/β7 (CD103). CD103 binds E-cadherin, an integrin receptor expressed in intestinal endothelial cells. Its expression not only enables homing or retention of T lymphocytes at these sites but is also associated with increased T lymphocyte activation. However, it is not yet clear how CD103 expression is related to the clinical staging of breast cancer, which is determined by factors such as the size of the tumor (T), the involvement of nearby lymph nodes (N), and presence of metastasis (M). We examined the prognostic significance of CD103 by FACS in 53 breast cancer patients and 46 healthy controls enrolled, and investigated its expression, which contributes to lymphocyte recruitment in tumor tissue. Patients with breast cancer showed increased frequencies of CD103+, CD4+CD103+, and CD8+CD103+ cells compared to controls. CD103 was expressed at a high level on the surfaces of tumor-infiltrating lymphocytes in patients with breast cancer. Its expression in peripheral blood was not correlated with clinical TNM stage. To determine the localisation of CD103+ cells in breast tissue, tissue sections of breast tumors were stained for CD103. In tissue sections of breast tumors stained for CD103, its expression in T lymphocytes was higher compared to normal breast tissue. In addition, CD103+ cells expressed higher levels of receptors for inflammatory chemokines, compared to CD103- cells. CD103+ cells in peripheral blood and tumor tissue might be an important source of tumor-infiltrating lymphocyte trafficking, homing, and retention in cancer patients.

Evaluation of sister chromatid exchange in patients with breast cancer in relation to clinical stage

High levels of sister chromtid exchanges (SCE) in patients with breast caner reflects a genomic instability that may be operative in carcinogenesis.The frequency of sister chromatid exchanges in peripheral blood lymphocytes was analyzed in patients with breast cancer in relation to clinical stage in 12 stage II and 5 Stage IV untreated breast cancer patients.Moreover,SCE baseline values in patients were compared with a control group of 12 healthy women. A significant difference emerged between patients and control (P<0.01).SCE increased significantly in stage IV breast cancer patients compared with those patients of stage II (P<0.05).The results reveal that SCE frequency increases with the progression of clinical stage of breast cancer.

Novel lncRNAs with diagnostic or prognostic value screened out from breast cancer via bioinformatics analyses.

BackgroundRecent studies have shown that long non-coding RNAs (lncRNAs) may play key regulatory roles in many malignant tumors. This study investigated the use of novel lncRNA biomarkers in the diagnosis and prognosis of breast cancer.Materials and MethodsThe database subsets of The Cancer Genome Atlas (TCGA) by RNA-seq for comparing analysis of tissue samples between breast cancer and normal control groups were downloaded. Additionally, anticoagulant peripheral blood samples were collected and used in this cohort study. The extracellular vesicles (EVs) from the plasma were extracted and sequenced, then analyzed to determine the expressive profiles of the lncRNAs, and the cancer-related differentially expressed lncRNAs were screened out. The expressive profiles and associated downstream-mRNAs were assessed using bioinformatics (such as weighted correlation network analysis (WGCNA), Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) enrichments, Receiver-Operating Characteristic (ROC) curve and survival analysis, etc.) to investigate the diagnostic and prognostic values of these EV lncRNAs and their effectors.ResultsIn this study, 41 breast cancer-related lncRNAs were screen out from two datasets of tissue and fresh collected plasma samples of breast cancer via the transcriptomic and bioinformatics techniques. A total of 19 gene modules were identified with WGCNA analysis, of which five modules were significantly correlated with the clinical stage of breast cancer, including 28 lncRNA candidates. The ROC curves of these lncRNAs revealed that the area under the curve (AUC) of all candidates were great than 70%. However, eight lncRNAs had an AUC >70%, indicating that the combined one has a good diagnostic value. In addition, the results of survival analysis suggested that two lncRNAs with low expressive levels may indicate the poor prognosis of breast cancer. By tissue sample verification, C15orf54, AL157935.1, LINC01117, and SNHG3 were determined to have good diagnostic ability in breast cancer lesions, however, there was no significant difference in the plasma EVs of patients. Moreover, survival analysis data also showed that AL355974.2 may serve as an independent prognostic factor and as a protective factor.ConclusionA total of five lncRNAs found in this study could be developed as biomarkers for breast cancer patients, including four diagnostic markers (C15orf54, AL157935.1, LINC01117, and SNHG3) and a potential prognostic marker (AL355974.2).

Stage at Diagnosis and Patient Delay among Breast Cancer Women in Kabul, Afghanistan

Background: Breast cancer is the commonest cause of mortality among women. According to WHO in 2012, about 7400 women died because of cancers in Afghanistan. Aim: To obtain information about clinical stages of breast cancer of women at the time of diagnosis in Kabul, Afghanistan. Patient and Method: This was a cross-sectional study of 240 women diagnosed with breast cancer from March 2016 to March 2019. The diagnosis of breast cancer was made by the surgeon on the basis of physical examination and Biopsy/Pathological reports. Clinical staging of the tumor was recorded according to the tumor, nodal, and metastasis (TNM) classification. The gap between knowing the problem and consulting a physician (Patient delay) was categorized: less than 3 months, 3-6 months and more than 6 months. Results: The mean age of patients was 49.31 years (SD ± 11.80) ranging from 18 to 76 years. The Patient delay was more than 6 months (65%). Infiltrating ductal carcinoma was the commonest morphological type (76.7%). Breast cancer in left breast of patients was 52.1%. Stage II was higher in left and stage III in right breast. The majority of patients were in stage II & III at the time of diagnosis. All stages were frequent in fourth decades of age group. The association between the clinical stages of breast cancer at the time of diagnosis, the age and breast R/L involvement of the patients was significant (P<0.001). The association between clinical stage and marital status was not significant (P<0.953). Conclusion: Late referrals, diagnosis delay and advanced stages of breast cancer are still a serious problem in Afghanistan. Cancer in right breast should be given more attention because higher stages of the disease are expected. Awareness and social education is great need.

Impact of the COVID-19 Pandemic on Breast Cancer Screening and Operative Treatment.

IntroductionThe COVID-19 pandemic has impacted many areas of health care and had a significant impact on care delivery, including breast cancer.MethodsTo better understand the changes to detection and treatment of breast cancer at our institution, we analyzed mammogram rates (screening and diagnostic) and breast cancer operations in 2019-2020. Mammography rates were calculated using county level census data for eligible women (Z-test). For breast cancer staging, a stage severity score was analyzed with a Mann-Whitney U-test (two-tail, P < .05) with proportions derived from WFBH operative volume quarterly reports. Results: Data revealed a relative decline from 2019 to 2020 in breast cancer screening. Screening mammograms decreased by 44% or 1558 fewer screening mammograms (Z = 4.75, P < .00001) and by 21% or 771 fewer for diagnostic mammograms (Z = 2.16, P = .03). With regards to breast cancer operations, we did not identify a statistically significant difference in number of new breast cancer operations at WFBH with 340 cases in 2020 as compared to 384 cases in 2019 (P = .9905). We compared a breast cancer severity score (weighted by stage at time of operation), which did not reveal statistically significant difference in clinical stage of breast cancer at time of operation (P = .71, U = 28).ConclusionMammography was impacted more than breast surgery cases by the COVID-19 pandemic. More data needs to be collected to evaluate future morbidity and mortality related to breast cancer operations and persistent disparities related to delay in breast cancer care due to COVID-19.

Landscape Analysis of Matrix Metalloproteinases Unveils Key Prognostic Markers for Patients With Breast Cancer.

Breast cancer (BRCA) is the most common cancer in the world, of which incidence rate and mortality are the highest in women. Being responsible for the remodeling and degradation of extracellular matrix proteins, matrix metalloproteinases (MMPs) have been regarded as one of the most important protease family related to tumorigenesis. It has been demonstrated that MMPs play crucial roles in some tumor invasion and metastasis. However, the potential roles of MMPs in tumorigenesis and progression of BRCA and its subtype remain elusive. Herein, we conducted a systematic study on MMPs via a series of database-based retrospective analysis, including TCGA, R Studio, GEPIA, Kaplan-Meier Plotter, cBioPortal, STRING, GeneMANIA and TIMER. As a result, many MMP family members were differentially expressed in patients with BRCA, e.g., the expressions of MMP1, MMP9, MMP11 and MMP13 were up-regulated, whereas the expression levels of MMP19 and MMP28 were down-regulated. MMP9, MMP12, MMP15 and MMP27 were significantly correlated with the clinical stages of BRCA, implying their important roles in the occurrence and development of BRCA. In addition, the survival analysis indicated that different expression pattern of MMPs exhibited distinct outcomes in patient with BRCA, e.g., patients with high expression of MMP2, MMP8, MMP16, MMP17, MMP19, MMP20, MMP21, MMP24, MMP25, MMP26 and MMP27 had a prolonged survival time, while the others (MMP1, MMP7, MMP9, MMP12 and MMP15) exhibited poor prognosis. Subsequent functional and network analysis revealed MMPs were mainly correlated with parathyroid hormone synthesis and secretion pathway, collagen metabolism, and their effect on the activities of serine hydrolase, serine peptidase and aminopeptidase. Notably, our analysis showed that the expression of MMPs was significantly correlated with the infiltration of various immune cells in BRCA, including CD8+T cells, CD4+T cells, macrophages, neutrophils, B cells, and dendritic cells, suggesting the close correlations between MMPs and immune functions. In short, our study disclosed MMPs play multiple biological roles in the development of BRCA, MMP1 and MMP9 might be used as independent prognostic markers and potential therapeutic targets for diagnosis and treatment for patients with BRCA.

Clinical advances in PET-MRI for breast cancer.

Imaging is paramount for the early detection and clinical staging of breast cancer, as well as to inform management decisions and direct therapy. PET-MRI is a quantitative hybrid imaging technology that combines metabolic and functional PET data with anatomical detail and functional perfusion information from MRI. The clinical applicability of PET-MRI for breast cancer is an active area of research. In this Review, we discuss the rationale and summarise the clinical evidence for the use of PET-MRI in the diagnosis, staging, prognosis, tumour phenotyping, and assessment of treatment response in breast cancer. The continued development and approval of targeted radiopharmaceuticals, together with radiomics and automated analysis tools, will further expand the opportunity for PET-MRI to provide added value for breast cancer imaging and patient care.

The risk of reconstruction failure following a mastectomy, breast reconstruction and radiotherapy depending on the reconstruction technique

Improvements in the recently observed breast reconstruction surgery techniques have changed the clinical practice in patients with breast cancer. Nowadays, every patient diagnosed with breast cancer clinical stage I, II and III, except for inflammatory breast cancer, should have the opportunity to undergo breast reconstruction. Radiation therapy increases the risk of complications following reconstruction. The aim of this paper is to review the current literature in an attempt to select the safest and most convenient reconstruction technique in patients requiring radiation therapy. Immediate autologous breast reconstruction seems to be the best option, but everyday clinical practice seems to contradict the conclusions from these data. The choice of the reconstruction type depends not only on the rate of complications but on the surgeon’s skills, the patient’s preference and the hospital’s equipment.

Analysis of Adjuvant Chemotherapy on Pathological Remission of Breast Cancer.

With the continuous development of the concept of diagnosis and treatment, the current industry's treatment model has developed into a multidisciplinary comprehensive treatment. That is, in view of the pathological characteristics and clinical stages of breast cancer, corresponding methods such as surgery, chemotherapy, endocrine therapy, radiotherapy, and biological targeted therapy are adopted to provide comprehensive treatment of patients with multiple disciplines. This paper combines experimental research to research and analyze the degree of pathological remission of breast cancer by adjuvant chemotherapy and combines investigation and analysis and group trials to study and explore the effect of adjuvant chemotherapy. Moreover, this paper fully considers the patient's response to neoadjuvant chemotherapy and compares the changes in tumor cell abundance before and after chemotherapy to observe the response of the patient's primary tumor to chemotherapy at a microscopic level. Therefore, this study has made a relatively objective and accurate evaluation of the chemotherapy efficacy of tumor tissues, which can provide a reference for subsequent related research.

Heterotypic clustering of circulating tumor cells and circulating cancer-associated fibroblasts facilitates breast cancer metastasis.

Cancer-associated fibroblasts (CAFs) are recruited to the tumor microenvironment (TME) and are critical drivers of breast cancer (BC) malignancy. Circulating tumor cells (CTCs) travel through hematogenous routes to establish metastases. CTCs circulate both individually and, more rarely, in clusters with other cell types. Clusters of CTCs have higher metastatic potential than single CTCs. Previously, we identified circulating CAFs (cCAFs) in patients with BC and found that while healthy donors had no CTCs or cCAFs, both were present in most Stage IV patients. cCAFs circulate individually, as cCAF-cCAF homotypic clusters, and in heterotypic clusters with CTCs. In this study, we evaluate CTCs, cCAFs, and heterotypic cCAF-CTC clusters in patients with stage I-IV BC. We evaluate the association of heterotypic clusters with BC disease progression and metastasis in a spontaneous mouse model. Using previously established primary BC and CAF cell lines, we examine the metastatic propensity of heterotypic cCAF-CTC clusters in orthotopic and tail vein xenograft mouse models of BC. Using an in vitro clustering assay, we determine factors that may be involved in clustering between CAF and BC cells. We report that the dissemination of CTCs, cCAFs, and clusters is an early event in BC progression, and we find these clusters in all clinical stages of BC. Furthermore, cCAFs-CTC heterotypic clusters have a higher metastatic potential than homotypic CTC clusters in vivo. We also demonstrate that the adhesion and stemness marker CD44, found on a subset of CTCs and CAF cells, is involved in heterotypic clustering of these cells. We identify a novel subset of circulating tumor cell clusters that are enriched with stromal CAF cells in BC patient blood and preclinical mouse models of BC metastasis. Our data suggest that clustering of CTCs with cCAFs augments their metastatic potential and that CD44 might be an important mediator of heterotypic clustering of cCAFs and BC cells.

Detection significance of miR-3662, miR-146a, and miR-1290 in serum exosomes of breast cancer patients.

The potential relationship between exosomal microRNAs (miRNAs) and clinical symptoms in breast cancer patients and the expression levels of exosomal miRNAs in patients undergoing surgery and chemotherapy are still unclear. The aim of this study was to explore the correlation among exosomal miRNAs and clinical features and treatment in breast cancer patients. First, exosomes were isolated from the serum of patients with breast cancer and healthy controls. Next, the features of exosomes were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot assays. Then, we detected the expression of the top-ranked miRNAs (miR-3662, miR-16-1, miR-146a, miR-1290, and miR-29c) in sixty breast cancer patients and twenty healthy controls using quantitative real-time polymerase chain reaction. The differential expression was measured by the Mann-Whitney U-test. The relative expression of miR-3662, miR-146a, and miR-1290 in serum exosomes was significantly higher in patients than healthy controls. Moreover, significant differences were found in the lymph node metastasis and clinical stage of breast cancer as the miRNA levels changed, but their expression levels in exosomes and sera were not correlated. In addition, exosomal miR-3662, miR-146a, and miR-1290 were shown to be valuable biomarkers to monitor patient condition in the course of surgery and chemotherapy. Exosomal miR-3662, miR-146a, and miR-1290 may have promising predictive value and could be utilized as biomarkers for diagnosis and preventative strategy development.

Breast cancer staging in population-based registries: an alert to the quality of information

Objective: To discuss the practical difficulties associated with breast cancer staging, especially in the context of population-based cancer registries (PBCR). Methods: This is a short communication that discusses the importance and temporal evolution of breast cancer staging, as well as the limitations and new challenges associated with this process. Results: This study discusses the importance and temporal evolution of breast cancer staging, as well as the limitations and new challenges associated with this process. Minimal divergences in physical examination and disagreements in imaging tests can classify the patient in a higher or lower stage of the disease. In some population-based registries, up to 20% of the information regarding the clinical stage of breast cancer may be mistaken. Conclusion: We highlight the necessity for continuing education and constant training for all professionals involved in the breast cancer epidemiological context. The utilization of new technologies can help standardize the information and reduce the divergences related to cancer staging registry.

Germline Genetic Association between Stromal Interaction Molecule 1 (STIM1) and Clinical Outcomes in Breast Cancer Patients.

Among all cancers in women, breast cancer has the highest incidence. The mortality of breast cancer is highly associated with metastasis. Migration and malignant transformation of cancer cells have been reported to be modulated by store-operated calcium (SOC) channels, which control calcium signaling and cell proliferation pathways. Stromal interaction molecule 1 (STIM1) is a calcium sensor in the endoplasmic reticulum, triggering the activation of store-operated calcium signaling. However, the clinical relevance of STIM1 in breast cancer is still unclear. Here, we recruited 348 breast cancer patients and conducted a genetic association study to address this question. Four tagging germline single nucleotide variants (SNVs) in STIM1 were selected and RNA sequencing data of 525 breast cancer samples from The Cancer Genome Atlas (TCGA) database were evaluated. The results show that rs2304891 and rs3750996 were correlated with clinical stage of breast cancer. Expression quantitative trait loci (eQTL) analysis indicated that risk G allele of STIM1 contributed to the higher expression of STIM1. In addition, we found an increased risk of rs2304891 G allele and rs3750996 A allele in estrogen receptor (ER) positive and progesterone receptor (PR) positive patients. In conclusion, our results suggest that germline SNV, rs2304891 and rs3750996 as well as STIM1 expression are important biomarkers for the prediction of clinical outcomes in breast cancer patients.

Expression of TRPC1 and SBEM protein in breast cancer tissue and its relationship with clinicopathological features and prognosis of patients.

This study investigated the relationship of the expression of transient receptor potential channel 1 (TRPC1), small breast epithelial mucin (SBEM) in breast cancer tissues with clinical pathological features and prognosis of patients. Altogether 50 patients with breast cancer who were treated in Weifang People's hospital from April 2017 to November 2018 were selected, and the mRNA and protein differences of TRPC1 and SBEM in breast cancer patients and normal breast cancer tissues were detected by qRT-PCR and Western blot. Spearman test was used for correlation analysis. Logistic univariate and multivariate analysis were performed on the risk factors related to breast cancer metastasis in breast cancer patients. The expression of TRPC1 and SBEM in breast cancer tissues was significantly higher than that in normal breast tissues (P<0.001). The mRNA expression of TRPC1, SBEM and protein was not related to age, tumor size and tissue grade of breast cancer patients, but related to TNM stage, clinical stage and lymph node metastasis (P<0.001). The relative expression of TRPC1 was positively correlated with clinical stage of breast cancer (r=0.992, P<0.001). The relative expression of SBEM was positively correlated with the clinical stage of breast cancer (r=0.853, P<0.001). The relative expression of TRPC1 was positively correlated with TNM staging of breast cancer (r=0.860, P<0.001). The relative expression of SBEM was positively correlated with TNM staging of breast cancer (r=0.880, P<0.001). Multivariate conditional Logistic regression analysis showed that TNM staging, TRPC1, SBEM were independent risk factors for malignant breast cancer metastasis. On the contrary, expression of TRPC1 and SBEM in breast cancer tissues was up-regulated. TRPC1 and SBEM may be involved in the process of breast cancer occurrence, development and metastasis, and can be used as potential tissue biomarkers in diagnosis of breast cancer metastasis and disease assessment.

Upregulation of CCT-3 Induces Breast Cancer Cell Proliferation Through miR-223 Competition and Wnt/β-Catenin Signaling Pathway Activation.

The clinical significance and the function of chaperonin-containing TCP1 complex 3 (CCT-3) in breast cancer remain unknown. In this study, we found that CCT-3 was markedly overexpressed in breast cancer tissues. Statistical analysis revealed a significant correlation of CCT-3 expression with advanced breast cancer clinical stage and poorer survival. Ablation of CCT-3 knocked down the proliferation and the tumorigenicity of breast cancer cells in vitro and in vivo. CCT-3 may regulate breast cancer cell proliferation through a ceRNA network between miR-223 and β-catenin, thus affecting Wnt/β-catenin signaling pathway activation. We also validated that CCT-3 and β-catenin are novel direct targets of tumor suppressor miR-223. Our results suggest that both mRNA and the protein levels of CCT-3 are potential diagnosis biomarkers and therapeutic targets for breast cancer.