Clinicopathological Features Of Breast Cancer Research Articles

Association between γδ T cells and clinicopathological features of breast cancer

BackgroundThe roles of γδ T cells in patients with breast cancer (BC) have not been fully clarified, although the efficacy of gamma delta (γδ) T cells, which combine both innate and adaptive potential have extraordinary properties, such as recognizing tumor cells without the need for major histocompatibility complex (MHC) antigen presentation, as well as killing a broad range of tumor cells through their strong cytotoxic and pro-inflammatory activity, has been suggested in the majority of patients with some certain cancers. PurposeTo understand and dissect the association between γδ T cells and the clinical pathology of BC by measuring and analyzing the γδ T cell populations in the patients with BC. MethodsOn the one hand, γδ T cells were measured and analyzed by extracting from peripheral blood mononuclear cells (PBMC) of patients with BC. On the other hand, γδ T cells were measured and analyzed by performing enzymatic digestion in primary BC tissues, cancer adjacent tissues, and distant normal breast tissues from patients with different stages of cancer progression. In addition, patients with breast benign tumors and healthy volunteers were also collected as controls for this study. ResultsThe proportion of γδ T cells in PBMC was significantly correlated with tumor histological grade, ER status, the proportional value of Ki-67, and lymph node (LN) metastasis. The decrease and exhaustion of γδ T cells were a general feature in the PBMC of BC patients. In addition, the primary BC tissue infiltration of γδ T cells was significantly associated with tumor histological grade, ER status, the proportional value of Ki-67, and LN metastasis. ConclusionThese findings suggest that γδ T cell populations are crucial for understanding the clinicopathological features of patients with BC, and may serve as a valuable and independent biomarker, as well as a potential therapeutic target for human BC.

High GNG13 expression is associated with poor survival in epithelial ovarian cancer and breast cancer.

Recently, change in the GNG13 expression has been shown to result in multiple congenital malformations and sexual reversal, and it was also found in the brain. The aim of this study was to measure the expression levels in epithelial ovarian cancer (EOC) and breast cancer (BC) and assess their value as a potential prognostic marker. The correlation of GNG13 protein expression was detected by immunohistochemistry (IHC) in 119 EOC and 125 BC tissues. Assessment of the associations between GNG13 levels and various clinicopathological features was identified, the relationship between GNG13 and prognosis in BC and EOC patients was analyzed using online resources of Oncomine and Kaplan-Meier plotter. Protein expression levels of GNG13 were both significantly lower in BC and EOC compared with normal tissues (p<0.0001 and p<0.001, respectively). Among the clinicopathological characteristics of BC, tumor grade (p=0.001) and TNM stage (p=0.001) were significantly associated with low expression of GNG13. While in EOC, low expression of GNG13 was significantly related to FIGO stage (p=0.001), presence of metastasis (p=0.001), and CA125 (p=0.001). Our data suggest that GNG13 expression maybe as a new inhibitor, which can strongly inhibit metastasis and partially attenuates tumor growth in EOC and BC.

Changing Patterns in Clinicopathological Characteristics of Breast Cancer and Prevalence of BRCA Mutations: Analysis in a Rural Area of Southern China.

PurposeAlthough the burden of breast cancer remains especially high in rural China, data on the clinicopathological characteristics and prevalence of the breast cancer susceptibility gene 1/2 (BRCA1/2) mutations in patients with breast cancer remain limited. We investigated the clinicopathological characteristics, changing patterns, and prevalence of BRCA1/2 mutations in patients with breast cancer.Patients and MethodsThe clinicopathological characteristics of 3712 women with pathologically confirmed primary breast cancer treated at Meizhou People’s Hospital between January 2005 and December 2018 were evaluated. The prevalence of BRCA1/2 mutations in 340 patients with breast cancer diagnosed between January 2017 and September 2018 was also evaluated.ResultsThe median age at diagnosis was 49±10.5 (range, 20–94) years. Positivity for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) was observed in 59.0%, 52.5%, and 24.9% of patients, respectively. Time trend analysis revealed that an increasing trend was observed for age at diagnosis (p = 0.001), proportion of patients without a reproductive history (p < 0.001), postmenopausal patients (p = 0.001), invasive pathological cancer type (p = 0.008), ER-positive rate (p < 0.001), PR-positive rate (p = 0.008), and HER2-positive rate (p < 0.001). Compared with patients without BRCA1/2 mutations, those with BRCA1/2 mutations were more likely to have a family history of breast or ovarian cancer (p < 0.001) and have triple-negative breast cancer (TNBC) (p < 0.001). Family history of breast or ovarian cancer (odds ratio [OR], 103.58; 95% confidence interval [CI], 20.58–521.45; p < 0.001) and TNBC subtype (OR, 5.97; 95% CI, 1.16–30.90; p = 0.033) were independent predictors for BRCA1/2 mutation.ConclusionThe clinicopathological characteristics of patients with breast cancer in this rural area have changed during the past decade. BRCA1/2 testing should be performed in patients with breast cancer with a family history of breast or ovarian cancer and TNBC.

Association of Preoperative Serum Levels of CEA and CA15-3 with Molecular Subtypes of Breast Cancer

Objectives Molecular subtypes are employed as a guide for targeted treatment and important prognostic factors. This study focused on investigating the association of serum levels of CEA, CA15-3, and CA125 with clinicopathological characteristics of breast cancer to find prognostic markers for breast cancer and provide precise targeted therapy. Materials and Methods In this study, 961 breast cancer patients with preoperative serum levels of CEA, CA15-3, and CA125 and molecular subtypes were analyzed. Cut-off values of 5 ng/ml, 25 U/ml, and 35 U/ml were used for CEA, CA15-3, and CA125, respectively. The χ2 test and Fisher exact test along with logistic multivariate regression analysis were performed for investigating the correlation of CEA, CA15-3, and CA125 serum levels with molecular subtypes and associated factors. Results An increase in the serum concentrations of CEA, CA15-3, and CA125 was discovered in 48 (4.99%), 54 (5.62%), and 55 (5.72%) breast cancer patients, respectively. Univariate analysis demonstrated that the levels of CEA (p < 0.01) and CA15-3 (p < 0.05) were significantly linked with molecular types of breast cancer. Moreover, patients having larger tumor size (p < 0.01, p < 0.0001, and p < 0.05, respectively) along with nodal metastasis (p < 0.05, p = 0.0001, and p < 0.05, respectively) exhibited higher rates of elevated CEA, CA15-3, and CA125 levels. Status of Her-2 positive (p < 0.01) had a significant connection with elevated CEA levels. Multivariate analysis further indicated that molecular subtypes were independent factors associated with CEA and CA15-3 levels. Also, Her-2 status was significantly and independently related to CEA levels. Conclusion Preoperative serum levels of CEA and CA15-3 were independently associated with molecular subtypes of breast cancer. CEA and CA15-3 might improve the prognostic prediction for patients with breast cancer and inform the selection of specific therapies. A further biological analysis is needed for investigating the relationship between Her-2 expression and CEA levels.

Significant difference between coagulation parameters and clinicopathological characteristics in breast cancer.

The purpose of this research is to investigate the correlation between coagulation parameters and survival on patients with breast cancer. A total of 244 patients with breast cancer and 84 patients with metastatic advanced breast cancer admitted to the Second Affiliated Hospital of Chongqing Medical University from January 2017 to February 2019 were selected as the research objects. Their age, tumor size, status of estrogen receptor and progesterone receptor status, status of Her-2 receptor and lymph node were evaluated. Additional 99 cases of benign breast tumors were selected as the control group. All patients were newly diagnosed. PTA, PT ratio, PT, APTT, APTT ratio, TT, TT ratio, PT-INR, FIB, and FDP were detected on all patients. There were significant differences in APTT, APTT ratio, FIB, TT, TT ratio, and FDP between breast cancer and benign tumor control group (P < 0.05). The changes of FIB were correlated with age (P = 0.007), PR status (P = 0.017), and Her-2 status (P = 0.008). The older the age, the higher the FIB level. The FIB level of Er negative state is higher than that of positive state, and the FIB level of PR negative state is also higher than that of positive state. Survival analysis showed that PR negative status, the elevated level of APTT, APTT ratio, TT increased, and TT ratio were the indicators affecting 3-year DFS of patients (P < 0.05). Multivariate COX regression analysis showed that APTT and TT were independent prognostic factors affecting 3 years DFS (P < 0.05). Blood hypercoagulable state in patients with breast cancer, abnormal coagulation system plays an important role in the progress of breast cancer.

PPA1 Promotes Breast Cancer Proliferation and Metastasis Through PI3K/AKT/GSK3β Signaling Pathway.

Breast cancer is the most common malignancy among women. Inorganic pyrophosphatase 1 (PPA1) is a multifunctional protein involved in the development of several tumors. However, the role of PPA1 in breast cancer progression remains unclear. In this study, we found that PPA1 was highly expressed in breast cancer compared to its levels in normal breast tissue and that it was correlated with breast cancer clinicopathological characteristics, as well as poor survival in breast cancer patients. Silencing PPA1 restrained breast cancer proliferation and metastasis by regulating Slug-mediated epithelial-mesenchymal transition (EMT). Opposite results were observed following PPA1 overexpression. In addition, investigation of the underlying mechanism demonstrated that PPA1 ablation led to decrease phosphatidylinositol 3 kinase (PI3K) phosphorylation levels and attenuate phosphorylated AKT and glycogen synthase kinase-3 β (GSK3β), while ectopic PPA1 expression had the opposite effects. Moreover, PI3K inhibitors suppress the signaling pathways mediating the effects of PPA1 on breast cancer, resulting in tumor growth and metastasis suppression in vitro and in vivo. In summary, our results verify that PPA1 can act as an activator of PI3K/AKT/GSK3β/Slug-mediated breast cancer progression and that it is a potential therapeutic target for the inhibition of tumor progression.

Prognostic value of tumor-infiltrating lymphocytes (TILS) and their association with clinicopathological features in breast cancer: A retrospective study involving 53 cases

ObjectiveQuantitative analysis of tumor-infiltrating lymphocytes (TILs) is currently considered as a prognostic factor in several malignant tumors. The aim of our study was to assess the prognostic value of TILs in breast cancers and its association with other clinicopathological prognostic factors in non-specific type (NST) breast carcinoma in Tunisian population. MethodsRetrospective study included 53 women with NST breast carcinoma. The data were collected over a period of 13 months with a follow-up of 40 months for all the patients. The TILs were evaluated according to the 2014 recommendations of the international working group on TILs. ResultsTILs level was between 3% and 60% with mean of 21%. Ten patients had lymphocyte predominant breast cancer (LPBC). Statistical analysis had shown that the TILs level ≤50% was associated with the presence of vascular emboli and the absence of HER2 amplification. Inflammatory-type carcinoma and HER2 amplification significantly worsened OS. Presence of vascular emboli, lymph node metastases, inflammatory type of carcinoma, TILs ≤50%, and absence of estrogen receptors (ER) were associated with reduced RFS. In multivariate analysis, the presence of vascular emboli was an independent factor for OS. TILs ≤50%, inflammatory type of carcinoma and presence of vascular emboli were independent risk factors for RFS. ConclusionThis Tunisian pilot study showed higher level of TILs in NST breast carcinomas is associated with improved RFS. The therapeutic implications will benefit from multiple research studies including ours on the predictive value of TILs for neoadjuvant or adjuvant treatment.

LRP6 as a biomarker of poor prognosis of breast cancer.

Recently, low-density lipoprotein receptor (LDLR)-related protein 6 (LRP6) has been the focus of molecular targeted therapy for breast cancer; however, its role in breast cancer is still controversial. The purpose of this study was to investigate the effect of LRP6 overexpression on the prognosis of breast cancer. We used immunohistochemistry to detect the expression of LRP6 via tissue microarrays in breast cancer samples, Chi-square test analyze the relationship between LRP6 expression and clinicopathological features of breast cancer, the Kaplan-Meier method to perform survival analysis, and the Cox proportional hazards regression model to explore the potential risk factors of breast cancer. The role of LRP6 in the proliferation, invasion, and metastasis of breast cancer was studied by colony formation, Transwell migration and invasion assay and scratch assay. The tumor-bearing model of LRP6 knockdown was established using MCF-7 cells, and corresponding negative control was set up to observe the growth rate of the two models. High expression of LRP6 was observed in 89 out of 150 (59.3%) breast cancer cases, as detected by microarray of breast cancer tissue. Chi-square tests showed no significant correlation between LRP6 expression and tumor size, lymph node staging, or mitosis. Survival analysis showed that the overall survival rate of tumor patients with high LRP6 expression was significantly lower than that of patients with low LRP6 expression. Univariate and multivariate regression analyses revealed that LRP6 was an independent risk factor for breast cancer and was negatively correlated with the prognosis of breast cancer. Compared with the control group, small interference RNA (si-RNA) knockdown of LRP6 significantly reduced the clonogenic rate as well as the migration and invasion abilities of MCF-7 cells. In the scratch experiment, the wound healing ability of the LRP6 knockdown was significantly weaker than that of the control group. There were significant differences in tumor growth weight and volume between lentivirus transfected LRP6 knockdown MCF-7 cell line and control MCF-7 cell line in nude mice. LRP6 could be a useful biomarker of poor prognosis of breast cancer, as it plays an important role in tumor growth, migration, and invasion.

Correlation between expression of long chain non-coding RNA00707 and clinicopathological features of breast cancer

目的： 研究长链非编码RNA00707在乳腺癌组织中的表达及其与乳腺癌临床病理特征的相关性。 方法： 建立人脂肪间充质干细胞（hAD-MSCs）与人乳腺癌MCF7细胞间接共培养体系。并诱导MCF7细胞上皮-间充质转化（EMT），通过lncRNAs芯片技术，最终获得差异表达的长链非编码RNA00707。收集民航总医院及衡道病理中心提供的2015—2019年乳腺癌组织标本136例。应用RNAscope技术检测并统计分析乳腺癌组织中Linc00707的阳性表达与肿瘤大小、组织学分级、腋窝淋巴结转移及血管内癌栓的关系。 结果： 121例阳性病例，Linc00707呈细胞核及细胞质内点簇状棕褐色颗粒。（1）Linc00707在T2、T3、T4组的阳性表达率均高于T1组。（2）Linc00707在乳腺癌组织学Ⅱ、Ⅲ级中的阳性表达率高于乳腺癌组织学Ⅰ级，差异有统计学意义（P<0.05）。（3）Linc00707在有淋巴结转移的N1、N2、N3组的阳性表达率明显高于无淋巴结转移的N0组。（4）Linc00707阳性表达率在有无血管内癌栓之间差异无统计学意义（P>0.05）。（5）Linc00707在<50岁与≥50岁之间阳性表达率差异无统计学意义（P>0.05）。 结论： Linc00707在乳腺癌中的阳性表达与肿瘤大小、组织学分级、腋窝淋巴结转移呈正相关，结果显示Linc00707能够促进乳腺癌的生长、增殖、侵袭和转移。.

Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort.

Simple SummaryBreast cancer, one of the leading causes of death among women, is a complex disease in which several factors, such as psychosocial stress, have been implicated in its initiation and progression. The glucocorticoid receptor (GCR) is one of the molecules that transfers the stress signal into the body. We measured the genetic variation and protein expression of GCR and the genes that regulate GCR function or response and examined whether these variations were associated with breast cancer. We found several genetic variants of functionally important SNPs associated with later disease stage, higher grade, and hormone receptor-negative status. The GCR protein expression was reduced in breast cancer tissue and correlated with the basal cell marker CK5/6.Background: Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (GCR/NR3C1), to regulate a myriad of physiological processes. We measured the genetic variation and protein expression of GCR, and the genes that regulate GCR function or response and examined whether these alterations were associated with breast cancer clinicopathological characteristics. Method: We used samples from a multiracial cohort of breast cancer patients to assess the association between breast cancer characteristics and the genetic variants of single nucleotide polymorphisms (SNPs) in GCR/NR3C1, FKBP5, Sgk1, IL-6, ADIPOQ, LEPR, SOD2, CAT, and BCL2. Results: Several SNPs were associated with breast cancer characteristics, but statistical significance was lost after adjustment for multiple comparisons. GCR was detected in all normal breast tissues and was predominantly located in the nuclei of the myoepithelial cell layer, whereas the luminal layer was negative for GCR. GCR expression was significantly decreased in all breast cancer tissue types, compared to nontumor tissue, but was not associated with breast cancer characteristics. We found that high nuclear GCR expression was associated with basal cell marker cytokeratin 5/6 positivity. Conclusion: GCR expression is reduced in breast cancer tissue and correlates with the basal cell marker CK5/6.

Expression and clinical significance of pyruvate kinase M2 in breast cancer: A protocol for meta-analysis and bioinformatics validation analysis.

Background:Breast cancer is a common malignant tumor in women. In recent years, its incidence is increasing year by year, and its morbidity and mortality rank the first place among female malignant tumors. Some key enzymes and intermediates in glycolysis are closely related to tumor development. Pyruvate kinase M2 (PKM2) is an important rate-limiting enzyme in glycolysis pathway. Meanwhile, it is highly expressed in proliferative cells, especially in tumor cells, and plays an important role in the formation of Warburg effect and tumorigenesis. Previous studies have explored the effects of PKM2 expression on the prognosis and clinical significance of breast cancer patients, while the results are contradictory and uncertain. This study uses controversial data for meta-analysis to accurately evaluate the problem. We collected relevant Oncomine and The Cancer Genome Atlas (TCGA) data to further verify the results. Through bioinformatics analysis, the mechanism and related pathways of PKM2 in breast cancer are explored.Methods:We searched Wanfang, Chinese Biomedical Literature Database, Chinese National Knowledge Infrastructure, the Chongqing VIP Chinese Science and Technology Periodical Database, PubMed, Embase, and Web of Science databases from inception to March 2021. The language restrictions are Chinese and English. The published literatures on PKM2 expression and prognosis or clinicopathological characteristics of breast cancer patients were statistically analyzed. Combined hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (95% CIs) were used to evaluate the effects of PKM2 on the prognosis and clinicopathological features of breast cancer. Stata 14.0 software was applied for meta-analysis. Oncomine and TCGA databases were used to meta-analyze the differences of PKM2 mRNA expression between breast cancer and normal breast tissues. The expression of PKM2 protein was verified by Human Protein Atlas (HPA) database. The relationship between the gene and the survival of breast cancer patients was analyzed by Gene Expression Profiling Interactive Analysis (GEPIA). The relationship between PKM2 gene and clinicopathological characteristics was analyzed by using LinkedOmics, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis was performed by using Metascape. Protein–protein interaction (PPI) network was constructed by String website.Results:The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.Conclusion:This study provides high-quality medical evidence for the correlation between the expression of PKM2 and the prognosis and clinicopathological features of breast cancer. Through bioinformatics analysis, this study further deepens the understanding of the mechanism and related pathways of PKM2 in breast cancer.Ethics and dissemination:The private information from individuals will not be published. This systematic review also should not damage participants’ rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences.OSF REGISTRATION NUMBER:DOI 10.17605/OSF.IO/W52HB.

Evaluation of the use of long noncoding RNAs as biomarkers for diagnosis of breast cancer: Thesis Abstract

Background: FAM83H antisense RNA 1 (FAM83H-AS1) and long noncoding RNA activated by TGF β (lncRNA-ATB) are two lncRNAs that have tumor promoting functions in breast cancer (BC). Matrix metalloproteinase-9 (MMP-9) is another tumor marker that exerts an oncogenic role in BC and facilitate cancer invasion and metastasis. Aims: Our study aimed to 1) analyze serum levels of FAM83H-AS1, lncRNA-ATB, and MMP-9 in BC patients, 2) compare their diagnostic role with that of CA15-3 in BC patients with different stages (I-II, III, and IV), and 3) correlate the levels of the measured lncRNAs, MMP-9, and CA15-3 with the clinicopathological features of BC. Materials and Methods: Serum FAM83H-AS1 and lncRNA-ATB levels were analyzed in 90 BC patients and 30 healthy controls using RT-PCR. While serum levels of MMP-9 and CA15-3 were measured in the same studied groups by ELISA. Results: FAM83H-AS1, lncRNA-ATB, MMP-9, and CA15-3 levels were significantly elevated in sera of BC patients. ROC curve analysis showed that lncRNA-ATB and MMP-9 had higher AUC values than CA15-3 in diagnosis of stage I-II patients (AUC: 0.844 and 0.898, p= 0.000 for lncRNA-ATB and MMP-9, respectively versus 0.738, p= 0.002 for CA15-3). FAM83H-AS1 level was significantly correlated with higher stage, larger tumor size, positive lymph node metastasis, and distant metastasis. FAM83H-AS1 level was also significantly increased in PR-negative and ki67-rich tumors. Conclusion: Our study demonstrated that circulating lncRNA-ATB and MMP-9 could be used as diagnostic biomarkers for early BC. FAM83H-AS1 could also be a potential candidate for staging BC and monitoring disease progression.

The lncRNA GATA3-AS1/miR-495-3p/CENPU axis predicts poor prognosis of breast cancer via the PLK1 signaling pathway

The function of centromere protein U (CENPU) gene in breast cancer has not been well understood. Therefore, we explored the expression profiles of CENPU gene in breast carcinoma to better understand the functions of this gene, as well as the relationship between CENPU expression and the prognosis of breast carcinoma patients. Our results indicate that CENPU was expressed at significantly higher levels in cancerous tissues than in normal tissues. Furthermore, CENPU expression correlated significantly with many clinicopathological characteristics of breast cancer. In addition, we discovered that high levels of CENPU expression predicted poor prognosis in patients with breast cancer. Functional investigation revealed that 180 genes exhibited co-expression with CENPU. Functional annotation indicated that 17 of these genes were involved in the PLK1 signaling pathway, with most of them (16/17) being expressed at significantly higher levels in malignant tissues compared with normal controls and correlating with a poor prognosis. Subsequently, we found that four miRNAs, namely hsa-miR-543, hsa-miR-495-3p, hsa-miR-485-3p, and hsa-miR-337-3p, could be regarded as potential CENPU expression regulators. Then, five lncRNAs were predicted to potentially bind to the four miRNAs. Combination of the results from expression, survival, correlation analysis and functional experiments analysis demonstrated the link between lncRNA GATA3-AS1/miR-495-3p/CENPU axis and prognosis of breast cancer. In conclusion, CENPU could be involved in cell cycle progression through PLK1 signaling pathway.

The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival.

Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I-II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size (P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status (P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

Clinicopathological Features of Breast Cancer with Polysomy 17 and Its Response to Neoadjuvant Chemotherapy.

The interpretation of human epidermal growth factor receptor 2 (HER2) fluorescence in situ hybridization (FISH) results may be challenging in tumors with polysomy 17, which is defined as increased signals of chromosome enumeration probe 17 (CEP17). The effect of polysomy 17 on HER2 protein expression and tumor treatment response has not been established. In this retrospective study, we investigated the clinicopathological features of breast cancer with polysomy 17 and determined the tumors' response to neoadjuvant chemotherapy (NACT). The study included 366 patients with primary breast cancer whose tumors had a CEP17 count of ≥ three/nucleus based on HER2 FISH studies. These cases were categorized according to HER2/CEP17 ratio and HER2 signals/nucleus using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines. We compared the clinicopathological characteristics and tumor response to NACT among different groups. There was a statistically significant difference in patients' age at diagnosis, tumor pathological grade, estrogen and progesterone receptor status, and NACT response among different HER2 FISH groups. Polysomy 17 tumors in group 1 had a higher rate of response (pathological complete response and residual cancer burden class I) to NACT containing anti-HER2 reagent than did those in other groups (p = 0.004), whereas polysomy 17 tumors in group 3 did not show a significant response to anti-HER2 treatment. Polysomy 17 tumors in different HER2 FISH groups have different pathological features and respond to NACT differently. These results may help us identify patients who will benefit from anti-HER2 therapy.

KIF15 expression characteristics: Relevance toneo-adjuvant chemotherapy efficacy in breast cancer*

Abstract Objective The relationship between the expression of kinesin family member 15 (KIF15) and clinicopathological features in breast cancer (BC) remains controversial. In this study, we aimed to explore the influence of KIF15 expression on the efficacy of neoadjuvant chemotherapy (NAC) and evaluate its clinical value in predicting prognosis for BC patients. Methods Immunohistochemistry was used to detect KIF15 expression in 93 BC patients undergoing NAC to analyze the relationship between KIF15 expression and clinical efficacy and analytical parameters. Results Of the 93 BC patients enrolled, 24.73% who underwent NAC had higher KIF15 expression levels, showing positive correlations with ER, HER-2, Ki67, and lymph node metastasis (P &lt; 0.05). The clinical benefit of NAC was 70.97%, and the major histological response (MHR) rate was 61.29%. The effective therapeutic rate in patients with high KIF15 expression was 95.65%, while the MHR rate was 65.22%. Various molecular BC subtypes with varied clinical and pathological responses exhibited correlation to a large extent. Of all the BC patients studied, 84% of the triple-negative breast cancer (TNBC) patients were evaluated as clinically effective, and 52% of the TNBC patients were evaluated as pathologically effective, and these values were significantly higher than those of the other molecular types (P &lt; 0.05). The expression of KIF15 in 25 TNBC patients showed positive correlations with lymph node metastasis. Conclusion Overexpression of KIF15 was shown to increase BC sensitivity to chemotherapy and demonstrated better outcomes.

Expression and Prognosis of Sperm-Associated Antigen 1 in Human Breast Cancer

BackgroundSperm-associated antigen 1 (SPAG1) has been identified as a marker of pancreatic cancer progression and promoter of cell motility; however, its role in breast cancer is not completely understood.MethodsSPAG1 expression in breast cancer tissues and normal tissues was obtained from online databases. Knockdown function assays were designed and conducted to verify the functional role of SPAG1 in breast cancer cell lines. Cell counting and MTT assays were used to assess cell proliferation. Cell flow cytometry assay was used for cell cycle phase arrest, and fluorescence microscopy was used for colony formation assessment.ResultsBoth the mRNA and protein levels of SPAG1 were significantly higher in the breast cancer tissues than in the normal tissues. In addition, SPAG1 is significantly related to many clinicopathological features of breast cancer, such as age (>51 years), estrogen receptor (ER) (+), progesterone receptor (PR) (+), and nodal status (+), non-triple negative breast cancer (TNBC), not basal-like and not basal-like and not TNBC. Survival analysis indicates that breast cancer patients with low expression of SPAG1 had a significantly better prognosis with relapse-free survival (RFS). Functional experiment analysis revealed that knockdown of SPAG1 suppressed cell proliferation and colony-forming ability.ConclusionOur results suggested a possible role of SPAG1 in breast cancer pathogenesis.

Características clínico-patológicas de cáncer de mama en mujeres: un estudio de 1,840 diagnósticos

Objetivo: Reportar las características clínico-patológicas de mujeres diagnosticadas con cáncer de mama (Cama) que fueron atendidas en el Instituto Jalisciense de Cancerología (IJC), localizado en Guadalajara, Jalisco, durante el quinquenio 2013-2017.&#x0D; Materiales y métodos: Diseño transversal y analítico cuya fuente de datos fueron los expedientes clínicos y el registro electrónico del IJC. Se incluyeron y analizaron los siguientes datos de mujeres con diagnóstico confirmado de Cama: edad, grado y variedad histológica, estadio clínico reportado por las categorías in situ (0), temprano (I-IIA), localmente avanzado (IIB-IIIC) y metástasis (IV), así como estatus de los receptores hormonales. Las mujeres fueron clasificadas en dos grupos de edad: &lt;40 e ≥40 años, con la finalidad de comparar las características clínico-patológicas mediante pruebas estadísticas. Se presenta análisis descriptivo de los datos.&#x0D; Resultados: Se recolectaron y analizaron datos relacionados a 1,840 diagnósticos de Cama; la edad promedio de las mujeres al momento del diagnóstico fue 53.2 años. Las características clínico-patológicas de mayor frecuencia fueron: localmente avanzado (53.1%), ductal (88.9%), moderadamente diferenciado (60.1%) y Luminal A (31.6%); mientras que el 15% de los casos reportó la clasificación triple negativo, principalmente mujeres &lt;40 años (21.3%). Salvo la variedad histológica (p &lt;0.05), no se encontraron diferencias significativas entre ambos grupos de edad respecto a las características clínico-patológicas analizadas.&#x0D; Conclusiones: En México, raramente han sido reportadas las características clínico-patológicas del Cama en mujeres, cuya importancia radica en el manejo clínico y la toma de decisiones respecto a los diversos tratamientos terapéuticos. Por tanto, la evidencia aquí presentada contribuye, por un lado, a reconocer cuál es el perfil clínico-patológico de las mujeres que buscaron atención oncológica en el IJC durante el quinquenio 2013-2017 y, por otro, es útil para desarrollar otros estudios epidemiológicos que evalúen la repercusión en la recurrencia del Cama y las posibilidades de supervivencia de las mujeres.

Brown adipose tissue (BAT) activation at 18F-FDG PET/CT: correlation with clinicopathological characteristics in breast cancer

BackgroundThere is conflicting results of few published human 18F-FDG PET/CT studies about BAT activation in breast cancer (BC). The aim of the study is to evaluate the association between the levels of BAT metabolic activity detected by 18F-FDG PET/CT and clinicopathological characteristics of a tumor in patients with primary BC.ResultsBAT was activated in 16 out of 157 (10.2%) consecutive female patients with BC who underwent 18F-FDG PET/CT for initial evaluation. The majority of patients (15/16) had bilateral uptake in the supraclavicular regions. The mean values of the highest SUVmax and total metabolic activity (TMA) of activated BAT were 13.3 ± 9.9 and 79.6 ± 45, respectively. Median outdoor temperature was significantly lower in the activated BAT group (P value=0.035). Patients with BAT activation tended to have a lower median primary tumor size and primary SUVmax, but not statistically significant than those without BAT activation. BAT activation was significantly more frequent among younger age groups (14/16) and patients with lower body mass index (BMI) (10/16), but it was insignificantly more frequent among estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor2 negative (HER2-), invasive ductal carcinoma (IDC), grade II, luminal B subtype, high Ki-67 expression level, patients with positive nodal metastasis, and in patients without distant metastasis. TMA was significantly higher among HER2+ patients (P value=0.019), but insignificantly higher among the younger age groups, stages I and II, invasive lobular carcinoma (ILC), grade I, luminal B subtype, ER+, PR−, higher Ki-67 expression level, patients with positive nodal, and distant metastasis. BMI and patient’s age were the significant independent predictor factors for BAT activation on multivariate regression analysis.ConclusionBAT activation in young age females is sex hormone-dependent, positively associated with less aggressive molecular subtypes of BC, less frequent in patients with distant metastasis. BAT activation may be a prognostic factor that carries a better prognosis in BC.

Abstract OT-10-01: A study to observe patients characteristics, treatment patterns and outcomes in patients with newly diagnosed breast cancer in Latin America - LATINA breast (LACOG 0615/ MO39485)

Abstract Background: Breast cancer (BC) is the most common malignancy and one of the leading causes of cancer death in Latin American women, with an estimated age-standardized annual incidence of 38.3 and 56.8 and mortality rates of 10.1 and 13.4 cases per 100,000 females, in Central and South America respectively. However, BC incidence in Latin America (LATAM)is largely underestimated and lacks updated information. Furthermore, the shortage and quality of cancer registry data hinders a more reliable assessment of treatment and outcomes for these patients. The goals of LATINA Breast study is to build an electronic platform/database to allow a standardized collection of epidemiological data of BC in LATAMin addition to describe real world data on patients characteristics, treatment patterns and outcomes of this population. Methods: LATINA Breast (LACOG 0615) is a prospective, international, multicentre and non-interventional study of primary data collection designed to describe the diagnosis, oncologic treatment and outcomes of patients with BC in LATAM. Patients aged ≥ 18 years with stage I to IV newly diagnosed BC (i.e. &amp;lt;12 months since site activation) will be considered eligible for inclusion.Patient data will be collected from medical records at diagnosis and every 6 months for up to 5 years of follow-up. At baseline, data on socioeconomic, demographic, medical history and BC clinicopathological characteristics will be collected. Thereafter, information regarding treatment patterns, sequencing, response to treatment, adverse events, disease relapse/ progression and overall survival will be collected at each time-point. This study has a planned sample size of a minimum of 2.200 to a maximum of 4.500 patients accrued from approximately 30 sites in 10 LATAM countries: Argentina, Brazil, Cuba, Colombia, Chile, Dominican Republic, Ecuador, Mexico, Peru and Uruguay. The expected number of patients per country is based on age-standardize BC incidence rate by GLOBOCAN 2012 and not in a formal statistical estimation.Co-primary endpoints are (1) to describe patients’ characteristics, prevalence of BC subtypes at diagnosis, local and systemic treatment patterns and outcomes; (2) to build an electronic platform/database of epidemiological data of BC in LATAM. Secondary endpoints are to evaluate regional differences in treatment strategies, to describe treatment efficacy parameters such as locoregional relapse, invasive disease-free survival, progression-free survival, overall survival and to evaluate treatment safety. The trial is registered at clinicaltrials.gov NCT04158258.Results The first site was activated for patient accrual on February 13, 2020, in Argentina. As of July 6, 2020, a total of 243 patients have been included in Argentina (n=81), Brazil (n=123), Colombia (n=37), and Guatemala (n=2) within 19 active sites. Regulatory approval and activation are ongoing in the other countries. Recruitment is estimated to last until December 2021 to achieve the planned sample size. Patients will be followed-up for 5 years, therefore we estimate the last follow-up data collection in December 2026. ConclusionLATINA Breast is the first multinational, prospective cohort study of BC in Latin America that will generate detailed information on diagnosis, treatment and outcome in real-world clinical practice. It will address important gaps in BC management and will likely single out some of the main inequities in this large and diverse population of BC patients and consequently support strategies for the improvement of BC cancer care in LATAM. Citation Format: Gustavo Werutsky, Cynthia Villareal-Garza, Henry Gomez, Juan Manuel Donaire, José Bines, Luis Fein, Mariano Nicolas Carrizo, Facundo Zaffaroni, Paulo Ricardo Nunes Filho, Carlos H Barrios. A study to observe patients characteristics, treatment patterns and outcomes in patients with newly diagnosed breast cancer in Latin America - LATINA breast (LACOG 0615/ MO39485) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr OT-10-01.