Clinicopathological Features Of Breast Cancer Research Articles

Ultrasonography and clinicopathological features of breast cancer in predicting axillary lymph node metastases

BackgroundEarly identification of axillary lymph node metastasis (ALNM) in breast cancer (BC) is still a clinical difficulty. There is still no good method to replace sentinel lymph node biopsy (SLNB). The purpose of our study was to develop and validate a nomogram to predict the probability of ALNM preoperatively based on ultrasonography (US) and clinicopathological features of primary tumors.MethodsFrom September 2019 to April 2022, the preoperative US) and clinicopathological data of 1076 T1-T2 BC patients underwent surgical treatment were collected. Patients were divided into a training set (875 patients from September 2019 to October 2021) and a validation set (201 patients from November 2021 to April 2022). Patients were divided into positive and negative axillary lymph node (ALN) group according pathology of axillary surgery. Compared the US and clinicopathological features between the two groups. The risk factors for ALNM were determined using multivariate logistic regression analysis, and a nomogram was constructed. AUC and calibration were used to assess its performance.ResultsBy univariate and multivariate logistic regression analysis, age (p = 0.009), histologic grades (p = 0.000), molecular subtypes (p = 0.000), tumor location (p = 0.000), maximum diameter (p = 0.000), spiculated margin (p = 0.000) and distance from the skin (p = 0.000) were independent risk factors of ALNM. Then a nomogram was developed. The model was good discriminating with an AUC of 0.705 and 0.745 for the training and validation set, respectively. And the calibration curves demonstrated high agreement. However, in further predicting a heavy nodal disease burden (> 2 nodes), none of the variables were significant.ConclusionThis nomogram based on the US and clinicopathological data can predict the presence of ALNM good in T1-T2 BC patients. But it cannot effectively predict a heavy nodal disease burden (> 2 nodes).

Pro-Inflammatory and Anti-Inflammatory Salivary Cytokines in Breast Cancer: Relationship with Clinicopathological Characteristics of the Tumor.

The aim of the work was to compare the salivary cytokine profile of breast cancer patients with the clinicopathological characteristics of the tumor. The study included 113 patients with breast cancer (main group, mean age 54.1 years) and 111 patients with breast fibroadenomas (control group, mean age 56.7 years). Before treatment, saliva samples were collected from all patients and the content of cytokines (IL-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, MCP-1, and TNF-α) was determined. The content of cytokines in saliva correlates well with the clinicopathological characteristics of breast cancer. The level of all salivary cytokines increases at advanced stages of breast cancer and at a low degree of tumor differentiation. The exception is MCP-1, for which there is an extremely high content for well-differentiated breast cancer. A statistically significant increase in the content of MCP-1, IL-1β, IL-2, IL-4, and IL-10 was found in triple-negative breast cancer. For the first time, the correlation of salivary levels of TNF-α, IL-1β, and IL-6 with HER2 status, MCP-1, IL-1β, IL-2, and IL-4 with the hormonal status of the tumor was shown. The relationship between the level of IL-2, IL-10, and IL-18 in saliva with the level of Ki-67 expression has been established.

Association between epidemiological and clinico-pathological features of breast cancer with prognosis, family history, Ki-67 proliferation index and survival in Tunisian breast cancer patients.

Breast cancer has different epidemio-clinical characteristics in Middle East and North-African populations compared to those reported in the Western countries. The aim of this study is to analyze the epidemiological and clinico-pathological features of breast cancer in Tunisia and to determine prognostic factors with special interest to family history, Ki-67 proliferation index and comorbidity. We retrospectively reviewed epidemiological and clinico-pathological data from patients' medical records, treated in the Medical Oncology Department at Abderrahmane Mami Hospital, in the period 2011-2015. Data has been collected on 602 breast cancer patients and analyzed using SPSS software V.23.0. Our study showed high fractions of young breast cancer patients and cases with dense breasts. The most prevalent comorbidities observed in the studied cohort were cardiovascular diseases and diabetes. Familial breast cancer was found in 23.3% of cases and was associated with younger age at diagnosis (p<0.001) and advanced stage (p = 0.015). Ki-67 index >20% was significantly associated with early age at diagnosis, lymph node involvement (p = 0.002), advanced tumor grade (p<0.001) and high risk of relapse (p = 0.007). Ki-67 cut-off 30% predicted survival in luminal cases. Survival was worse in patients with triple negative breast cancer compared to non-triple negative breast cancer, inflammatory breast cancer compared to non-inflammatory breast cancer, moderately to poorly differentiated tumors compared to well-differentiated tumors and with positive lymph nodes compared to pN0 (p<0.05). Our study showed new insights into epidemiological and clinico-pathological characteristics of breast cancer that are not well explored in Tunisian population. Considering our findings along with the implementation of electronic health record system may improve patient health care quality and disease management.

Unfavorable prognosis and clinical consequences of APOBEC3B expression in breast and other cancers: A systematic review and meta-analysis.

Controversy exists regarding the association of apolipoprotein B mRNA editing enzyme catalytic subunit 3B APOBEC3B, (A3B) overexpression and poor prognosis, metastasis, and chemotherapy drug resistance in cancers. Here we conducted a systematic review and meta-analysis to determine its prognostic value and clinicopathological features in breast cancer and some other malignancies. PubMed, Scopus, Cochrane Library, Web of Science, and EMBASE were searched up to Feb 2022 for the association of A3B with breast, ovarian, gastrointestinal and lung cancers. The pooled hazard ratios with 95% confidence interval (CI) were evaluated to assess disease-free survival (DFS), overall survival (OS), and recurrence-free survival (RFS) in cancers under study. Over 3700 patients were included in this meta-survey. Elevated levels of A3B were significantly related to low OS (pooled HR = 1.30; 95% CI:1.09-1.55, P < 0.01), poor DFS (pooled HR = 1.66; 95% CI:1.17-2.35, P < 0.01) and poor RFS (HR = 1.51, 95% CI:1.11-2.04, P = 0.01). Subgroup analysis revealed that high A3B expression was associated with poor OS in lung (HR = 1.85, 95% CI: 1.40-2.45), and breast cancers (HR = 1.38, 95% CI: 1.00-1.89). High expression of A3B did not display any significant association with clinicopathologic features. APOBEC3B overexpression is related to poor OS, DFS and RFS only in some cancer types and no generalized role could be predicted for all cancers.

Comparative Study on Clinicopathological Characteristics of Breast Cancer in Vietnam and Italy

Background: In Vietnam and Italy, breast cancer (BC) occurs in women more frequently than any other cancer. Vietnam has a substantially lower incidence of breast cancer than Italy, but a higher mortality rate. Most Vietnamese patients present to the hospital with severe tumors at the late stages of diagnosis. The purpose of this study was to compare clinicopathologic features, biomarkers, and subtypes of BC between Vietnamese women and Italian ones. Methods: The sample was collected from all Vietnamese patients undergoing surgery with the diagnosis of primary invasive breast carcinoma in Hue Central Hospital as well as Hue University Hospital in Vietnam during 1 year from April 2016 to April 2017, and from the same category of women in Sassari University Hospital, Italy during the year 2016. The study parameters in both groups consisted of age at diagnosis, tumor size, histologic grade, histologic type, axillary node status, stages of diagnosis, biomarkers (Estrogen Receptor - ER, Progesterone Receptor - PR, Ki-67 cell proliferation marker - Ki-67, Human epidermal growth factor receptor 2 - HER2), and molecular subtypes of BC. Results: 323 patients were collected in total (235 from Sassari, Italy, and 88 from Thua Thien - Hue province, Vietnam). Vietnamese patients were diagnosed at a younger age than Italian patients, at just 52.5 on average, while the figure for Italian was 62. The Vietnamese BC patients also had a bigger tumor in size, higher grade, more axillary node positivity as well as a later stage of disease in comparison with Italian ones. The proportion of ER-positive was higher in the Italian group than that in Vietnam (88.1 vs 55.7%). The high Ki-67 expression prevalence was significantly higher in Vietnamese patients compared with Italian (81.8 vs 45.1%). The HER2-positive rate in Vietnam was 33%, higher than that in Italy (8.1%). Histologic grade and cell proliferation index Ki-67 were significantly correlated with HER2 positivity in both groups. Conclusions: Vietnamese patients demonstrated more aggressive tumor features and worse prognostic biomarkers than Italian patients. The prevalence of HER2 positive and high Ki-67 expression in Vietnamese patients was considerably higher than in Italian patients. The remarkable differences in clinicopathological characteristics between the two populations suggest the diversity of biological tumor, ethnicity, and environment as well as the effectiveness of the screening program.

Chondroitin polymerizing factor predicts a poor prognosis and promotes breast cancer progression via the upstream TGF-β1/SMAD3 and JNK axis activation.

Aberrant composition of glycans in the tumor microenvironment (TME) contributes to tumor progression and metastasis. Chondroitin polymerizing factor (CHPF) is a glycosyltransferase that catalyzes the biosynthesis of chondroitin sulfate (CS). It is also correlated to transforming growth factor-β1 (TGF-β1) expression, a crucial mediator in the interaction of cancer cells with TME. In this study, we investigated the association of CHPF expression with the clinicopathological features of breast cancer (BRCA), as well the oncogenic effect and the underling mechanisms of CHPF upon BRCA cells. We found that CHPF expression is significantly increased in human BRCA tissues, and it is positively associated with TGF-β expression (r = 0.7125). The high-expression of CHPF predicts a poor prognosis and is positively correlated with tumor mass, lymph node metastasis, clinical staging and HER-2 negative-expression. The mechanistic study revealed that it promotes BRCA cell proliferation, migration and invasion through TGF-β1-induced SMAD3 and JNK activation in vitro, JNK (SP600125) or SMAD3 (SIS3) inhibitor can remove the promotion of CHPF upon cell proliferation, migration and invasion in MDA-MB-231 cells, which is derived from triple-negative breast cancer (TNBC). Collectively, our finding suggested CHPF may function as an oncogene and is highly expressed in human BRCA tissues. Pharmacological blockade of the upstream of JNK or SMAD3 signaling may provide a novel therapeutic target for refractory TNBC patients with CHPF abnormal high-expression.

The Role of Surgical Axillary Staging Prior to Immediate Breast Reconstruction in the Era of De-Escalation of Axillary Management in Early Breast Cancer.

Postmastectomy radiotherapy (PMRT) following immediate breast reconstruction (IBR) is associated with postoperative complications. Although the incidence of node-positive breast cancer is declining, a separate sentinel lymph node biopsy (SLNB) is still performed before mastectomy when IBR is planned, in order to evaluate nodal status and the need for PMRT. This study assessed the impact of staged SLNB on the breast reconstructive planning, and presents common clinicopathological characteristics of breast cancer with macrometastatic nodal spread where staged SLNB would be beneficial to indicate PMRT. Medical records of breast cancer patients scheduled for mastectomy and IBR at Skåne University Hospital, Sweden, from November 2014 to February 2020, were reviewed. Of 92 patients, node-positive disease was present in 15 (16%). Fifty-three patients underwent staged SLNB before mastectomy and IBR, and 10 (19%) presented with nodal metastasis. All patients with macrometastatic sentinel nodes were presented with palpable, multifocal, ER+ breast carcinoma of no special type with tumor size > 17.0 mm. Overall, four women received PMRT after verified metastasis by staged SLNB, and IBR was cancelled for three patients. These findings question the benefit of routine staged SLNB before mastectomy and IBR in breast cancer populations within established mammography screening programs with low risk of nodal metastasis.

Expression of SOX10 and GATA3 in breast cancer and their significance

Objective: To investigate the expression characteristics of SOX10 and GATA3 in breast cancer and the value of their combination. Methods: A total of 360 breast cancer specimens with SOX10 immunohistochemical staining were collected from the Department of Pathology in Shenzhen People's Hospital from 2018 to 2021, including 268 cases with simultaneous SOX10 and GATA3 staining. The expression of SOX10 and GATA3 in primary and metastatic breast cancer was detected, and the correlations between SOX10 and GATA3 and the molecular types and clinicopathological features of breast cancer were compared, and the distribution differences among each group were statistically analyzed. Results: The overall expression of SOX10 and GATA3 in breast cancer were 25.8%(93/360) and 81.7%(219/268), and that in triple negative breast cancer (TNBC) were 83.3%(80/96) and 42.7%(32/75), respectively. SOX10 was strongly associated with TNBC (P<0.001), whereas GATA3 was highly expressed in luminal A, luminal B and HER2 over expression breast cancers (P<0.001). The expression of SOX10 and GATA3 was negatively correlated in TNBC, and the combined expression rates of SOX10 and GATA3 in breast cancer and TNBC could reach 97.8% (262/268) and 94.7%(71/75), respectively. In addition, the expression of SOX10 was closely correlated with high histological grade, high Ki-67 proliferation index and lymph node metastasis, and negatively correlated with AR. The expression of GATA3 was correlated with low histological grade and lymph node metastasis, and positively correlated with AR, and the difference was statistically significant. Conclusions: SOX10 is a sensitive marker of TNBC, while GATA3 is highly expressed in non-triple negative breast cancer. The two complementary, combined application of SOX10-GATA3 can improve the detection rate of breast cancer, especially TNBC. SOX10 is associated with malignant characteristics of the tumor, suggesting that SOX10 can be used as a prognostic marker and potential therapeutic target for breast cancer.

Low CRIM1 Levels Predict Poor Prognosis in Breast Cancer Patients.

BackgroundCRIM1 is involved in the development and preservation of the nervous system, capillary development, and vascular maintenance. Although CRIM1 was reported to involve in multiple cancers, its role in breast cancer is unclear.MethodsWe investigated CRIM1 expression levels using Oncomine, HPA, and immunohistochemistry analyses. BC-GenExMiner was employed to evaluate the relationship of CRIM1 expression with the clinicopathological characteristics of breast cancer. Its association with breast cancer prognosis was assessed by Kaplan-Meier analysis and PrognoScan. The correlation of the expression of CRIM1 with tumor immune infiltration was explored via TIMER. Gene set enrichment analysis (GSEA) was utilized to determine the cascades that are linked to CRIM1 in breast cancer. Finally, we explored CRIM1 and its co-expressed genes using R (3.6.3).ResultsHere, we find that CRIM1 expression was downregulated in various subtypes of breast cancer, and it was lowest in triple-negative breast cancers. ER and PR status were positively correlated with CRIM1 expression, while HER-2 expression was negatively correlated with CRIM1 expression. But in our immunohistochemical results in breast cancer specimens collected from our laboratory, HER-2 expression was positively correlated with CRIM1 expression. The expression of CRIM1 was correlated with menopause status, T stage, pathologic stage, histological type, and P53 status but not with age, N-stage, M-stage, Radiation therapy, and BRCA1/2 status. Survival analysis found that low CRIM1 expression was correlated with poorer DMFS, RFS and OS. Notably, CRIM1 expression was positively linked to the level of infiltration by CD8+ T-cells, endothelial cells, and neutrophils, and negatively linked to NK, B-cells, CD4+ T-cells, tumor purity, macrophage M1, and Tregs. Besides, DIXDC1 and PFDN6 were correlated to CRIM1 possibly.ConclusionOur findings demonstrated that low CRIM1 expression predict poor prognosis of breast cancer and CRIM1 might be used as a possible treatment target or prognostic marker in breast cancer. More researches are needed to better understand the prognostic value of CRIM1 in breast cancer.

Association of Obesity and Luminal Subtypes in Prognosis and Adjuvant Endocrine Treatment Effectiveness Prediction in Chinese Breast Cancer Patients.

PurposeTo evaluate the influence of obesity on clinicopathological characteristics of breast cancer; to explore the effect of obesity on the prognosis and performance of endocrine therapy in breast cancer patients.MethodsPatients with luminal/HER2-negative early breast cancer were included and categorized into the non-obese (BMI<28kg/m2) and obese (BMI≥28kg/m2) groups according to body mass index (BMI). Clinicopathological characteristics and treatment modalities were compared between groups. Interaction of adjuvant endocrine therapy with obesity was analyzed.ResultsA total of 2,875 patients were included: 2,598 non-obese and 277 obese. A higher rate of patients with comorbidities (OR: 2.83, 95%CI 2.13-3.74, P<0.001) or PR-positive tumor (OR: 1.63, 95%CI 1.03-2.58, P=0.037) were identified in the obese group. Obesity was not associated with disease recurrence (P=0.839) or overall survival (P=0.140) in the whole population. Subgroup analysis did show an association with worse relapse-free survival (RFS, HR 3.48, 95%CI 1.31-9.22, P=0.012) and overall survival (OS, HR 4.67, 95%CI 1.28-16.95, P=0.019) in luminal A breast cancer. These results could not be reproduced in the luminal B subtype with a RFS (HR 0.78, 95%CI 0.41-1.49, P=0.454) or OS (HR 1.17, 95%CI 0.50-2.74, P=0.727). Furthermore, obesity did not impact endocrine therapy effectiveness in Tamoxifen or the aromatase inhibitor group (RFS: interact P=0.381; OS: interact P=0.888).ConclusionsThe impact of obesity on prognosis interacted with luminal subtype status in Chinese breast cancer patients which was not related with endocrine treatment modality.

Clinical and morphological features of breast tumors with PIK3CA mutations in Russian patients: Observational study

Background. By 2020, breast cancer (BC) has become the most frequent malignancy in the world. The most common type of BC is HR+/HER2-negative cancer,2540% of which harbors PIK3CA mutations that affect the catalytic subunit of the PI3K protein. PIK3CA alterations are actionable, as such neoplasms can be treated with a combination of fulvestrant and the PI3K inhibitor alpelisib. As PIK3CA mutations have an extremely versatile effect on the characteristics of a tumor cell, numerous associations of PIK3CA mutations and various clinico-pathological characteristics of BC can be traced.&#x0D; Aim. Our aim was to clarify the information on the frequency and spectrum of PIK3CA mutations in Russian patients with HR+/HER2- advanced BC, and to study the association of PIK3CA mutations with clinical and pathological parameters of BC.&#x0D; Materials and methods. Tissue samples from 694 patients with HR+/HER2- advanced BC (mixed population of primary metastatic and relapsed tumors) who received any line of anti-cancer treatment in Dec 2020 to June 2021 in Russian Federation were analyzed by high-resolution melting, allele-specific PCR, digital droplet PCR and Sanger sequencing (exons 7,9, and 20 of the PIK3CA gene). Mutation rates in different BC subgroups were compared using the Fishers exact test. The age at diagnosis in patients with different PIK3CA status was compared using the MannWhitney U-test. The relationship between the PIK3CA status and the degree of tumor differentiation was compared using the CochraneArmitage test for trends. Luminal A and B BC expression subtypes were distinguished with surrogate IHC markers according to St.-Gallen recommendations (2013).&#x0D; Results. Mutations were identified in 220/694 (32%) BC patients. The three most frequent missense substitutions in the PIK3CA gene (p.E542K, p.E545K, and p.H1047R) accounted for 190/220 (86%) mutations. Associations of PIK3CA mutations with luminal A subtype of BC, low proliferation index, small size of the primary tumor, and absence of signs of hereditary cancer were revealed. Associations of mutations in the kinase domain of PIK3CA (p.H1047R) with late recurrence of locally advanced BC and with non-Slavic ethnic origin of patients were found.&#x0D; Conclusion. PIK3CA mutation rate of 32% confirms high prevalence of mutation in Russian population, with some differences reflecting the ethnic origin of patients.

Relationship between the changes of positivity rate of HER2 expression and the diameter of invasive lesions in early breast cancer and its clinical significance

BackgroundThe expression status of HER2 is an important factor in evaluating the prognosis of breast cancer. We found that the positivity rate of HER2 varied with the diameter of invasive lesions in early breast cancer.We aimed to explore the relationship between the change of HER2 positivity rate of early breast cancer and the diameter of the invasive foci and its clinical significance. MethodsA total of 217 patients with microinvasive breast cancer and T1a stage breast cancer were enrolled in this study. Machine learning algorithm was used to extract morphological features of invasive lesions in early breast cancer. Using Spearman to analysis the clinicopathological and morphological features related to HER2 expression McNemar test was used to analyze the consistency of HER2 expression between the carcinoma in situ area and the invasive cancer area. ResultsIn early breast cancer, the diameter of the invasive foci was strongly negatively correlated with the expression status of HER2 (rho=−0.468, p < 0.001). As the diameter of the invasive foci increases, the HER2 positivity rate gradually decreases. When the diameter of the invasive foci> 2 mm, the positivity rate of HER2 was significantly reduced (from 52.6% to 16.1%, p < 0.001), which was close to the positivity rate of HER2 in ordinary invasive breast cancer. Moreover, most of the clinicopathological characteristics of breast cancer with an invasive lesion diameter of 1–2 mm and DCIS-MI were not significantly different (p > 0.05). Among 217 patients, the consistency rate of HER2 expression in carcinoma in situ and invasive foci areas was 97.7% (212/217), and there was no significant difference in HER2 expression status (p = 0.25 and p = 0.50, respectively). ConclusionsWe recommend that breast cancer with an invasive lesion diameter of 1–2 mm should be classified as microinvasive breast cancer. In early breast cancer,the expression status of HER2 in the invasive foci area can refer to the HER2 expression status in carcinoma in situ area. However, it needs further support from a large amount of data and follow-up results.

Circular RNAs as Potential Biomarkers in Breast Cancer.

Due to the high heterogeneity and initially asymptomatic nature of breast cancer (BC), the management of this disease depends on imaging together with immunohistochemical and molecular evaluations. These tests allow early detection of BC and patient stratification as they guide clinicians in prognostication and treatment decision-making. Circular RNAs (circRNAs) represent a class of newly identified long non-coding RNAs. These molecules have been described as key regulators of breast carcinogenesis and progression. Moreover, circRNAs play a role in drug resistance and are associated with clinicopathological features in BC. Accumulating evidence reveals a clinical interest in deregulated circRNAs as diagnostic, prognostic and predictive biomarkers. Furthermore, due to their covalently closed structure, circRNAs are highly stable and easily detectable in body fluids, making them ideal candidates for use as non-invasive biomarkers. Herein, we provide an overview of the biogenesis and pleiotropic functions of circRNAs, and report on their clinical relevance in BC.

ABCA8 inhibits breast cancer cell proliferation by regulating the AMP activated protein kinase/mammalian target of rapamycin signaling pathway.

ATP-binding cassette (ABC) subfamily A member 8 (ABCA8) has been reported to play a vital role in cancer development. Our study aimed to explore the role and the molecular mechanism of ABCA8 in breast cancer (BC) progression. GSE65194, GSE15852, and GSE45827 datasets were used to identify differentially expressed genes (DEGs) in BC. The diagnosis and prognosis value were determined using ROC curve analysis and Kaplan-Meier plotter, respectively. The relationship between ABCA8 expression and clinicopathological features in BC was analyzed by TCGA. Co-expressed genes of ABCA8 in BC were screened out through GEPIA and subjected to KEGG pathway enrichment analysis. Cell proliferation was evaluated by CCK-8 and EdU incorporation assays. Proliferating cell nuclear antigen (PCNA) expression and the changes of the AMP activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) pathway were measured by western blot analysis. Totally 4 overlapping DEGs were identified and all reduced in BC samples. ABCA8 with high diagnostic and prognostic values was selected for further exploration. Low ABCA8 expression was correlated with clinicopathological features in BC patients. ABCA8 overexpression inhibited BC cell proliferation. The top 20 co-expressed genes of ABCA8 were identified by GEPIA and significantly enriched in AMPK signaling pathway. Inhibition of AMPK/mTOR pathway reversed the suppressive effect of ABCA8 on BC cell growth. These results suggested that ABCA8 overexpression repressed BC cell proliferation through regulating the AMPK/mTOR signaling pathway.

Transcribed Ultraconserved Regions Are Associated with Clinicopathological Features in Breast Cancer.

Ultraconserved regions (UCRs) are 481 genome segments, with length longer than 200 bp, that are 100% conserved among humans, mice, and rats. The majority of UCRs are transcriptionally active (T-UCRs) as many of them produce non-coding RNAs. In a previous study, we evaluated the expression level of T-UCRs in breast cancer (BC) patients and found that 63% of transcripts correlated with some clinical and/or molecular parameter of BC. In this study, we delved into the expression levels of 12 T-UCRs and correlated them with clinicopathological parameters, immunohistochemical markers, and overall survival in two breast cancer cohorts: TCGA and Brazilian patients. We found that uc.268 is more expressed in TCGA patients under 40 years of age, associated with progesterone receptor (PR) and estrogen receptor (ER), and its high expression is found in luminal A. Lower uc.84 and uc.376 were respectively observed in metastatic and stage IV tumors associated with good prognostic in luminal B. Moreover, uc.84 was only related to the HER2+, while uc.376 was related to ER+ and PR+, and HER2+. A panel composed of uc.147, uc.271, and uc.427 distinguished luminal A from triple negative patients with an AUC of 0.9531 (sensitivity 92.19% and specificity 86.76%). These results highlight the potential role of T-UCRs in BC and provide insights into the potential application of T-UCRs as biomarkers.

Associations of CXCL12 polymorphisms with clinicopathological features in breast cancer: a case-control study

BackgroundPrevious studies suggested that CXCL12 was involved in the development, metastasis, and invasion of breast cancer, and genetic variants were associated with the diagnosis and prognosis of patients with breast cancer. The present study was aimed to assess the relationships between CXCL12 polymorphisms (rs1801157, rs2297630, and rs2839693) and susceptibility and clinicopathological features of breast cancer.MethodsA case-control study was conducted in 434 breast cancer patients and 450 health controls. Student t-test and chi-square test were used to analyze the differences of age distribution and genotype frequencies between the two groups. Correlations between polymorphisms and clinical parameters were also assessed by chi-square test. The potential effects of the three polymorphisms on CXCL12 were investigated by the public database.ResultsA statistical association was found between CXCL12 rs1801157 polymorphism and breast cancer risk, possibility of metastasis, and estrogen receptor status. Patients with rs2839693 C/T or C/T-T/T genotypes were more likely to be progesterone receptor-negative. However, no associations of rs2297630 polymorphism with breast cancer risk or any clinicopathological characteristics were observed. In addition, rs2297630 affected the splicing quantitative trait loci of CXCL12 in the subcutaneous fat, rs2839693 polymorphism affected the splicing quantitative trait loci of CXCL12 in the human breast mammary tissues.ConclusionsThose results indicated that CXCL12 polymorphisms might be potential diagnostic indicators, and more investigation is needed in the future.

Molecular Profile and Clinico-pathological Characteristics of Breast Cancer in Central India: First Investigative Report.

Stage at presentation and molecular profile are the two most important factors affecting breast cancer prognosis. This is the first study on molecular breast cancer subtypes from Central India. We prospectively reviewed 260 consecutive breast cancer patients diagnosed at the Department of Surgery, Government NSCB Medical College, Jabalpur (MP), between January 2017 and December 2020. Clinico-pathological and molecular profiles and their associations with the characteristics of the tumor were analyzed. The median age at diagnosis was 44.7years (range 21-93). Eleven percent (n = 11) were in clinical stage I, 12.7% (n = 12) were in stage II, 56% (n = 146) in stage III, and 20% (n = 52) were in stage IV. Metastatic lymph node positivity rate was 85% at the time of diagnosis. Luminal subtype was present in 50% (n = 131), Her 2 neu-enriched type in 21.5% (n = 55), and triple-negative subtype in 28.5% (n = 74). A stronger association was observed for each increasing clinical stage for Her 2 neu-enriched and triple-negative breast cancer (TNBC) but not luminal-type tumors. For grade of tumors, patients with luminal subtype had a higher percentage of lower grades (p = .001); however, Her 2-enriched and TNBC had higher proportion of grade III tumors (for Her 2-enriched p = .04, TNBC p = .001). In Central India, like other regions of India, breast cancer occurs at an earlier age and is diagnosed at a more advanced stage. In this region, pre-menopausal breast cancer is more common than post-menopausal and TNBC tumors have similar incidence in pre-menopausal and postmenopausal women.

Association of vitamin D deficiency and inflammatory cytokines with the clinicopathological features of breast cancer in female Saudi patients

Breast cancer is the leading cause of cancer-related death among women in Saudi Arabia. Many studies have suggested a strong correlation between vitamin D and multiple types of cancer. This study included 100 female Saudi patients with early or locally advanced breast cancer. Patients were recruited from King Faisal Hospital in Taif City, Saudi Arabia, from January 2020 to September 2020. We aimed to study the association between serum vitamin D, calcium, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α) and chemerin and breast cancer progression. The control group consisted of 100 healthy individuals. Serum levels of vitamin D, calcium, IL-6, TNF-α and chemerin were measured in all participants. Vitamin D was significantly decreased in patients with high-grade tumours ( p &lt; 0.0001), obesity ( p = 0.013), negative oestrogen receptors ( p &lt; 0.0001), negative progesterone receptors ( p &lt; 0.0001) and positive HER2 receptors ( p &lt; 0.0001). Vitamin D was also decreased in patients with large tumours ( p &lt; 0.0001), axillary lymph node involvement ( p &lt; 0.0001) and advanced-stage cancers ( p &lt; 0.0001). Moreover, higher levels of IL-6, TNF-α and chemerin were significantly associated with the presence of breast cancer, particularly in its advanced stages. Vitamin D deficiency and elevated levels of IL-6, TNF- α and chemerin were associated with adverse clinicopathological features of breast cancer. Vitamin D deficiency and elevated inflammatory cytokines (IL-6, TNF-α and chemerin) were associated with the clinicopathological features of breast cancer in female Saudi patients.

Estrogen-Related Receptors Gene Expression and Copy Number Alteration Association With the Clinicopathologic Characteristics of Breast Cancer

Purpose:It has been suggested that dysregulation of transcription factors expression or activity plays significant roles in breast cancer (BC) severity and poor prognosis. Therefore, our study aims to thoroughly evaluate the estrogen-related receptor isoforms (ESRRs) expression and copy number alteration (CNA) status and their association with clinicopathologic characteristics in BC.Methods:A METABRIC dataset consist of 2509 BC patients’ samples was obtained from the cBioPortal public domain. The gene expression, putative CNA, and relevant tumor information of ESRRs were retrieved. ESRRs messenger RNA (mRNA) expression in BC cell lines was obtained from the Cancer Cell Line Encyclopedia (CCLE). Association and correlation analysis of ESRRs expression with BC clinicopathologic characteristics and molecular subtype were performed. Kaplan–Meier survival analysis was conducted to evaluate the prognostic value of ESRRs expression on patient survival.Results:ESRRα expression correlated negatively with patients’ age and overall survival, whereas positively correlated with tumor size, the number of positive lymph nodes, and Nottingham prognostic index (NPI). Conversely, ESRRγ expression was positively correlated with patients’ age and negatively correlated with NPI. ESRRα and ESRRγ expression were significantly associated with tumor grade, expression of hormone receptors, human epidermal growth factor receptor 2 (HER2), and molecular subtype, whereas ESRRβ was only associated with tumor stage. A significant and distinct association of each of ESRRs CNA with various clinicopathologic and prognostic factors was also observed. Kaplan–Meier survival analysis demonstrated no significant difference for survival curves among BC patients with high or low expression of ESRRα, β, or γ. On stratification, high ESRRα expression significantly reduced survival among premenopausal patients, patients with grade I/II, and early-stage disease. In BC cell lines, only ESRRα expression was significantly higher in HER2-positive cells. No significant association was observed between ESRRβ expression and any of the clinicopathologic characteristics examined.Conclusions:In this clinical dataset, ESRRα and ESRRγ mRNA expression and CNA show a significant correlation and association with distinct clinicopathologic and prognostic parameters known to influence treatment outcomes; however, ESRRβ failed to show a robust role in BC pathogenesis. ESRRα and ESRRγ can be employed as therapeutic targets in BC-targeted therapy. However, the role of ESRRβ in BC pathogenesis remains unclear.

Correlation of clinicopathological features of breast cancer with Molecular Subtypes taking Ki-67 into consideration: Single institution experience over 5 years

Introduction: Molecular classification of breast cancer is commonly done to determine response to therapy and cancer prognosis. Aim of the study was to compare prevalence of molecular subtypes of breast cancer in our institute using immunohistochemistry, including Ki-67, and corelate it with clinical and pathological prognostic factors.