Clinicopathological Features Of Breast Cancer Research Articles

Association of Human Papilloma Virus, Cytomegalovirus, and Epstein–Barr Virus with Breast Cancer in Jordanian Women

Background and Objectives: The investigation of oncogenic viruses and their potential association with breast cancer (BC) remains an intriguing area of study. The current work aims to assess evidence of three specific viruses, human papillomavirus (HPV), cytomegalovirus (CMV), and Epstein–Barr virus (EBV) in BC samples and to explore their relationship with relevant clinicopathological variables. Materials and Methods: The analysis involved BC samples from 110 Jordanian female patients diagnosed with BC and breast tissue samples from 30 control patients with no evidence of breast malignancy, investigated using real-time PCR. The findings were then correlated with various clinico-pathological characteristics of BC. Results: HPV was detected in 27 (24.5%), CMV in 15 (13.6%), and EBV in 18 (16.4%) BC patients. None of the control samples was positive for HPV or CMV while EBV was detected in only one (3.3%) sample. While (HPV/EBV), (HPV/CMV), and (EBV/CMV) co-infections were reported in 1.8%, 2.7%, and 5.5%, respectively, coinfection with the three viruses (HPV/CMV/EBV) was not reported in our cohort. A statistically significant association was observed between HPV status and age (p = 0.047), and between clinical stage and CMV infection (p = 0.015). Conclusions: Our findings indicate the presence or co-presence of HPV, CMV, and EBV in the BC subpopulation, suggesting a potential role in its development and/or progression. Further investigation is required to elucidate the underlying mechanisms that account for the exact role of oncoviruses in breast carcinogenesis.

SLC35A2 expression is associated with HER2 expression in breast cancer

The role of SLC35A2 in breast cancer remains poorly understood, with limited available information on its significance. This study aimed to investigate the expression of SLC35A2 and clinicopathological variables in breast cancer patients. Immunohistochemical analysis of SLC35A2 protein was conductedon 40 adjacent non-neoplastic tissues and 320 breast cancer tissues. The study also assesed the association between SLC35A2 expression and breast cancer clinicopathological features of breast cancer, as well as its impact on overall survival. In comparison to adjacent non-neoplastic tissues, a significantly higher expression of SLC35A2 was observed in breast cancer tissues (P = 0.020), and this expression was found to be independently correlated with HER2 positivity (P = 0.001). Survival analysis indicated that patients with low SLC35A2 expression had a more favorable prognosis in HER2-positive subtype breast cancer (P = 0.017). These results suggest that SLC35A2 is overexpressed in breast cancer tissues compared to adjacent non-neoplastic tissues and may serve as a potential prognostic marker for HER2-positive subtype breast cancer. Furthermore, breast cancer patients with the HER2 positive subtype who exhibited decreased levels of SLC35A2 expression demonstrated improved long-term prognostic outcomes.

Uncovering the relationship between YAP/ WWTR1 (TAZ) genes expression and LncRNAs of SNHG15, HCP5 and LINC01433 in breast cancer tissues

In spite of the decrease in breast cancer (BC) death rates, it has remained a significant public health concern. Dysregulation of the Hippo pathway contributes to breast cancer development and progression by enhancing cancerous cell proliferation, survival, invasion, and migration. Investigating the connection between specific lncRNAs (SNHG15, HCP5, and LINC01433) and YAP and WWTR1, and the impact of these lncRNAs on the expression of YAP and WWTR1 proteins in the Hippo pathway, may offer valuable understanding for BC diagnosis and treatment. Forty BC tissue samples were acquired from the Tumor Bank and utilized for RNA and protein extraction. Real-time PCR and western blotting techniques were performed to assess the gene and protein expressions, respectively. Correlations between variables and their associations with clinicopathological features in BC were evaluated using Mann-Whitney U or Student's t-test. Additionally, the analysis of the GEO database was utilized to validate the findings. In cancerous tissue, the up-regulation of YAP, WWTR1, HCP5, SNHG15, and Linc01433 at both the mRNA and protein levels corresponds to the findings in GEO datasets. A significant association was found between YAP and histological grade, while WWTR1 showed a correlation with family history and HER-2. The distinct and notable expression of YAP, WWTR1, SNHG15, HCP5, and Linc01433 in BC tissues, together with the results of combined ROC curve analysis derived from our finding and GEO database suggest that a combined panel of these 5 RNAs may have great potential in predicting of BC and its management.

Abstract 3014: Exploring the correlation between oncogenic viruses and BRCA1/2gene mutations in Egyptian breast cancer patients

Abstract Background: Recognizing the complexity of viral carcinogenesis and its perspectives, we aimed to investigate one of the key genetic factors associated with breast cancer development, BRCA1,2 mutations, and its association with the presence of some oncogenic viruses like HPV, MMTV, and EBV DNAs in both blood and tissues of breast cancer (BC) patients, hoping to provide new insights on role of oncogenic viruses in cancer development. Patients and Methods: This study was conducted on 84 tissues and blood samples from Egyptian BC women and 50 blood samples from controls without known oncological disease. All samples were tested for the presence of viral DNAs, using real-time PCR assay. Fifty-five BC patients were investigated for the presence of mutations in exons 6 and 9 of BRCA1, and exons 11, 14, and 27 of BRCA2 using a high-resolution melting (HRM) assay. Results were correlated with the clinicopathological characteristics of BC. Results. HPV, MMTV, and EBV DNAs were detected in 30(35.7%), 19(22.6%), and 23 (27.3%) of tissues obtained from 84 BC patients, respectively, and into 16 (19%), 14 (16.7%) and 0 (0%) of blood from the same patients, respectively. On the other hand, these viruses were detected in 0 (0%), 7 (14%), and 0 (0%) of blood specimens obtained from 50 normal controls, respectively. Among 55 BC patients, mutations were detected in 37 (67%) of the tested exons of BRCA1/2 genes in the blood of BC patients, divided as 7 (12.7%) for exons 6 and 9 of BRCA1 gene, and into 11 (20%), 3 (5.5%), and 9 (16.4%) for exons 11, 14 and 27 of BRCA2 gene. Our previous investigation based on NGS showed that pathogenic mutations were (G509A:p.R170Q and c.C1471T:p.Q491X) for exons 6, 9 of BRCA1, respectively, and were (cT4001A: p.L1334X, c.7231delA: p.T2412Lfs and c.T9861A: p.C3287x) for exons 11, 14 and 27 of BRCA2, respectively. Further analysis showed that half of the patients with positive HPV DNA in tissues had mutations in the tested exons of BRCA1/2 genes. In contrast, none of the patients with MMTV DNA (15/55 (27%)) in their tissues had mutations in exons 6 and 9 of BRCA1 and only one patient had a mutation in exons 11 of BRCA2. Regarding EBV, 35% of positive patients had mutations in the tested exons of the BRCA1 gene and 21% in the tested exons of BRCA2 gene. Results were not affected by clinicopathological parameters. Conclusion: MMTV DNA followed HPV, and then EBV DNAs were detected in more than 80% of our BC patients. HPV was the most frequent virus among BC patients showed to be associated with BRCA1/2 mutations in the tested exons. Sequencing analysis is in progress. Understanding this association will provide a relevant implication for developing novel, and personalized therapeutic options for treatment of oncogenic viruses. Citation Format: Samah Loutfy, Rania Abdulmonem Al Najar, Sarah ElSayed, Nasra Abdel Fattah, Ayman Abdel-Samie Gaber, Tarek Hashem, Wafaa S. Khalaf, Ahmed F. Basyony, Amany El-Sharif, Sahar Mohamed Ramzy Radwan, Mohamed Eltokhy. Exploring the correlation between oncogenic viruses and BRCA1/2gene mutations in Egyptian breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3014.

The epidemiological and clinicopathological features of breast cancer in Riyadh, Saudi Arabia.

To investigate the epidemiological and clinicopathological features of breast cancer (BC) in Saudi Arabia to improve decisions regarding resource allocation, disease control, and management. We retrieved the records of all patients who presented with histologically proven BC at King Fahad Medical City between 2019 and 2020. The data were analyzed quantitatively, and the results were expressed as percentages and frequencies. This study comprised 419 patients. The mean age was 50.13 (± 10.96) years. The majority of the patients were obese (56.6%), and approximately a quarter had a history of oral contraceptive pill use, breast biopsy, or an affected family member. Most cases were from the central region (80.1%), followed by the southern provinces (12.7%). Breast lumps were the most common complaint (89%), whereas hypertension and diabetes mellitus were the most common comorbidities. Invasive ductal carcinoma was the most common pathologic type (89.7%). Most patients presented with TNM stages II and III (55.2%), and 27.7% had metastasis. The main therapeutic modalities included radical mastectomy (63.8%), neoadjuvant chemotherapy (60.4%), and adjuvant radiotherapy (82.9%). In Saudi Arabia, a trend of BC incidence migration towards older patients may be ensuing. However, prediction of an advanced and aggressive presentation requires the enhancement of screening programs and standardized protocols for disease management.

Association of Positive Family History and Clinicopathological Features in Breast Cancer in Young Indian Females – A Pilot Study

ABSTRACT Introduction: Breast cancer is the most common cancer in Indian females, accounting for 31.8% of all cancers. Young women with breast cancer are those under 40 years of age. These patients have higher chances of positive family history and genetic susceptibility. Approximately 5%–10% of cases of breast cancer are associated with a family history. In this study, we planned to identify a relationship between family history and the clinical, pathological, and genetic characteristics of breast cancer in young women. Methods: Retrospectively, data from patients aged < 40 years with breast cancer, were collected from 2019 to 2022. Detailed information about the family history of the patients including the degree and number of relatives affected and the types of cancer was recorded. The tumors were characterized based on the pathological grade, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status, and BRCA variant genetic analysis. Results: Of 125 females with young breast cancer, 24 patients (19%) had a first- or second-degree relative with a history of cancer at the time of breast cancer diagnosis. Four (16%) of these positive cases had BRCA mutation detected. Bilateral breast cancer was detected in 12% of women with positive family history. Conclusion: Clinicians are urged to use detailed family histories for young women with breast cancer for early screening and education of the first- and second-degree relatives of these patients to detect the hidden cases.

Correlation Between Messenger RNA Expression and Clinicopathological Features of Breast Cancer: A systematic review.

Meta analysis was adopted to investigate the correlation between messenger ribonucleic acid (mRNA) expression and clinicopathological features of breast cancer (BC). English databases, PubMed, Web of Science, Embase, and The Cochrane Library, etc., were searched using a computer. The time range of retrieval was set to be from the establishment of the database to December 2023. The search terms were set as "mRNA", "Breast cancer", "Pathology", "Clinicopathological characteristics", etc. The literatures were screened in line with the inclusion and exclusion criteria, and the data was extracted for analysis by Revman5.3. Finally, 5 suitable included literatures were selected, including 969 patients. The analysis results were found to reveal a significant association between mRNA expression and BC grading (OR = 0.11, 95% CI = 0.04-0.30, Z = 4.26, P<0.0001); a significant correlation was observed between mRNA expression and BC staging (OR = 0.19, 95% CI = 0.05-0.65, Z = 2.65, P = 0.008<0.05); no correlation was found between mRNA expression and menstrual status of BC patients (OR = 0.63, 95% CI = 0.22-1.78, Z = 0.88, P = 0.38>0.05); a correlation was identified between mRNA expression and tumor size in BC (OR = 0.48, 95% CI = 0.24-0.99, Z = 2.00, P = 0.05). In the Discussion section, this study, comprising 10 research studies, aimed to explore the correlation between messenger ribonucleic acid and the clinical pathological features of BC. staging and grading of BC, a certain correlation with tumor size, and no correlation with the menstrual status of BC patients.

Relevance Analysis of TPM2 and Clinicopathological Characteristics in Breast Cancer.

The function of tropomyosin 2 (TPM2) in breast cancer is still far understudied. In this study, we aim to explore the roles of TPM2 in breast cancer progression. This research included 155 breast cancer tissues. The expression of TPM2 was analyzed by immunohistochemical staining and grading. The mRNA expression of TPM2 in pan-cancer was analyzed with The Cancer Genome Atlas (TCGA) data plate form. The differential expression of TPM2 protein and the differential promoter methylation level of TPM2 between breast cancer tissues and normal breast tissues were analyzed by the UALCAN online database. The relationship between TPM2 and signaling pathways was interpreted by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) pathway enrichment analyses. The survival curve of TPM2 was analyzed across the Kaplan-Meier plotter online database. Furthermore, the relationship between TPM2 expression and infiltrating macrophages was validated through in vitro co-culture experiments. TPM2 expression was significantly down-regulated in breast cancer samples. In addition, TPM2 expression was correlated with lymph node metastasis and high-grade histopathological morphology. The receiver operating characteristic (ROC) curve indicated that TPM2 expression could well distinguish between normal breast tissue and breast cancer tissue. TPM2 may have potential value in breast cancer diagnosis. Bioinformatics analysis illustrated that TPM2 was mainly involved in extracellular matrix organization, collagen fibril organization, cell junction assembly, focal adhesion, cAMP signaling pathway, estrogen signaling pathway, Wnt signaling pathway, and adaptive immune system. TPM2 expression was correlated with immune infiltrating cells and immune checkpoint molecules. Our in vitro co-culture experiments showed that the M2 macrophages could upregulate the expression of TPM2. TPM2 may play key roles in breast cancer occurrence and development, especially in cancer metastasis. TPM2 may be a potential biomarker for breast cancer diagnosis.

Expression analysis of lymphocyte subsets and lymphocyte-to-monocyte ratio: reveling immunosuppression and chronic inflammation in breast cancer

ObjectiveTo explore the immune status and chronic inflammation of breast cancer patients, this study aims to analyze the diagnostic value of peripheral blood lymphocyte subsets (CD3+T, CD4+T, CD8+T, CD3+CD4−CD8−T, CD19+B, and NK cells) and lymphocyte-to-monocyte ratio (LMR) for breast cancer. Furthermore, it seeks to examine the correlation between these subsets and LMR with clinicopathological features.MethodsA total of 100 breast cancer patients were selected as the experimental group, while 55 patients with benign breast diseases were included in the control group. Statistical analysis, including the Wilcoxon test, Kruskal–Wallis test and the receiver operating characteristic curve, was employed to investigate the association between these serum indexes and the clinicopathological characteristics of the patients.ResultsThe levels of CD3+T cells, CD4+T cells, CD8+T cells, CD4+/CD8+ ratio, NK cells, CD3+CD4−CD8−T cells, and LMR were found to be related to the occurrence of breast cancer when analyzing data from patients with benign and malignant breast diseases. Among these biomarkers, CD3+T cells, CD4+T cells, CD4+/CD8+ ratio, CD3+CD4−CD8−T cells, and LMR were identified as independent risk factors for breast cancer development, and the AUCs were 0.760, 0.750, 0.598, 0.697, and 0.761 (P < 0.05), respectively. Furthermore, we observed varying degrees of differences in the expression of CD3+T cells, CD4+T cells, CD8+T cells, CD4+/CD8+ ratio, and LMR in lymph node metastasis, clinical staging, molecular typing, Ki-67 level (P < 0.05). However, statistical differences in histologic grade and pathology type were not found (P ≥ 0.05).ConclusionLymphocyte subsets and LMR reflect the immune status and chronic inflammation of the body, respectively. They have certain value in the diagnosis of benign and malignant breast diseases, and correlate with lymph node metastasis, clinical staging, molecular typing and other clinicopathological features of breast cancer. Therefore, monitoring the expression of lymphocyte subsets and LMR in the body may help the auxiliary diagnosis and condition analysis of breast cancer in the clinic.

Expression and clinical diagnostic value of CCHE1 in breast cancer.

Breast cancer is a malignant tumor in the epithelial tissue of the breast gland. This study aimed to unveil the expression and clinical diagnostic value of lncRNA cervical cancer high-expressed 1 (CCHE1) in breast cancer. CCHE1 expression in breast cancer tissues was evaluated by RT-qPCR. The relationship between the CCHE1 expression and clinicopathological features of breast cancer was analyzed with the chi-square test, and the survival of breast cancer patients was evaluated with the Kaplan-Meier method. The diagnostic value of CCHE1 expression for breast cancer was evaluated by using the receiver operating characteristics (ROC) curve. Breast cancer cell lines (SKBR3, T47D, BT474, and MCF-7) were cultured for detecting CCHE1 expression in the cells. MCF-7 cells were selected for the subsequent experiments, and the small interfering RNA of CCHE1 (si-CCHE1) and CCHE1 overexpression vector (pcDNA-CCHE1) were transfected into MCF-7 cells. The proliferation, migration, and invasive ability were assessed by CCK-8 and Transwell assays. The influence of CCHE1 on the growth of tumors was validated by nude mice xenograft assay. CCHE1 was up-regulated in breast cancer tissues and breast cancer cells. The high expression level of CCHE1 in cancer tissues of breast cancer patients was correlated with larger tumor size, advanced TNM stage, Ki-67 status, and lymph node metastasis. The area under the ROC curve for CCHE1 in the diagnosis of breast cancer was 0.983 (95% CI: 0.966-1.000), with a sensitivity of 95.00% and a specificity of 91.70%. The 5-year survival rate was higher in patients with low CCHE1 expression than those with high CCHE1 expression. Furthermore, restrained CCHE1 impeded proliferation, invasion, and migration of MCF-7 cells, as well as tumor growth in mice. Our study highlights that elevated expression of CCHE1 in breast cancer tissues, which is closely related to clinicopathologic features, has some clinical value in the diagnosis of the disease.

Molecular subtypes and clinicopathological features of breast cancer in Libya: a first glance

Molecular subtypes and clinicopathological features of breast cancer in Libya: a first glance

Prognostic value of glucose transporter proteins-1 (GLUT1) in breast carcinoma

ABSTRACT Several studies have reported increased glucose transporters (GLUT) expression in different cancer types, including breast cancer. The primary purpose of this study is to examine GLUT1 immunoexpression in breast cancer patients in Saudi Arabia and to determine its significance. The study examined the association between GLUT1 immunophenotype and the clinicopathological characteristics in breast cancer. GLUT1 expression was analyzed in retrospectively collected tissue samples (n = 578) from breast cancer patients using immunohistochemistry. A total of 311 (54%) of the cases expressed GLUT1 cytoplasmic immunohistochemical staining. In univariate analysis, we found a significant association between GLUT1 expression and high-grade tumors (p < 0.0001). Positive estrogen and progesterone receptor results predicted lower GLUT1 immunoexpression (p < 0.0001 for both). Vascular invasion showed a significant association with GLUT1 immunoexpression (p = 0.045). Our findings support that GLUT1 immunohistochemistry can be used as a marker to determine the grade and hormonal receptor status in breast cancer.

Predictive Significance of Systemic Immune-Inflammation Index in Patients with Breast Cancer: A Retrospective Cohort Study.

Peripheral blood inflammation indices, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), have become research hotspots in the diagnosis, treatment, and prognosis prediction of breast cancer, whereas existing research findings remain controversial. Data pertaining to 1808 breast cancer patients were collected retrospectively to analyze the predictive value of NLR/PLR/SII for breast cancer clinicopathological characteristics, chemotherapy response, and relapse. 1489, 258, and 53 eligible breast cancer patients entered into the three analyses, respectively. Logistic regression analyses were used to assess the correlation between these indices and poor response to chemotherapy. A predictive scoring model was established to predict chemotherapeutic responses based upon the odds ratio values of significant variables identified in logistic regression analyses. Higher pretherapeutic NLR/PLR/SII values were significantly correlated with higher tumor stage, triple-negative breast cancer, premenopausal status, and younger age. Logistic regression analyses indicated that pretherapeutic high SII (as a continuous variable or with a cut-off value of 586.40) and HER2-negative status were independent predictors of poor response to neoadjuvant chemotherapy. A first-in-class SII-based predictive scoring model well distinguished patients who might not benefit from neoadjuvant chemotherapy, with an area under the curve of 0.751. In HR-positive cancers, SII was more strongly associated with clinicopathological features and chemotherapy response. In addition, a receiver operating characteristic curve analysis indicated that the specificity of follow-up SII in identifying cancer relapse was greater than 98.0% at a cut-off value of 900. As a predictor of breast cancer, especially in the HR-positive subtype, SII may eclipse NLR/PLR. SII-high patients are more likely to have a worse chemotherapy response and a higher risk of recurrence.

Expression and significance of effector proteins NLRP3 and gasdermin D N-terminal protein in the pyrolysis pathway in breast cancer.

To detect the expression and significance of GSDMD-N (gasdermin D N-terminal) in breast cancer, along with pyroptosis effector protein NLRP3 (nucleotide-binding oligomerization domain-like receptor protein 3), and determine their relationship with the clinicopathological characteristics of breast cancer. From January 2014 to December 2014, NLRP3 and GSDMD-N expression in 90 breast carcinoma organism samples and 30 paracancer tissues in the Department of Pathology. The First Affiliated Hospital of Bengbu Medical College was assessed using immunohistochemistry. The method of Kaplan-Meier was employed for the sake of comparing the survival between NLRP3 and GSDMD-N protein low and high expression groups. Among the breast cancerous organisms, the relationship between the expression of NLRP3 and GSDMD-N, corresponding adjacent tissues, and various clinicopathological features was analyzed using the χ2 and Spearman rank correlation tests. In the 90 breast cancer tissue samples, the pyrolysis pathway effector proteins GSDMD-N and NLRP3 were actively associated; and, expression intensities of NLRP3 and GSDMD-N were shown to be correlated with breast cancer. In addition, the clinicopathological features of patients were shown to be correlated with breast cancer. Notably, the higher the expressions of NLRP3 and GSDMD-N, the lower the risk of death of patients with breast cancer and the better the prognosis. The expression of the pyrolysis effector proteins NLRP3 and GSDMD-N in breast cancer tissues may take the lead in tumor prognosis in patients with breast cancer.

The expression of matrix metalloproteinase 2, 9 and 11 in Ethiopian breast cancer patients

IntroductionMatrix metalloproteinases (MMPs) play a pathophysiological role in cancer initiation and progression. Numerous studies have examined an association between MMP-2, MMP-9, and MMP-11 expression and clinicopathological characteristics of breast cancer (BC); however, no research has been done on the MMP expression levels in BC cases from Ethiopia.Materials and methodsA total of 58 formalin-fixed paraffin-embedded breast tissue samples encompassing 16 benign breast tumors and 42 BC were collected. The RNA was extracted and quantitative reverse-transcription PCR was performed. GraphPad Prism version 8.0.0 was used for statistical analysis.ResultsThe MMP-11 expression levels were significantly higher in breast cancer cases than in benign breast tumors (P = 0.012). Additionally, BC cases with positive lymph nodes and ER-positive receptors had higher MMP-11, MMP-9, and MMP-2 expression than cases with negative lymph nodes and ER-negative, respectively. The MMP-11 and MMP-9 expressions were higher in grade III and luminal A-like tumors than in grade I-II and other subtypes, respectively.ConclusionThe MMP-11 expression was higher in BC than in benign breast tumors. Additionally, MMP-11, MMP-9, and MMP-2 were higher in BC with positive lymph nodes and estrogen receptors. Our findings suggest an important impact of MMPs in BC pathophysiology, particularly MMP-11.

Epidemiology and clinicopathologic features of breast cancer in China and the United States.

Breast cancer has kept increasing since the past decades and the incidence rate is the highest among all neoplasms nowadays. China, as well as other countries, faces severe burden from the increasing population with breast cancer. This study aimed to analyze the epidemiology and clinicopathologicfeatures of breast cancer in China and the United States (US). Data of hospitalized patients diagnosed with primary breast cancerbetween 1 January 1999 and 31 December 2014 in the Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) were reviewed. Clinical and demographic data were extracted from medical history systems, and the sixteen-year trends wereanalyzed. Meanwhile, retrieveddata from the Surveillance, Epidemiology, and End Results (SEER) database from 1999 to 2014 were used for comparisons. A total of 18,768 breast cancer patients were included from CHCAMS, China, with 18,685 female cases (99.57%) and 81 male cases (0.43%). A total of 762,954 breast cancer patients were included from the SEER database, US, with 757,357 female cases (99.27%) and 5,597 male cases (0.73%). The peak age of breast cancer was 45-49 years old from 1999 to 2014 in China, while the peak age was 55-59 years from 1999 to 2006 and 60-64 years from 2007 to 2014 in the US. There were more young (<35 years, 6.56% vs. 1.97%, P<0.001), less elderly (≥65 years, 9.99% vs. 40.88%, P<0.001), less stage I (24.93% vs. 48.84%, P<0.001) and more stage III (21.00% vs. 12.35%, P<0.001) breast cancer patients in China than in the US. Patients aged 30-49 years old had a decreased trend (P<0.001), while 55-64 years old patients had an increased trend (P<0.001) from 1999 to 2014 in China, the same trend was also observed in the US. Mucinous carcinoma and histological grade I breast cancer patients increased with age both in China and the US (P<0.001). The unique epidemiology and clinicopathologic features of breast cancer (earlier peak age, more younger patients, more advanced stage, etc.), as well as the typical trend in China, should be seriously recognized, so as to guide future prevention and management strategies.

High HSPB1 expression predicts poor clinical outcomes and correlates with breast cancer metastasis

BackgroundHeat shock protein beta-1 (HSPB1) is a crucial biomarker for pathological processes in various cancers. However, the clinical value and function of HSPB1 in breast cancer has not been extensively explored. Therefore, we adopted a systematic and comprehensive approach to investigate the correlation between HSPB1 expression and clinicopathological features of breast cancer, as well as determine its prognostic value. We also examined the effects of HSPB1 on cell proliferation, invasion, apoptosis, and metastasis.MethodsWe investigated the expression of HSPB1 in patients with breast cancer using The Cancer Genome Atlas and immunohistochemistry. Chi-squared test and Wilcoxon signed-rank test were used to examine the relationship between HSPB1 expression and clinicopathological characteristics.ResultsWe observed that HSPB1 expression was significantly correlated with the stage N, pathologic stages, as well as estrogen and progesterone receptors. Furthermore, high HSPB1 expression resulted in a poor prognosis for overall survival, relapse-free survival, and distant metastasis-free survival. Multivariable analysis showed that patients with poor survival outcomes had higher tumor, node, metastasis, and pathologic stages. Pathway analysis of HSPB1 and the altered neighboring genes suggested that HSPB1 is involved in the epithelial-to-mesenchymal transition. Functional analysis revealed showed that transient knockdown of HSPB1 inhibited the cell migration/invasion ability and promoted apoptosis.ConclusionsHSPB1 may be involved in breast cancer metastasis. Collectively, our study demonstrated that HSPB1 has prognostic value for clinical outcomes and may serve as a therapeutic biomarker for breast cancer.

Integrated clinical, pathologic, and genetic data in a racially diverse hereditary breast cancer cohort.

10553 Background: Hereditary breast cancers (HBC) represent 5-10% of breast cancer, predominantly due to pathogenic/likely pathogenic (P/LP) variants in the BRCA1 and BRCA2 genes and other high (e.g., PALB2) and moderate (e.g., ATM and CHEK2) penetrance genes. There remains a paucity of data evaluating the role of germline-somatic interactions and possible confounders on breast cancer outcomes. Furthermore, current knowledge about HBC is predominantly defined in the context of European ancestry. We sought to characterize differences in clinicopathological features and somatic mutations across P/LP variants in a racially diverse HBC cohort. Methods: Among females with breast cancer and a confirmed P/LP variant in BRCA1, BRCA2, PALB2, CHEK2, and/or ATM currently enrolled through existing Vanderbilt-based studies (ICARE: Inherited Cancer Registry and BEST: Black Women: Etiology and Survival of Triple Negative Breast Cancers (TNBC)), we abstracted data from medical records and performed tumor sequencing using the Tempus xT assay (a 596-gene DNA next-generation sequencing panel and whole-transcriptome RNA sequencing). Interim differences in clinicopathological features were analyzed using Pearson’s chi-square test and the frequency of somatic mutations reported by gene. Results: To date, we have data from 91 females with breast cancer (77% White and 23% Black) and a P/LP variant (36 BRCA1, 27 BRCA2, 13 PALB2, 11 CHEK2 and 4 ATM). The median age at diagnosis was 44 (38-50), 85% had localized breast cancer (Stage I-II), and 69% had Grade 3 tumors. Significantly more Black participants were BRCA1 carriers (p = 0.008), with no significant racial differences observed in other genes. There were significant differences in IHC subtype by gene (p &lt; 0.001); with higher frequency of TNBC in BRCA1 carriers (64%) whereas BRCA2, PALB2, CHEK2, and ATM carriers were more likely to have HR+, HER2- breast cancer (67%, 54%, 73%, 75%, respectively). Of the 85% who received chemotherapy, significantly higher rates were observed in BRCA1 carriers (p = 0.02). Most participants opted to proceed with a risk reducing mastectomy (69%) with no difference across genes (p = 0.91). Higher rates of somatic TP53 mutations were observed among BRCA1, BRCA2, PALB2 carriers (89%, 56%, 46%) but not as frequent among ATM (25%) and CHEK2 (9%) carriers. Conclusions: These preliminary results show that among a diverse cohort of females with HBC, BRCA1 mutations were overrepresented among Black females and those with TNBC. BRCA1, BRCA2, and PALB2 carriers had a higher prevalence of somatic TP53 mutations, which are typically associated with more aggressive tumor biology and worse survival outcomes. Current efforts underway include full genomic and transcriptomic analysis, through which we will be able to improve our understanding of breast cancer clinicopathological characteristics and survival outcomes among a diverse cohort of females with HBC.

Tumour-stroma ratio (TSR) in breast cancer: comparison of scoring core biopsies versus resection specimens.

Tumour-stroma ratio (TSR) is an important prognostic and predictive factor in several tumour types. The aim of this study is to determine whether TSR evaluated in breast cancer core biopsies is representative of the whole tumour. Different TSR scoring methods, their reproducibility, and the association of TSR with clinicopathological characteristics were investigated in 178 breast carcinoma core biopsies and corresponding resection specimens. TSR was assessed by two trained scientists on the most representative H&E-stained digitised slides. Patients were treated primarily with surgery between 2010 and 2021 at Semmelweis University, Budapest. Ninety-one percent of the tumours were hormone receptor (HR)-positive (luminal-like). Interobserver agreement was highest using 100 × magnification (κcore = 0.906, κresection specimen = 0.882). The agreement between TSR of core biopsies and resection specimens of the same patients was moderate (κ = 0.514). Differences between the two types of samples were most frequent in cases with TSR scores close to the 50% cut-off point. TSR was strongly correlated with age at diagnosis, pT category, histological type, histological grade, and surrogate molecular subtype. A tendency was identified for more recurrences among stroma-high (SH) tumours (p = 0.07). Significant correlation was detected between the TSR and tumour recurrence in grade 1 HR-positive breast cancer cases (p = 0.03). TSR is easy to determine and reproducible on both core biopsies and in resection specimens and is associated with several clinicopathological characteristics of breast cancer. TSR scored on core biopsies is moderately representative for the whole tumour.

Oncogenic roles of GPR176 in breast cancer: a potential marker of aggressiveness and a potential target of gene therapy.

Belonging to the G-protein coupled receptor 1 family, G protein-coupled receptor 176 (GPR176) is associated with the Gz/Gx G-protein subclass and is capable of decreasing cAMP production. GPR176 expression was detected by qRT-PCR, bioinformatics analysis, Western blot and immunohistochemistry, and compared with clinicopathological characteristics of breast cancer. GPR176-related genes and pathways were subjected to bioinformatic analysis. We also explored the effects of GPR176 on the phenotypes of breast cancer cells. Lower expression of GPR176 mRNA was seen in breast cancer than in normal tissues, but the opposite pattern was found for its protein (p < 0.05). GPR176 mRNA was associated with female sex, low T staging, non-Her-2+ subtypes, non-mutant p53 status in breast cancer (p < 0.05). GPR176 methylation was negatively correlated with its mRNA level and T staging in breast cancer, and was higher in breastcancer than normal tissues (p < 0.05). GPR176 protein expression was positively correlated with older age, small tumor size, and non-luminal-B subtype of breast cancers (p < 0.05). The differential genes of GPR176 were involved in receptor-ligand interaction, RNA maturation, and so forth (p < 0.05). GPR176-related genes were categorized into cell mobility, membrane structure, and so on (p < 0.05). GPR176 knockdown weakened the proliferation, glucose catabolism, anti-apoptosis, anti-pyroptosis, migration, invasion, and epithelial-mesenchymal transition of breast cancer cells. These results indicate that GPR176 might be involved in the tumorigenesis and subsequent progression of breast cancer by deteriorating aggressive phenotypes. It might be utilized as a potential biomarker to indicate the aggressive behaviors and poor prognosis of breast cancer and a potential target of genetic therapy.