Non-triple Negative Breast Cancer Research Articles

Clinical management of a patient with non-triple-negative breast cancer who converts to a triple-negative subtype at recurrence.

The management of patients with advanced breast cancer is becoming increasingly complex compared to the past, mainly due to numerous therapeutic innovations introduced in the current therapeutic scenario. At the time of metastatic disease diagnosis, as indicated by the guidelines, it is important to perform a biopsy of the metastatic sites to optimize choices and expand therapeutic options. Approximately 25-45% of patients who experience a recurrence of the primary tumor lose hormone receptor expression: in this context, solid data comes from a subanalysis of the randomized clinical trial ASCENT, in which the benefit of a treatment with antibody-drug conjugate sacituzumab govitecan is also confirmed in case of non-triple negative breast cancer at diagnosis that subsequently convert to a triple negative subtype. The case reported below is representative of this clinical situation.

Intraoperative radiotherapy: An alternative to whole-breast external beam radiotherapy in the management of highly selective breast cancer: A SEER database analysis.

This study aimed to verify if intraoperative radiotherapy (IORT) can achieve the same survival outcome as whole-breast external beam radiotherapy (EBRT) in early breast cancer after breast-conserving surgery (BCS), and to explore the suitable candidates that can safely receive IORT after BCS. Eligible post-BCS patients who received IORT or EBRT were included in the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2018. Risk factors that affected 5-year overall survival (OS) or breast cancer specific survival (BCSS) were identified by Cox proportional hazards regression analysis. Clinical characteristics, OS, and BCSS were comparatively analyzed between the two treatment modalities. The survival analysis after propensity score matching confirmed that patients who received IORT (n = 2200) had a better 5-year OS than those who received EBRT (n = 2200) (p = 0.015). However, the two groups did not differ significantly in 5-year BCSS (p = 0.381). This feature persisted even after multivariate analyses that took into account numerous clinical characteristics. Although there was no significant difference in BCSS between different subgroups of patients treated with IORT or EBRT, patients over 55 years of age, with T1, N0, non-triple negative breast cancers, hormone receptor-positive, and histologic grade II showed a better OS after receiving IORT. In low-risk, early-stage breast cancer, IORT was not inferior to EBRT considering 5-year BCSS and OS. Considering the equivalent clinical outcome but less radiotoxicity, IORT might be a reasonable alternative to EBRT in highly selective patients undergoing BCS.

A clinical analysis of clinicopathological features and prognostic factors of triple-negative breast cancer

Objectives. The aim of this study was to explore the clinicopathological characteristics, prognostic factors, recurrence patterns and survival analysis of triple negative breast cancer patients compared to non-triple negative breast cancer patients. Materials and methods. The cohort included 420 patients who were diagnosed with breast cancer. The patients were evaluated based on the molecular classification and grouped into TNBC and non-TNBC. Data was explored using SPSS Version 29.0.0.0. Patient and tumor characteristics were studied. Univariate and multivariate Cox Regression was used to analyze prognostic factors. Kaplan Meier method with the log-rank test was performed to observe DFS and OS. Outcomes. The triple negative subtype was observed in 57(13.6%) patients. Patients with TNBC had a greater proportion of grade 3 tumors compared to those with non-TNBC (43.9% vs. 5.5%, p<.001). In the univariate analysis pathological type, tumor size, tumor grade, nodal invasion, lymphovascular invasion, perineural invasion and extra-nodal extension were identified as statistically significant prognostic factors. The mean time to relapse for TNBC was lower 60.0 (95% CI, 37.16 to 82.83) compared to the non-TNBC group with a mean time to relapse of 72.0 months (95% CI, 55.81 to 88.18), nevertheless distributions were not statistically significant X2(1)=1.524, p.217. Mean overall survival was 80.53 months (95% CI, 77.75 to 83.32) in non-TNBC compared to TNBC of 80.04 month (95% CI, 66.76 to 93.33) with a non-statistically significantly Log rank test X2(1)=1.252, p.263. Conclusions. Triple negative breast cancer represents a heterogenous molecular and prognostic group of tumors which needs further clinical trials in order to develop targeted therapies.

Evaluation of the Histone Deacetylase 2 (HDAC-2) Expression in Human Breast Cancer.

Triple negative breast cancer belongs to the most aggressive breast cancer forms. Histone deacetylases (HDACs) constitute a class of enzymes that exhibit a significant role in breast cancer genesis and progression. In this study, we aimed at assessing the clinical importance of HDAC-2 in triple negative breast cancer. A total of 138 breast cancer specimens were examined on an immunohistochemical basis. A statistical analysis was performed in order to examine the association between HDAC-2 and the survival and clinicopathological features of the patients. Increased HDAC-2 expression was observed in every fourth case of triple negative breast cancer with positive HDAC-2 staining, whereas only 12 out of 98 non-triple negative breast cancer samples showed high HDAC-2 expression. HDAC-2 overexpression correlated with prolonged overall survival (OS) and disease-free survival (DFS) in triple negative breast cancer. High HDAC-2 levels in triple negative breast cancer seem to positively influence patient survival, disease stage and recurrence.

Does triple negative breast cancer subtype carry poorer prognosis as compared to non-triple negative breast cancer lesion - A study from a tertiary hospital

Background: The breast cancer (BC), in spite of tremendous advances has continue to remain an enigma. The major change in understanding of BC has taken place after understanding of molecular biology. Aims and Objectives: The objectives are as follows:(1) To categorize the incidence of triple negative BC (TNBC) in hospital based data. (2) To study the prognostic outcomes of TNBC. Materials and Methods: The study was an observational prospective for the period of 18th months, from February 2014 to August 2015, where total 146 cases were selected. The data regarding age, sex, tumor size, stage, grade, nodal status, Nottingham prognostic index (NPI), morphology was noted. All patients underwent immunohistochemistry (IHC) study, maintaining higher quality assurance in the same IHC laboratory. Results: Our study revealed that out of 146 patients, 71 patients are TNBC. The mean age of presentation was 54.06 years in TNBC group. About 69.0% patients presented with Grade III tumor and 74.6% patient presented with NPI ≥5.4 among TNBC. However, 56% patients presented with NPI ≥5.4 among NON TNBC. Most of the morphological variant was IDC (95.8%), 85.9% patients presented with only lymph nodes metastasis among TNBC. Conclusion: The study is tremendously significant from Indian perspective. It proofs that TNBC had the point of diagnosis, seems to be more aggressive. It suggests that Indian BC is likely to be younger at presentation as compared to its Western counterpart.

Deubiquitylase YOD1 regulates CDK1 stability and drives triple-negative breast cancer tumorigenesis

BackgroundAccumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with the initiation and progression of Triple-negative breast cancer (TNBC). The publicly available TCGA database of breast cancer data was used to analyze the OTUD deubiquitinating family members that were correlated with survival of breast cancer and ovarian tumor domain-containing 2 (OTUD-2), or YOD1 was identified. The aim of present study was to assess YOD1 expression and function in human TNBC and then explored the underlying molecular events.MethodsWe detected the expression of YOD1 in 32 TNBC and 44 NTNBC samples by qRT-PCR, Western blot and immunohistochemistry. Manipulation of YOD1 expression was assessed in vitro and in vivo for TNBC cell proliferation, migration, invasion, cell-cycle and drug resistance, using colony formation assay, transwell assay, CCK8 assay, TUNEL assay, flow cytometric analysis and xenograft tumor assay. Next, proteomic analysis, Western blot, proximity ligation assay, Immunoprecipitation, and Immunofluorescence were conducted to assess downstream targets.ResultsIt was found that YOD1 was significantly upregulated in TNBC tissues compared with non-triple-negative breast cancer (NTNBC), which was positively correlated with poor survival in TNBC patients. Knockdown of YOD1 effectively inhibited TNBC cell migration, proliferation, cell cycle and resistance to cisplatin and paclitaxel. Mechanistically, YOD1 promoted TNBC progression in a manner dependent on its catalytic activity through binding with CDK1, leading to de-polyubiquitylation of CDK1 and upregulation of CDK1 expression. In addition, YOD1 overexpression was found to be correlated with CDK1 overexpression in human TNBC specimens. Finally, in vivo study demonstrated that YOD1 knockdown or YOD1 inhibitor could inhibit CDK1 expression and suppress the growth and metastasis of TNBC tumors.ConclusionOur study highlights that YOD1 functions as an oncogene in TNBC via binding to CDK1 and mediated its stability and oncogenic activity. Interfering with YOD1 expression or YOD1 inhibitor could suppress TNBC cells in vitro and in vivo, suggesting that YOD1 may prove to be a promising therapeutic target for TNBC.

Clinicopathological and prognostic characteristic features of triple negative and nontriple negative breast cancer at a tertiary care hospital.

Carcinoma breast is a complex disease having diverse clinical, histopathological, and immunohistochemical features. Basing on estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2) status, these tumors are divided into triple-negative breast cancers (TNBC) where tumor cells are negative for all three receptors and nontriple negative breast cancer (non-TNBC) where tumor cells are positive for one or two or all. The clinicopathological and characteristic prognostic features are highlighted here. The aim of this study is to evaluate the clinicopathological and prognostic features of TNBC and non-TNBC cases diagnosed in our hospital setting. Single institution, retrospective study conducted over 7 and half years. Histopathologically confirmed breast cancer cases with ER, PR, and HER2 receptor assessment were categorized into TNBC and non-TNBC. Detailed study on clinicopathological and prognostic features including pathological prognostic stage as per 8th AJCC was done in cases who underwent modified radical mastectomy. Data were analyzed in percentage and presented in tables and charts. The present study included 794 cases consisting of 253, 31.9% TNBC and 541, 68.1% non-TNBC cases. The mean age of TNBC and non-TNBC cases was 50.4 years and 51.7 years, respectively. Coagulative necrosis, lymphovascular invasion, lymph nodal metastasis, higher histopathological tumor grade, and NPI were observed in higher percentage of TNBC cases, i.e., 19 (10.9%), 21 (11.6%), 105 (57.7%), 127 (69.8%), and 149 (81.9%) cases, respectively, than non-TNBC seen in 18 (6.6%), 24 (8.8%), 135 (49.6%), 165 (60.7%), and 194 (71.3%) cases, respectively. Further, 25 (13.7%) TNBC and 1 (0.4%) non-TNBC case were upstaged, whereas 130 (47.8%) non-TNBC and 2 (1.1%) TNBC cases were downstaged by the pathological prognostic stage. TNBC is more aggressive having a poor prognosis than non-TNBC.

Abstract P2-11-35: A tight junctional scaffold protein MUPP1/MPDZ and its docking proteins, angiomotins in breast cancer

Abstract A tight junctional scaffold protein MUPP1/MPDZ and its docking proteins, angiomotins in breast cancer Han Gao1, Fiona Ruge1, Lin Ye1, Jane Lane1, Eleri Davies2, Wen G. Jiang1, Tracey A. Martin1 1Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK 2Wales Breast Centre, University Llandough Hospital, Cardiff CF64 2XX, UK Introduction. MUPP1 (Multiple PDZ Domain Crumbs Cell Polarity Complex Component) or MPDZ is a scaffold protein with multiple PDZ domains, critical for multiple protein docking and protein-protein interactions in cells. MUPP1 is particularly interesting as it offers docking sites for a number of tight junction (TJ) proteins and proteins known to regulate cell junction and motility, including angiomotin (AMOT) and angiomotin-like proteins, the latter being important in regulating cell migration of endothelial cells and an important member in TJ protein complexes. The MUPP1 protein complex at cell junctions also includes CAR/CXADR (coxsackie adenovirus receptor) and members of the ERM (Moesin-Ezrin-Radixin) protein family. It was proposed that the junctional-related MUPP1 docking protein complex may collectively have a role in the development and progression of cancer including breast cancer. The present study examined the profile and integrated expression of these MUPP1 docking molecules in relationship with the outcome, clinical and pathological factors of breast cancer. Methods. Using the datasets of an existing breast cancer cohort at Cardiff, we visited the expression profile of the MUPP1/MPDZ docking molecules including MUPP1, four members of the ERM family, including ezrin, moesin, radixin and EHM2 (also known as NF2) and CAR/CXADR (coxsackie adenovirus receptor). The profile and integrated expression of the profile were analysed against clinical, pathological and outcome factors and also the hormone receptor status of breast cancers. Results. MUPP1 is a weakly linked to the disease progression, so as angiomotin, angiomotin-like1 and angiomotin-like2. Alone, only EHM2 showed significance in linking with the survival of the patient’s OS (p=0.38), neither of the remaining MUPP1 complex molecules, including MUPP1, AMOT, AMOTL1, AMOTL2, ezrin, moesin and radixin was able to offer a significant predictive value for the survival of the patients. However, it was found that MUPP1 has a significant correlation with AMOTs, EHM2 and ezrin. When these significantly correlated molecules were integrated in the analysis, the integrated expression pattern showed a highly significant value in evaluating the overall survival (p=0.003) and disease-free survival (p=0.007). Both of these predictive powers are independent in a multivariate analyses including the clinical and hormone receptors for OS (p=0.022, Hazard Ratio (HR)=1.352 95%CI (1.044-1.752)) and RFS (p=0.023, HR=1.241 (95% CI. 1.031-1.498)). It was interesting to note that the link between the expression pattern and OS was more prominent in ER negative (p=0.018) than in ER positive tumours (p=0.177). The same was observed with disease free survival for ER negative (p=0.011) compared with ER positive (p=0.462) tumours. Non-triple negative breast cancer had shown a similar sensitivity compared with triple negative breast cancer. Discussion. MUPP1, a PDZ domain containing docking protein closed linked with TJ structure, forms an interesting expression profile with its docking molecules including angiomotins and EHM2 that allows evaluation of disease progress and clinical outcome of the patients with breast cancer. Citation Format: Han Gao, Fiona Ruge, Lin Ye, Jane Lane, Eleri Davies, Wen G. Jiang, Tracey A. Martin. A tight junctional scaffold protein MUPP1/MPDZ and its docking proteins, angiomotins in breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-35.

Abstract P3-03-19: Real-world data of clinical characteristics, risk factors and outcomes of Chilean triple-negative breast cancer patients

Abstract Background: triple-negative breast cancer (TNBC) is associated with hereditary and environmental risk factors plus an overall worse prognosis compared to other Breast Cancer (BC) subtypes. While TNBC risk factors, prevalence, clinical characteristics and prognosis may vary throughout different populations, limited data on Latin American patients forces clinical decisions to be based predominantly on data coming from non-Hispanic women. To obtain local epidemiological information, regarding risk factors and clinical outcomes, we analysed the largest Chilean BC registry. Methods: we conducted a retrospective population-cohort study involving females with any stage TNBC, treated at a community hospital (mid-low income) and at an academic private hospital (high income), between the years 2010 and 2021. Risk factors, reason for consultation, clinical and pathological characteristics and prognosis were separately analysed for both TNBC and non-TNBC subgroups. Univariate and multivariate analyses were performed to identify prognostic factors for survival on TNBC patients. Results: From 5,806 patients, 647 (11.2%) were identified as TNBC. Compared to non-TNBC patients, women were younger (median age 55.2 vs. 57.2, p=0.0001), with 15.8% of TNBC patients having been diagnosed before the age of 40 compared to 9.6% in non-TNBC (p= 0.0001). TNBC had a significantly lower screen-detected cancer rate (14.5% vs. 31.6% p= 0.0001) and worse stage at diagnosis. No differences were seen between patients seen at a community hospital and private centre, for both TNBC rate and stage. Other risk factors such as parity, age at first gestation, menarche, hormone therapy replacement and obesity showed no significant differences between TNBC and no-TNBC patients (table 1). With a median follow up of 57 months, 5-year overall survival (OS) and BC specific death were significantly shorter for TNBC compared to non-TNBC (76.4% vs 88.1% and 78.9% vs 91.2%, respectively; p=0.0001) (table 2). In the multivariate analysis, TN subtype (HR=2.3, p=0.0001), stage (HR=2.05 for stage II vs stage I, HR=7.04 for stage III vs. stage I, p=0.0001), lower income (HR= 1.64, p=0.0001), and non-screened detected BC (HR=1.32, p=0.03) were all associated with worse overall survival (table 3). Conclusion: This is the first study focusing on TNBC characteristics in Chilean BC patients and to our knowledge, the largest performed in a Latin American population. We identified a lower proportion of TNBC patients when compared with data reported from other LA groups and worldwide, a very low screen detected cancer rate and as expected significantly lower TNBC survival rate compared to non-TNBC women. While TNBC patients were younger compared to the non-TNBC group, this age difference was marginal compared to other reported studies. Community hospital patients (with mid-low income) were associated with lower survival rates for both all-cause mortality and BC specific survival, regardless of a similar stage distribution at diagnosis. Reflecting an underlying interaction between social and biological factors that needs to be addressed. Table 1. Patient characteristics: Triple-negative versus noN-triple negative breast cancer BMI: Body mass index; FH: Family history * Difference is statistically significant. Table 2. Survival comparison in triple-negative versus non-triple negative breast cancer * Difference is statistically significant. Table 3. Cox Regression Multivariate analysis * Difference is statistically significant. Citation Format: Benjamin Walbaum, FRANCISCO ACEVEDO, Catherine Bauerle, Mauricio Camus, Manuel Manzor, Raul Martinez, Paulina Veglia, Marisel Navarro, Constanza Guerra, Francisco Dominguez, Tomas Merino, Lidia Medina, CÉSAR SÁNCHEZ. Real-world data of clinical characteristics, risk factors and outcomes of Chilean triple-negative breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-19.

Abstract P6-14-16: Claudin-9 and its subcoat anchorage proteins ZO-1 and ZO-3 in breast cancer, the clinical and therapeutic significance

Abstract Introduction. Claudin-9 (CLDN9), a member of the claudin protein family, is thought to play a role in the control of tight junctions (TJ) in various cell types. CLDN9 protein needs intracellular subcoat proteins, primarily the Zonula Occluden (ZO)-1 and ZO-3 to anchor to the cytoskeleton in order to form TJ with other proteins, including occludin. In the body, CLDN9 is highly expressed in endocrine tissues but is relatively low in mammary tissues. The role of CLDN9 is not well understood in cancer. In the present study, we have for the first time examined the pattern of CLDN9 expression at protein and transcript levels in breast cancer and explored its clinical and therapeutic implications. Methods. CLDN9 protein and CLDN9 transcript in fresh frozen human mammary tissues were evaluated by immunohistochemistry and quantitative transcript analyses and, together with the ZO family members and occludin in our database, correlated with clinical indicators. Assessment of expression in a range of cell lines was also determined. The levels of CLDN9 transcript, was also assessed against the therapeutic responses of the patients to chemotherapies by using a dataset from TCGA database. Results. Breast tumour tissues had high levels of CLDN9 transcript in tumours versus normal tissues. However, high grade breast tumours had significantly lower levels than low grade (p=0.02 and p=0.003, grade-2 and 3 vs grade-1 respectively). Patients with metastasis also had significantly lower levels than those without (p=0.0075). Patients who died of breast cancer had higher levels of the transcript than those who survived, although this was not significant. CLDN9 expression was significantly correlated with ZO-1 (r=0.20, p< 0.001) and ZO-3 (r=0.179, p< 0.01), but not ZO-2 in our cohort. There was significant correlation with another key TJ molecule, occludin (r=0.236, p=0.11). CLDN9, together with ZO-1 and ZO-3 significantly linked to the survival of patients (1444.6 months for the low expressing group versus 1138.2 months for the high expression group, p=0.013). The expression profile of the CLDN9/ZO1/ZO3 complex also indicated potential as an independent prognostic indicator (p=0.004, HR=2.033). The prognostic value was highly applicable to non-triple negative breast cancer patients. CLDN9 transcript also appeared to have a significant impact on treatment responses; patients who were sensitive to chemotherapies had a significantly lower levels of CLDN9 transcript than those who were resistant to treatment (p< 0.000001). In human cell lines, expression levels of CLDN-9 in ER (+) breast cancer cell lines, MDAMB361, MCF7 and BT474 were high; in a ER(-) breast cancer cell line MDAMB231, the expression level of CLDN-9 was lower. Conclusion. In conclusion, CLDN9 expression was differentially expressed in human breast cancer cells lines and appeared to reflect changes in ER status. It was apparent from levels of CLDN9 in a breast cancer cohort that expression was associated with grade and metastatic disease. Of significant notice was the finding that expression of CLDN9 in an expression profile with ZO1 and ZO3 has potential as a prognostic indicator, particularly in non-triple negative patients and in those who are chemotherapy resistant. Citation Format: Xinguo Zhuang, Wen G. Jiang, Eleri Davies, Bing Xu, Tracey A. Martin. Claudin-9 and its subcoat anchorage proteins ZO-1 and ZO-3 in breast cancer, the clinical and therapeutic significance [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-14-16.

Long Noncoding RNA LINC01614 is a Diagnostic and Prognostic Marker for Breast Cancer.

The long intergenic non-coding RNA 01614 (LINC01614) is aberrantly expressed in various malignancies, suggesting its role in oncogenesis. However, it has not been well studied in breast cancer. The cancer genome atlas databases (TCGA) and public database of breast cancer gene-expression miner (bc-GenExMiner) were utilized to analyze the prognostic role of LINC01614 in breast cancer. Kaplan-Meier, and Cox regression analyses were conducted for survival analysis. Nomograms were built to predict survival. We used deconvolution-based methods, such as TIMER (Tumor Immune Estimation Resource) and CIBERSORT (cell-type identification by estimating relative subsets of RNA transcripts), to explore the relationship between LINC01614 and immune cell characteristics. The very abnormal expression of LINC01614 was found in 14 types of malignancy, including breast cancer. The LINC01614 was significantly overexpressed in human epidermal growth factor receptor 2 (HER2)+, estrogen receptor (ER)+, progesterone receptor (PR)+, and non-triple negative breast cancer (non-TNBC). According to survival analysis, the higher expression of LINC01614 was related with poor survival. The co-expressed genes analysis exhibited that LINC01614 was closely associated with the collagen-associated process and phosphoinositide 3-kinases-protein kinase B (PI3K-Akt) signaling pathway. Moreover, this study has explored the association among LINC01614 expression, tumor-infiltrating immune cells, and the efficacy of chemotherapeutics. Our data reveal the expression pattern of LINC01614 in breast carcinoma with different molecular subtypes. The results also indicated that the LINC01614 could be a novel diagnostic and prognostic marker for breast carcinoma.

Combined targeting of KRT23 and NCCRP1 as a potential novel therapeutic approach for the treatment of triple-negative breast cancer.

Breast cancers characterized by triple-negative status tend to be more malignant and have a poorer prognosis. A risk model for predicting breast cancer risk should be developed. We obtained gene expression and clinical characteristics data using the Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) database. Differential gene screening between patients with triple-negative breast cancer (TNBC) and non-triple-negative breast cancers (NTNBC) was performed according to the "edgeR" filter criteria. Univariate and multivariate Cox regression analyses were used to construct a risk model and identify prognosis-related genes. XCELL, TIMER, EPIC, QUANTISEQ, MCPCOUNTER, EPIC, CIBERSORT-ABS, and CIBERSORT software programs were used to determine the extent of tumor immune cell infiltration. To evaluate the clinical responses to breast cancer treatment, the half maximal inhibitory concentration (IC50s) of common chemotherapeutics were calculated using "pRRophetic" and "ggplot2". Cell proliferation was assayed using cell counting kit-8 (CCK8) and 5-Ethynyl-2'-deoxyuridine (EdU) Cell Proliferation Kit. A dual-luciferase reporter assay confirmed the gene regulatory relationship of sex determining region Y-box 10 (SOX10). An assessment model was established for Keratin23 (KRT23) and non-specific cytotoxic cell receptor 1 (NCCRP1) using the univariate and multivariate Cox regression analyses. In addition, high expression levels of KRT23 and NCCRP1 indicated high proliferation and poor prognosis. We also found that the gene expression patterns of multiple genes were significantly more predictive of risks and have a higher level of consistency when assessing risk. In vitro experiments showed that the expressions of KRT23 and NCCRP1 were increased in TNBCs and promoted cell proliferation. Mechanically, the dual-luciferase reporter assay confirmed that SOX10 regulated the expressions of KRT23 and NCCRP1. The risk score model revealed a close relationship between the expressions of KRT23 and NCCRP1, the tumor immune microenvironment, and chemotherapeutics. In conclusion, we constructed a risk assessment model to predict the risk of TNBC patients, which acted as a potential predictor for chemosensitivity.

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.

Breast Cancer Subtypes Classification with Hybrid Machine Learning Model.

Breast cancer is the most prevailing heterogeneous disease among females characterized with distinct molecular subtypes and varied clinicopathological features. With the emergence of various artificial intelligence techniques especially machine learning, the breast cancer research has attained new heights in cancer detection and prognosis. Recent development in computer driven diagnostic system has enabled the clinicians to improve the accuracy in detecting various types of breast tumors. Our study is to develop a computer driven diagnostic system which will enable the clinicians to improve the accuracy in detecting various types of breast tumors. In this article, we proposed a breast cancer classification model based on the hybridization of machine learning approaches for classifying triple-negative breast cancer and non-triple negative breast cancer patients with clinicopathological features collected from multiple tertiary care hospitals/centers. The results of genetic algorithm and support vector machine (GA-SVM) hybrid model was compared with classics feature selection SVM hybrid models like support vector machine-recursive feature elimination (SVM-RFE), LASSO-SVM, Grid-SVM, and linear SVM. The classification results obtained from GA-SVM hybrid model outperformed the other compared models when applied on two distinct hospital-based datasets of patients investigated with breast cancer in North West of African subcontinent. To validate the predictive model accuracy, 10-fold cross-validation method was applied on all models with the same multicentered datasets. The model performance was evaluated with well-known metrics like mean squared error, logarithmic loss, F1-score, area under the ROC curve, and the precision-recall curve. The hybrid machine learning model can be employed for breast cancer subtypes classification that could help the medical practitioners in better treatment planning and disease outcome.

Expression characteristics of the yes-associated protein in breast cancer: A meta-analysis.

Background:The yes-associated protein (YAP) gene plays an important role in many malignant tumors, but its clinical significance in breast cancer remains unclear. This study aimed to explore the significance of YAP expression in breast cancer using meta-analysis.Methods:Seven databases will be searched to collect the case–control studies published on the association between YAP expression and clinical pathogenic features in breast cancer until December 2021: PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Chinese Scientific Journal Database, Wan Fang Database, and the Chinese Biomedical Literature Database. To perform meta-analysis, STATA 14.0 and RevMan5 software were used with odds ratio (OR) and 95% confidence interval (95% CI) as the effect index, and publication bias and sensitivity analysis were subsequently tested.Results:Form a total of 10 articles used in this study, 8 studies consisted of nontriple negative breast cancer (non-TNBC) and the other 2 of TNBC. Meta-analysis indicated a positive expression rate of YAP in non-TNBC tissues that was lower than in normal breast tissue (OR = 0.15, 95% CI = 0.10–0.21, P < .001). In contrast, the positive rate of YAP expression in TNBC was significantly higher than that in normal breast tissue (OR = 18.23, 95% CI = 8.20–40.52, P < .001). Furthermore, the positive expression rate was higher in the patients with lymph node metastasis, higher tumor node metastasis stage and histologic grade, and larger diameter in TNBC. However, there was no statistical difference in the positive expression rate of YAP between non-TNBC patients and lymph node metastasis, tumor node metastasis stage, histologic grade, and tumor size.Conclusions:YAP may participate in the occurrence and development of non-TNBC as a tumor suppressor gene; however, it may also be a carcinogenic factor in TNBC and may be a potential therapeutic target for TNBC.

DCE-MRI Performance in Triple Negative Breast Cancers: Comparison with Non-Triple Negative Breast Cancers.

Triple negative breast cancers are considered the worst prognosis in breast cancer. Dynamic contrast enhanced magnetic resonance imaging has been widely used in the diagnosis of breast cancer since it is more sensitive to breast cancer. However, few studies report the MRI characteristics of triple negative breast cancers. The study aimed to evaluate the imaging finding in triple negative breast cancers compared with non-TNBC and attempt to predict it. 223 patients with a preoperative diagnosis of breast cancer were enrolled in the study. Dynamic contrast enhanced magnetic resonance imaging was performed before being diagnosed with breast cancer, and histopathological assessment was confirmed after biopsy or operation. The patients were divided into 2 groups based on immunohistochemistry, namely the triple negative breast cancers or non-triple negative breast cancers. The 2 groups demonstrated significant differences regarding the tumor size, margin, outline, burr sign, enhancement, inverted nipple(P<0.05). A multivariate logistic regression analysis was performed to further validate the association of these features, however, only margin [odds ratio (OR), 0.038; 95% confidence interval (CI), 0.014-0.100; <0.001], outline [odds ratio (OR), 0.039; 95% confidence interval (CI), 0.008-0.200; <0.001], burr sign [odds ratio (OR), 2.786; 95% confidence interval (CI), 1.225-6.333; 0.014], and enhancement [odds ratio (OR), 0.131; 95% confidence interval (CI), 0.037-0.457; P=0.001] were associated with TNBC. The results indicated that the specific dynamic contrast enhanced magnetic resonance imaging features can predict pathological results, with a consequent prognostic value.

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.

Potential prognostic value of the lymph node ratio and its correlation with circulating sex hormone concentration in pathological T1/2 breast cancer patients: a retrospective study.

BackgroundThe lymph node ratio (LNR) is an additional informative factor complementing anatomic TNM staging in breast cancer patients. The aim of this study was to evaluate the role of LNR in the cancer-specific and overall survival (OS) in a cohort of pT1/2 breast cancer patients and examine its correlation with circulating sex hormone concentrations in postmenopausal cases of the cohort from eastern China islands.MethodsClinical and pathological characteristics, preoperational sex hormone and tumor markers concentrations, and breast cancer-specific survival (BCSS) and OS were analyzed retrospectively in 732 pathological T1/2 breast cancer patients.ResultsThe LNR was calculated, and the cut-off value was defined as 0.042 by receiver operative characteristic (ROC) curve according to the patient’s mortalities. Patients with LNR ≥0.042 exhibited worse BCSS and OS than others (P<0.001) in pT1/2 breast cancer. Among patients with non-triple negative breast cancer (TNBC) and TNBC subtypes, the LNR ≥0.042 group also exhibited worse BCSS and OS than the LNR <0.042 group (P=0.003, 0.001, and P=0.032, 0.001, respectively). In univariate analysis, unfavorable BCSS and OS were both related with LNR ≥0.042 (P=0.001, <0.001). However multivariate analysis demonstrated TNBC subtypes were independent predictor for BCSS and OS [hazard ratio (HR) =1.449, 95% CI: 1.097–1.914, P=0.009; HR =1.365, 95% CI: 1.093–1.705, P=0.006, respectively]. Notably, Pearson or spearman correlation analysis revealed follicle-stimulating hormone (FSH) and, luteinizing hormone (LH) levels were significantly negatively associated with the LNR (P=0.007, 0.011, respectively) in postmenopausal cases, whereas CA153, CA125 and CEA were positively correlated with it (P<0.001, <0.001, 0.001, respectively) in all cases.ConclusionsAmong pT1/2 breast cancer patients from eastern China islands, the LNR is a predictive prognosis factor; a higher LNR seems to correlate with a worse survival outcome both overall and in the subgroups. Strikingly, the current results reveal that serum FSH and LH level inversely associated with axillary node invasion in postmenopausal cases, whereas tumor markers directly related with it. The LNR is an informative factor complementing TNM staging.

NF-?? Pathway is a key modulator of BRCA-1 mutation induced chemo-Resistance in triple negative breast cancer

Triple-negative breast cancer (TNBC) is considered to be more aggressive and have a poorer prognosis than other types of breast cancer. The specific gene expression pattern between TNBC and other non-triple negative breast cancer (nTNBC) is yet to be resolved. Hence the present study was aimed to study the BRCA-1 status and measure the important tumor markers mRNA expression in peripheral blood samples of TNBC and other nTNBC subjects and compared with control subjects. EDTA blood samples were obtained from 25 CA (cancer) breast patients and 25 controls for DNA and RNA isolation. PCR-RFLP analysis was performed to check the BRCA-1 mutation in all the samples. Results showed that BRCA-1 mutation was present in all TNBC patients. Subsequently, quantitative RT-PCR was performed to detect the relative mRNA expression of NF-κβ, VEGFA, Caspase-3, and ERBB2 gene transcripts. Results showed that the transcript levels of NF-κβ, VEGFA, and ERBB2 were significantly up regulated in TNBC (p=0.0001) when compared to nTNBC and control. Transcript levels of caspase-3 were significantly down regulated (p=0.0001) in TNBC compared to nTNBC and control subjects. In conclusion, BRCA-1 mutation in TNBC patients confers resistance to chemotherapy activated by NF-κβ pathway and activation of adhesion and angiogenesis was associated with aggressive and poor prognosis in TNBC patients. Keywords: TNBC, Breast cancer, Cytokines, Tumour and gene expression.

PROGNOSTIC FACTORS AND SURVIVAL IN TRIPLE NEGATIVE AND NON-TRIPLE NEGATIVE BREAST CANCER: EXPERIENCE OF A TERTIARY CARE CANCER CENTER IN ODISHA.

&#x0D; Background: Because of its high-risk biological features and lack of effective treatment options, triple-negative breast cancer (TNBC) has received greater clinical and experimental interest.&#x0D; &#x0D; &#x0D; Aim and objectives: The aim of this study was to compare and analyze the clinicopathological features, recurrence, metastasis, and prognosis of patients with TNBC and non-triple negative breast cancer (non-TNBC).&#x0D; &#x0D; &#x0D; Material and methods: This single hospital-based retrospective study was conducted on patients who were histopathologically diagnosed with breast cancer and subsequently treated from 2017 to 2018 at the Acharya Harihar Postgraduate Institute of Cancer. The clinical features and prognosis of TNBC and non-TNBC were compared.&#x0D; &#x0D; &#x0D; Results: This study comprised a total of 111 patients, with 36 (32.43%) being TNBC and 75 (67.56%) being non-TNBC. TNBC has 22 patients under the age of 40 (61.1%). Grade III tumors were seen in 47% of TNBC patients and 21% of non-TNBC patients (p-value = 0.05). The disease free survival (DFS) was determined to be 58 % for TNBC and 82% for non-TNBC groups, respectively (p-value = 0.05). These two groups had an overall survival rate (OS) of 72% and 92%, respectively (p-value = 0.05).&#x0D; &#x0D; &#x0D; Conclusion: When compared to non-TNBC, TNBC was related to high-grade malignancies, worse disease-free survival , and overall survival (OS) rates. Understanding the molecular features of TNBC, clarifying its mechanism at the molecular level, interpreting the gene expression profiles of TNBC, and studying and creating new therapeutic targets should be the focus of future research. To enhance the prognosis of TNBC patients, try to find a focused and effective therapy.&#x0D; &#x0D; Keywords:&#x0D; Breast cancer; survival; triple-negative breast cancer.