Prognosis Of Breast Carcinoma Research Articles

Vascular Endothelial Growth Factor Expression by Immunohistochemistry as a Possible Indicator of Prognosis in Invasive Breast Carcinoma of No Special Type

Context: Angiogenesis, the formation of new blood vessels from preexisting vascular network, is essential for tumor growth and spread. Vascular endothelial growth factor (VEGF) is a potent angiogenic growth factor. Aims: To assess the expression of VEGF in invasive carcinoma of no special type and its correlation with all the known prognostic factors of breast carcinoma. Settings and Design: Descriptive. Materials and Methods: Mastectomy specimens were studied noting the clinical details. The formalin-fixed tissues were subjected to routine processing and hematoxylin and eosin sections and studied extensively for all the histological prognostic factors. Representative sections from each case with the tumor were subjected to immunohistochemistry (IHC) staining with VEGF, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/neu) antibodies. Statistical Analysis Used: Descriptive statistics, Chi-square tests, contingency table analysis using SPSS for Windows. Results: One hundred and twelve cases of invasive carcinoma of special type were studied to evaluate various clinicopathological parameters. The association of VEGF with clinicopathological parameters and all the known prognostic factors was studied to note its significance. VEGF overexpression was observed in 69% of the cases. It was noted that larger tumor size, higher histological grade, lymphovascular invasion, nodal involvement, tumor necrosis, high microvessel density, ER negativity, PR negativity, and HER2/neu positivity had a significant statistical association with VEGF overexpression. Conclusions: We conclude that incorporating VEGF as a biomarker along with the known factors into a prognostic index will not only help predict clinical outcome more accurately, but also determines the patient who can be benefited with combinational therapy including anti-VEGF factors.

Association of Serum Vitamin D with Risk of Breast Carcinoma: An Observational Case-control Study from Western Maharashtra, India

Introduction: Breast carcinoma is one of the most prevalent types of carcinoma and the leading cause of death among all carcinomas. Recently, vitamin D deficiency has been reported as a risk factor for breast carcinoma. Vitamin D, as an anticarcinoma agent, prevents cellular differentiation, stimulates cell death, reduces angiogenesis, tumour progression, and metastasis. Aim: To investigate the relationship between vitamin D deficiency and the risk of breast carcinoma. Materials and Methods: An observational study was conducted at the Armed Forces Medical College, Pune, Maharashtra, India, between November 2018 and October 2020. A total of 57 cases diagnosed with breast carcinoma and 57 healthy controls were analysed. Physical and reproductive health parameters were compared, along with vitamin D status using student’s t-test and Mann-Whitney U test. Logistic regression was used to assess the risk of breast carcinoma. Results: Out of 114 women, 57 were cases and 57 were controls with a mean age of 52 vs 48 years. The mean value of serum vitamin D levels was significantly lower (19.45 vs 27.91 ng/mL, p<0.001) than controls. The percentage of serum Vitamin D deficiency was significantly higher in cases (28 (49.1%) vs 12 (21.1%), p<0.001) compared to controls. Vitamin D concentration <20 ng/mL was significantly associated with a higher risk of breast carcinoma (OR 10.8, 95% CI 3.1-37.6). Multiparity ≥3 was associated with a decreased risk of breast carcinoma (OR 2.250, 95% CI 0.599-8.447) compared to parity ≤2 (OR 3.241, 95% CI 0.916-11.466). In luminal A and triplenegative subtypes, severe vitamin D deficiency (<20 ng/mL) was observed (p=0.045) compared to other subtypes. Conclusion: The present study findings showed that women diagnosed with breast carcinoma had low vitamin D levels, which were linked to an increased risk and prognosis of breast carcinoma. Furthermore, multiparity lowers the risk of breast carcinoma.

Comparison of the prognosis of medullary breast carcinoma and invasive ductal carcinoma: a SEER-based study.

Medullary breast carcinoma (MBC) is a rare type of breast cancer. Our study aimed to compare the differences in clinical characteristics and prognosis between MBC and invasive ductal carcinoma (IDC), and to further develop and validate nomograms to predict overall survival (OS) and cancer-specific survival (CSS) in MBC patients. A total of 179,613 patients from the Surveillance, Epidemiology and End Results (SEER) database from 2010 to 2015, including 596 MBC patients, were analyzed using the Kaplan-Meier method and propensity score matching (PSM) to compare patients' OS and CSS. Cox proportional hazard regression model was used to determine independent prognostic factors for OS and CSS in MBC patients. Nomograms were constructed based on Cox regression analysis whereas receiver operating characteristic (ROC) curves and calibration curves were used to evaluate the predictive accuracy. There were significant differences in the clinical characteristics between MBC and IDC. According to the logrank test, MBC had better OS and CSS than IDC before and after PSM. Cox multivariate analysis showed that age, race, tumor size, lymph node (LN), and radiation therapy were independent prognostic factors for OS, whereas age, tumor size, American Joint Committee on Cancer (AJCC) stage, laterality, type of surgery, and chemotherapy were independent prognostic factors for CSS. Nomograms of OS and CSS were constructed based on independent prognostic factors. MBC had better OS and CSS than IDC. Nomograms based on clinicopathological features were sufficiently accurate in predicting the OS and CSS for MBC patients, which can effectively predict the survival risk of MBC patients and guide clinicians to provide more effective treatment measures.

Construction and validation of a transient receptor potential-related long noncoding RNA signature for prognosis prediction in breast cancer patients.

Breast cancer (BC) is the most commonly diagnosed malignancy in women around the world. Accumulating evidence suggests that transient receptor potential (TRP) channels play a significant role in tumor progression and immune cell infiltration. Hence, we conducted the study to investigate the correlation between TRP-associated lncRNAs and the prognosis of breast carcinoma. In the current study, 33 TRP-associated genes were selected from a review published by Amrita Samanta et al, and the TRP-related lncRNAs were identified by Pearson analysis. Based on the sum of the expression levels of 12 lncRNAs provided by the Cancer Genome Atlas (TCGA), a TRP-associated lncRNA signature was established by using Cox regression analysis. According to the median value of the risk score in the training set, BC patients were separated into high- and low-risk groups. Subsequently, functional enrichment analysis was conducted on the differential expression genes (DEGs) between different risk groups. The Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression (ESTIMATE) Score was calculated by ESTIMATE, and the immune cell infiltration was evaluated by ssGSEA. Finally, the immune checkpoint gene expression levels, microsatellite instability (MSI), and immunophenoscore (IPS) were further assessed. The high-risk groups exhibited lower survival rates, while the low-risk groups showed higher survival rates. As a result, the DEGs between different risk groups were highly enriched in immune cell activation and immunoregulation. Besides, the ESTIMATE scores of patients in low-risk groups were higher than those in high-risk groups. The infiltration levels of several immune cells were remarkably elevated in low-risk groups, and various immune signatures were activated with a decreased risk score. Eventually, the TRP-associated lncRNA signature was confirmed with a highly potential ability to evaluate the immunotherapy response in breast carcinoma patients. The outcomes of the current study indicated that the 12-TRP-associated-lncRNA risk model was an independent prognostic risk factor for BC patients. This risk model could be closely related to the tumor immune microenvironment in BC. Our findings will provide new insights for future immunotherapy for BC treatment.

Epithelial Carcinomas Arising within Phyllodes Tumours of the Breast: A Review of Their Pathological Characteristics.

Epithelial proliferation is a common feature of phyllodes tumours (PTs), but epithelial malignancy is rare. This review seeks to further our understanding of epithelial malignancy within PTs by analysing their histopathological characteristics in previously reported cases and providing an overview of studies on their pathological features. PubMed and DeepDyve were searched for case reports, case series, and literature reviews of in situ and invasive carcinoma within PTs. Only cases where the carcinoma was within the PT were included. Cases of synchronous carcinoma in the ipsilateral or contralateral breast were excluded. Ninety-eight cases of in situ or invasive carcinoma within a PT were identified. Across the grades of PTs, there was a similar proportion of invasive carcinomas compared to in situ lesions. Malignant PT correlates with a higher likelihood of epithelial malignancy, and molecular studies support a possible causal pathophysiological relationship. This higher likelihood may suggest interactions between malignant stroma and the transforming epithelium that could potentially play a significant role in the phenomenon, which remains to be elucidated. Encasement within a PT likely improves the prognosis of breast carcinoma due to earlier detection. The presence of carcinoma within a malignant PT has uncertain prognostic implications. Thorough sampling of all PTs is recommended for appropriate prognostication and management.

Multimodal Imaging Features and Prognosis of Metaplastic Breast Carcinoma

Metaplastic breast carcinoma (MBC) is an infrequent malignancy with an unfavorable prognosis, and there is a paucity of research on the multimodal imaging features of MBC. This study aimed to provide a comprehensive analysis of the multimodal imaging features, clinicopathological characteristics, and prognosis of MBC. A total of 36 patients with histologically confirmed MBC from 2012 to 2021 were included in the study. We analyzed the pre-treatment multimodal imaging features, including mammography, ultrasonography (US), and magnetic resonance imaging (MRI), as well as clinicopathology and prognosis of MBC. Follow-up data included local recurrence, distant metastasis, and overall survival (OS) rate. MBC patients had a median age of 51 years at diagnosis. The most common histologic subtype was squamous cell carcinoma, with 86.1% of MBC being histological grade 3 and triple negative. The most common mammographic findings were irregular shape, non-calcification, and high density. The predominant US findings included irregular shape, parallel orientation, posterior acoustic enhancement, and hypoecho. On MRI, most masses exhibited irregular shape, spiculate margin, heterogeneous enhancement, Type II time intensity curve, and diffusion restriction on diffusion weighted images determined by apparent diffusion coefficient. According to breast imaging reporting and data system, mammography suggested malignancy in 50% of cases, US indicated a moderate to high suspicion of malignancy in 77.8% of cases, MRI revealed malignancy in all cases. At a median follow-up time of 48 months (range,8-122 months) for 35 MBC patients, the local recurrence, distant metastasis, and OS rates were 11.4%, 28.6%, and 67.4%, respectively. The benign features of MBC on mammography and US may cause misinterpretation. However, the inclusion of malignant features observed on MRI can improve diagnostic accuracy.

A Study on Prognostic Factors in Management of Breast Carcinoma in A Tertiary Care Hospital

Breast cancer is the most common malignant tumor and leading cause of death in women worldwide. It accounts for 15% of all cancer deaths According to World Health Organisation (WHO), approximately 70% of breast malignancies occur in women with unknown risk factorsThe prognostic factor can be defined as a measurable variable which correlates with natural history of the disease. The most significant factor which influences prognosis in breast cancer is axillary lymph node involvement, which is usually assessed at time of surgery using sentinel lymph node biopsy or axillary lymph node dissection. The number of lymph nodal involvement is also significant. Involvement of 1-3 lymph nodes carry better prognosis than 4-9 and more than 9 lymph nodes involvement. Size of the tumour has long been recognized as a prognostic factor and as predictor of axillary node status, with larger tumours being associated with a bad prognosis and an increased incidence of nodal metastasis. This study is conducted in Department of General Surgery, SVRRGGH, Sri Venkateswara Medical College, Tirupati for a period of more than one and half year after getting approval from Institutional Ethical Committee on March 2021. A prospective study of 50 patients who fulfilled Inclusion Criteria is taken into consideration to know how prognostic factors like tumor size & grade, axillary lymphnode involvement are influencing the prognosis and management of breast carcinoma. Patients who took part in the study were from 28-68 years of age. Majority of people were in the age group of 46-55 years (38%). Increasing age, involvement of axillary lymph nodes, tumors with larger size and higher grade, and lymphovascular invasions are all associated with worse prognosis Keywords: Estrogen Receptor, Progesterone Receptor, Locally Advanced Breast Carcinoma

Molecular-subtype guided automatic invasive breast cancer grading using dynamic contrast-enhanced MRI

Background and objectivesHistological grade and molecular subtype have presented valuable references in assigning personalized or precision medicine as the significant prognostic indicators representing biological behaviors of invasive breast cancer (IBC). To evaluate a two-stage deep learning framework for IBC grading that incorporates with molecular-subtype (MS) information using DCE-MRI. MethodsIn Stage I, an innovative neural network called IOS2-DA is developed, which includes a dense atrous-spatial pyramid pooling block with a pooling layer (DA) and inception-octconved blocks with double kernel squeeze-and-excitations (IOS2). This method focuses on the imaging manifestation of IBC grades and performs preliminary prediction using a novel class F1-score loss function. In Stage II, a MS attention branch is introduced to fine-tune the integrated deep vectors from IOS2-DA via Kullback-Leibler divergence. The MS-guided information is weighted with preliminary results to obtain classification values, which are analyzed by ensemble learning for tumor grade prediction on three MRI post-contrast series. Objective assessment is quantitatively evaluated by receiver operating characteristic curve analysis. DeLong test is applied to measure statistical significance (P < 0.05). ResultsThe molecular-subtype guided IOS2-DA performs significantly better than the single IOS2-DA in terms of accuracy (0.927), precision (0.942), AUC (0.927, 95% CI: [0.908, 0.946]), and F1-score (0.930). The gradient-weighted class activation maps show that the feature representations extracted from IOS2-DA are consistent with tumor areas. ConclusionsIOS2-DA elucidates its potential in non-invasive tumor grade prediction. With respect to the correlation between MS and histological grade, it exhibits remarkable clinical prospects in the application of relevant clinical biomarkers to enhance the diagnostic effectiveness of IBC grading. Therefore, DCE-MRI tends to be a feasible imaging modality for the thorough preoperative assessment of breast biological behavior and carcinoma prognosis.

To study the utility of COX-2 as immunohistochemical prognostic marker in comparison to various histopathological parameters and TNM staging in breast carcinoma: an observational, cross-sectional study protocol

Background: Breast cancer is the most prevalent cancer among women worldwide and is a well-known cause for cancer mortality in females. COX-2 (cyclooxygenase) plays a vital role in development of some human cancers such as lung, colon and breast. It is a potent enzyme that is important for the conversion of arachidonic acid into prostaglandins. These prostaglandins mediate cellular proliferation, apoptosis and angiogenesis which contributes to carcinogenesis. Overexpression of COX-2 has been detected in several malignancies including breast cancer. COX-2 overexpression is regarded as a poor prognostic marker of breast cancer. The present study will aim to study the immunohistochemical expression of COX-2 in breast cancer and compare it with known histopathological parameters thus assessing its prognostic value. Methods: This will be an observational study conducted in the Department of Pathology, JNMC, Wardha (Sawangi). Radical mastectomy specimens will be studied for COX-2 expression by immunohistochemistry in patients diagnosed with breast carcinoma. COX-2 expression will be quantified as immunohistochemical score and results will be correlated with various histopathological parameters. Results: The expected result of our study will suggest an association of COX-2 expression to the factors associated with poor prognosis in breast carcinoma. A positive correlation is expected between larger tumor size, positive lymph node status, higher T stage and N stage and lymphovascular invasion. Conclusions: Conclusions will be drawn from the obtained results of the immunohistochemical study by using COX-2- for detection of overexpression of COX-2 when evaluated with TNM staging, histological grading and molecular types of breast cancer.

Net survival of women diagnosed with breast tumours: a population-based study in Switzerland.

Although the incidence of breast carcinoma in situ has been increasing, the prognosis of breast carcinoma in situ patients has not been extensively investigated. Thus, we aimed to compare the characteristics of invasive breast tumours based on whether or not they were preceded by a breast carcinoma in situ and to estimate the 5-year net survival of patients diagnosed with different breast tumours. Data from women diagnosed with breast tumours between 2003 and 2016 were used in our analyses. Net survival analyses were performed using inverse probability of censoring weights (nonparametric Pohar Perme estimator). Under certain assumptions, differences in survival between the cancer population and the general population can be considered to be attributable to the cancer diagnosis (NS). Descriptive observation of tumour characteristics indicated that invasive breast tumours following a breast carcinoma in situ were more frequently detected at an earlier stage and had less missing information in tumour-specific variables, compared to invasive breast tumours not preceded by a breast carcinoma in situ. Breast carcinoma in situ patients had a 5-year net survival of 1.02 (95% CI: 1.01-1.03), whereas patients diagnosed with invasive breast cancer without a recorded breast carcinoma in situ had a 5-year net survival of 0.89 (95% CI: 0.88-0.90). Patients diagnosed first with breast carcinoma in situ and then with invasive breast cancer had a 5-year net survival of 0.92 (95% CI: 0.85-1.01). Invasive breast tumours that were preceded by a breast carcinoma in situ were detected more frequently at an earlier stage, compared to those that were not. The estimated 5-year net survival of patients with breast tumours was good.

Prognostic value of amino acid metabolism-related gene expression in invasive breast carcinoma.

An increasing number of studies indicated that metabolic reprogramming of amino acid metabolism may either promote or inhibit tumor progression. The purpose of this study was to investigate the ability of a gene risk signature associated with amino acid metabolism to predict the prognosis and immune characteristics of invasive breast carcinoma. LASSO Cox regression analysis was performed to construct and validate the prognostic risk signature based on the expression of 9 amino acid metabolism-related genes. The predictive value of the signature, immune characteristics, and chemotherapeutic drugs was also predicted. Finally, 9 significant genes were examined in MDA-MB-231 and MCF-7 cells, and the predicted chemotherapeutic drugs were also verified. The prognosis of the low-risk group was better than that of the high-risk group. The areas under the curve (AUCs) at 1, 2, and 3 years were 0.852, 0.790, and 0.736, respectively. In addition, the GSEA results for KEGG and GO revealed that samples with a high-risk score exhibited a variety of highly malignant manifestations. The high-risk group was characterized by an increased number of M2 macrophages, a high level of tumor purity, low levels of APC co-stimulation, cytolytic activity, HLA, para-inflammation, and type I IFN response. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) confirmed that MDA-MB-231 and MCF-7 cells express 9 amino acid metabolism-related genes differently. In addition, cell experiments were conducted to examine the effect of cephaeline-induced on cell viability, migration ability, and protein expression of the PI3K/AKT signaling pathway and HIF-1α. We established a risk signature based on 9 amino acid metabolism-related genes for invasive breast carcinoma. Further analyses revealed that this risk signature is superior to other clinical indexes in survival prediction and that the subgroups identified by the risk signature exhibit distinct immune characteristics. Cephaeline was determined to be a superior option for patients in high-risk groups.

Implications of inflammatory cell death-related IFNG and co-expressed RNAs (AC006369.1 and CCR7) in breast carcinoma prognosis, and anti-tumor immunity.

Objective: Interferon-γ (IFN-γ) encoded by IFNG gene is a pleiotropic molecule linked with inflammatory cell death mechanisms. This work aimed to determine and characterize IFNG and co-expressed genes, and to define their implications in breast carcinoma (BRCA). Methods: Transcriptome profiles of BRCA were retrospectively acquired from public datasets. Combination of differential expression analysis with WGCNA was conducted for selecting IFNG-co-expressed genes. A prognostic signature was generated through Cox regression approaches. The tumor microenvironment populations were inferred utilizing CIBERSORT. Epigenetic and epitranscriptomic mechanisms were also probed. Results: IFNG was overexpressed in BRCA, and connected with prolonged overall survival and recurrence-free survival. Two IFNG-co-expressed RNAs (AC006369.1, and CCR7) constituted a prognostic model that acted as an independent risk factor. The nomogram composed of the model, TNM, stage, and new event owned the satisfying efficacy in BRCA prognostication. IFNG, AC006369.1, and CCR7 were closely linked with the tumor microenvironment components (e.g., macrophages, CD4/CD8 T cells, NK cells), and immune checkpoints (notably PD1/PD-L1). Somatic mutation frequencies were 6%, and 3% for CCR7, and IFNG, and high amplification potentially resulted in their overexpression in BRCA. Hypomethylated cg05224770 and cg07388018 were connected with IFNG and CCR7 upregulation, respectively. Additionally, transcription factors, RNA-binding proteins, and non-coding RNAs possibly regulated IFNG and co-expressed genes at the transcriptional and post-transcriptional levels. Conclusion: Collectively, our work identifies IFNG and co-expressed genes as prognostic markers for BRCA, and as possible therapeutic targets for improving the efficacy of immunotherapy.

Abstract 2657: Preclinical model to evaluate the safety and efficacy of PODO83: A monoclonal antibody against podocalyxin that targets tumor growth and metastasis

Abstract Podocalyxin (PODXL) is a highly glycosylated transmembrane sialomucin normally found on the apical free surface of mesothelial, vascular endothelial, luminal mammary epithelial cells, kidney podocytes and pluripotent and hematopoietic stem cells. We were the first to show that PODXL is upregulated on human cancers and an independent predictor of poor prognosis in breast and high-grade serous ovarian carcinoma (HGSOC). We also demonstrated that PODXL expression is crucial for primary tumor growth, local invasion, and experimental metastasis to distant organs. Subsequently, these results were extended to a wide range of other tumor types. We next developed a large series of high-affinity monoclonal antibodies (mAb) to human PODXL and evaluated these for therapeutic activity against the PODXL+ metastatic breast cancer cell line, MDA-MB-231, in xenografted NOD-SCID IL2Rγ-/- (NSG) mice. One of these, PODO83, potently attenuated primary tumor growth and formation of distal metastases. The PODO83 reactive epitope maps to the juxtamembrane stalk domain (non-glycosylated region) of the PODXL core protein. As a promising therapeutic it is imperative to perform toxicity studies and determine if PODO83 adversely affects the function of PODXL on normal tissues. Accordingly, we generated a transgenic mouse strain (C57Bl/6 congenic) replacing 4 of the 8 mouse PODXL-encoding exons with the orthologous human exons (including those encoding the PODO83 epitope). These mice were healthy and we confirmed by immunohistochemistry that they exhibit appropriate PODO83 immunoreactivity in all expected tissues (podocytes, endothelia, etc). Strikingly, administration of PODO83 in vivo at high doses (4 treatments of 5 mg/kg over 14 days) resulted in no overt signs of toxicity. To now fully assess the safety and efficacy profile of the PODO83 mAb in this preclinical humanized mouse model we have developed mouse metastatic tumor cell line expressing human PODXL and will evaluate the ability of PODO83 to inhibit tumor growth and metastasis while sparing normal tissues in vivo. The results from this study will help us advance PODO83 mAb as a safe and effective approach to treating the wide variety of cancer subtypes that express PODXL. Citation Format: Julyanne Brassard, Michael R. Hughes, Pamela Dean, Diana Canals Hernaez, Janella Schwab, Yasmine Lau, Calvin D. Roskelley, Kelly M. McNagny. Preclinical model to evaluate the safety and efficacy of PODO83: A monoclonal antibody against podocalyxin that targets tumor growth and metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2657.

Clinical characteristics and survival of second primary breast carcinoma with extramammary malignancies.

To investigate the characteristics, diagnosis, survival and prognosis of second primary breast carcinoma (SPBC). Records of 123 patients with SPBC in Tianjin Medical University Cancer Institute & Hospital between December 2002 and December 2020 were retrospectively reviewed. Clinical characteristics, imaging features and survival were analyzed and comparisons between SPBC and breast metastases (BM) were made. Of 67156 newly diagnosed breast cancer patients, 123 patients (0.18%) suffered previous extramammary primary malignancies. Of the 123 patients with SPBC, approximately 98.37%(121/123)were female. The median age was 55 years old (27-87). The average diameter of breast mass was 2.7 cm (0.5-10.7). Approximately 77.24% (95/123) of the patients presented with symptoms. The most common types of extramammary primary malignancies were thyroid, gynecological cancers, lung, and colorectal. Patients with the first primary malignant tumor of lung cancer were more likely to develop synchronous SPBC, and those with the first primary malignant tumor of ovarian cancer were more likely to develop metachronous SPBC. When comparing with BM, patients with SPBC were more often older (≥45 years old), at earlier stages (I/II), more microcalcification and less multiple breast masses in imaging. More than half (55.88%) of patients in the metachronous group developed primary breast cancer within 5 years after diagnosis of extramammary primary cancer. The median overall survival time was 71 months. Within 90 months, the prognosis of patients with synchronous SPBC was worse than that of patients with metachronous SPBC (p=0.014). Patients with BM had the worst outcome compared with patients with synchronous SPBC and metachronous SPBC (p<0.001).ER/PR-negative status, an interval of less than 6 months between the onset of two tumors, a late stage of first primary malignancy, and an age of diagnosis of first primary malignancy greater than 60 years predicted a worse prognosis for patients with SPBC. The possibility of SPBC should be considered during the follow-up of patients with primary extramammary malignancy, especially within 5 years of the onset of the first tumor. The stage of first primary malignancy and the age at diagnosis of first primary malignancy have an impact on the prognosis of patients with SPBC.

THE PROGNOSTIC INDICATOR OF TUMOR INFILTRATING LYMPHOCYTES IN BREAST CARCINOMA

Introduction: Breast cancer is one of the common malignant tumors in women. The use of biomarkers ensures breast cancer patients receive optimal treatment. Tumor-infiltrating lymphocytes (TILs) are emerging as one of the key prognostic markers of breast cancer. Our study aims to evaluate percentage of TILs in Objectives And Methodology: tumor tissue, grading TILs based on the recommendations by an International TIL Working Group 2014 &amp; compare with ER &amp; PR status and in relation to concentration of TILs we assess prognosis of breast carcinoma for a period of 6 months. Results: Among 30 study subjects, TILs were of intermediate, high &amp; lower grade in 53.3%, 40% and 6.7% cases respectively. TILs expression was statistically significant in both ER and PR, positive &amp; negative groups (p&lt;0.05). TILs were statistically highly significant as a prognostic marker in hormone negative breast cancers (p&lt;0.05). Conclusion: Our study concludes that high TILs are correlated with favourable survival and response to treatment in breast cancer patients with ER, PR negative molecular subtype

A STUDY OF OCT3/4 EXPRESSION IN HER2/NEU POSITIVE BREAST CANCER PATIENTS

Oct3/4 is found in germ cells is crucial to control pluripotency during normal development. There is mounting evidence for an association between Oct3/4 and carcinogenesis. Thus Oct3/4 immunohistochemistry has been found in studies to be a useful diagnostic technique for pluripotent germ-cell cancers, providing fresh insights into the cancer's histological heterogeneity. The aim is to study role of Oct3/4 expression in HER2/neu positive breast cancer patients. Paraffin embedded breast tumour tissues from 50 HER2/neu positive female breast cancer patients were enrolled in the study. Oct3/4 expression was studied by immunohistochemistry method and correlated with clinical and pathological parameters as well as disease status. Oct3/4 positivity was seen in 16% of HER2/neu positive breast cancer patients. No significant correlation of Oct3/4 expression with age, menopausal status, tumour size, histopathology, grade and BR score was observed. A trend of higher incidence of Oct3/4 expression was noted with lymph node positive (30%) than lymph node negative patients (07%). A significant higher incidence of Oct3/4 expression was noted in patients with advanced stage of disease (32%) as compared to patients with early stage of disease (04%) and in patients with relapse (44%) than patients in remission (10%). A significant higher incidence Oct3/4 expression was observed with respect to disease free survival in univariate survival analysis. In multivariate survival analysis, for disease free survival metastasis entered at step 1 and grade entered at step 2. For overall survival, metastasis is entered at step 1 as significant factor. The Oct3/4 gene expression may be implicated in self-renewal and tumorigenesis via activating its downstream target genes. It might serve as an important biomarker for contemplating the carcinogenesis, progression, metastasis, or invasive potential and prognosis of breast carcinoma. A larger prospective follow-up studies are recommended to further explore Oct3/4 significance.

Overexpression of HMGB3 and its prognostic value in breast cancer.

High mobility group protein B3 (HMGB3) is abundantly expressed in a number of malignancies, contributing to tumor cell growth and predicting poor outcomes. More research on the connection between HMGB3 and breast cancer is needed. The prognostic significance of HMGB3 in breast cancer was examined and validated in this study. Using The Cancer Genome Atlas (TCGA) database RNA sequencing and clinical data, we investigated the associations between HMGB3 expression and tumor mutations, prognosis, and immune infiltration in breast cancer. The Gene Expression Profiling Interactive Analysis (GEPIA), Tumor Immune Estimation Resource (TIMER), breast cancer gene-expression miner (bc-GenExMiner), UALCAN, OncoLnc, cBio Cancer Genomics Portal (cBioPortal), and LinkedOmics databases were applied to examine the levels of expression, mutation, coexpression, and immune correlation of HMGB3 in breast cancer. cBioPortal and the Database for Annotation, Visualization, and Integrated Discovery (DAVID) were used for coexpression and enrichment analyses, respectively. Experimental tests and a separate cohort of breast cancer patients in our center were used for validation. To determine independent risk factors affecting breast carcinoma prognosis, multivariate Cox regression analysis was performed. The Kaplan-Meier method was applied to analyze the connection between HMGB3 expression and overall survival time in breast cancer. Pan-cancer investigation using the GEPIA and UALCAN databases revealed a high level of HMGB3 expression in different malignancies, including breast cancer. HMGB3 might be a potential diagnostic biomarker, according to the receiver operating characteristic (ROC) curve (AUC=0.932). And immunohistochemistry confirmed higher HMGB3 protein expression in breast cancer tissues in clinical samples. Experimental tests also showed that breast cancer cells have higher expression of HMGB3, and knockdown of HMGB3 can promote the proliferation of breast cancer cells and increase sensitivity to chemotherapy. Human epidermal growth factor receptor 2 (HER2), Nottingham Prognostic Index (NPI), basal-like status, nodal status (N+), triple-negative status, and Scarff-Bloom-Richardson (SBR) grade all showed positive correlations with HMGB3 expression. Conversely, HMGB3 expression was negatively associated with the expression of estrogen receptor (ER) and progesterone receptor (PR) in breast cancer. Breast cancer patients with high HMGB3 expression had poor overall survival, which was validated by an analysis of a separate cohort of breast cancer patients in our center. Cox regression analysis identified high HMGB3 expression as an independently associated risk factor for breast carcinoma. The amount of immunological infiltration was substantially linked with the high expression of HMGB3. The chromosome centromeric region, ATPase activity, and the cell cycle are critical areas where HMGB3 is involved, according to enrichment analysis. Therefore, we suspected that HMGB3 might be a potential biomarker for detecting and treating breast carcinoma. Breast cancer tissues had higher HMGB3 expression than normal breast tissues. HMGB3 overexpression may serve as an indicator for poor breast cancer outcomes.

Circulatory RNA based non-invasive detection and diagnosis of breast cancer

Breast carcinoma is the most prevalent and lethal form of carcinoma in women, as well as the most prominent source of cancer-related mortality in women. The most widespread form of non-invasive breast carcinoma is ductal carcinoma in situ (DCIS). Early detection of breast carcinoma improves the chances of rehabilitation and survival, lowering mortality rates. Limitations of mammography as a screening test have made it imperative to develop new, non-invasive, and more convenient alternatives for the prognosis of breast carcinoma. Circulatory RNAs (miRNAs) have been included in a novel category of non-coding, endogenous, small RNA fragments that can be considered gene expression regulators, influencing key processes in cancer development. Peculiar expressions and firmness of circulatory RNAs exhibit a promising possibility of their use as biomarkers in the prognosis of mammary tumor.

The presentation, management and outcome of patients with ductal carcinoma in situ (DCIS) with microinvasion (invasion ≤1 mm in size)—results from the UK Sloane Project

BackgroundThe diagnosis, management and prognosis of microinvasive breast carcinoma remain controversial.MethodsWe analysed the outcomes of patients with DCIS with and without microinvasion diagnosed between 2003 and 2012 within the Sloane project.ResultsMicroinvasion was recorded in 521 of 11,285 patients (4.6%), with considerable variation in reported incidence among screening units (0–25%). Microinvasion was associated with high-grade DCIS, larger DCIS size, comedo necrosis and solid, cribriform architecture (all P < 0.001). Microinvasion was more frequent in patients who underwent mastectomy compared with breast-conserving surgery (BCS) (6.9% vs 3.6%, P < 0.001), and in those undergoing axillary nodal surgery (60.4% vs 30.3%, P < 0.001) including the subset undergoing BCS (43.4% vs 8.5%, P < 0.001). Nodal metastasis rate was low and not statistically significant difference from the DCIS only group (P = 0.68). Following median follow-up of 110 months, 3% of patients had recurrent ipsilateral high-grade DCIS, and 4.2% developed invasive carcinoma. The subsequent ipsilateral invasion was of Grade 3 in 71.4% of patients with microinvasion vs 30.4% in DCIS without microinvasion (P = 0.02). Distant metastasis and breast cancer mortality were higher with microinvasion compared with DCIS only (1.2% vs 0.3%, P = 0.01 and 2.1% vs 0.8%; P = 0.005).ConclusionsThe higher breast cancer mortality with microinvasion indicates a more aggressive disease.

116P Expression of Her2/Neu and Ki-67 proliferation index in gall bladder carcinomas: Clinicopathological significance

Gall bladder carcinomas (GBC) are one of the most common and aggressive biliary tract malignancies causing significant mortality in South-East Asia and South America as a result of advanced stage at presentation, early metastases, and poor outcomes with standard chemotherapy. Overexpression of Her2/Neu is associated with poor prognosis in breast and gastric carcinomas, which is also being studied for GBC. Ki 67 proliferation index, a marker of replicative potential, is high in higher-grade and aggressive tumors.