Management Of Breast Carcinoma Research Articles

Comprehensive Review of the Potential Anti-Breast Cancer Properties of Various Medicinal Plants

Breast cancer is the most frequent cancer in women throughout the globe, and its management can be difficult due to its complex etiology. Treatment with chemotherapy, surgical procedures, radiation treatment, and hormone therapy are among the most frequently utilized treatments. However, complications and resistance to multiple drugs can cause challenges. This overview addresses how organic medicinal products obtained from edibles and plants can assist with treatment of Breast cancer. The article scrutinizes the ways by which natural substances may exert beneficial impact in the prevention and management of breast carcinoma as well as offers knowledge regarding the therapeutic plant, including its family, part used, kind of extraction, and molecular mechanisms in breast carcinoma. Following an exhaustive analysis of the various plants, we discovered that Peganum normata, Ammi visnaga, Camellia sinensis, Curcuma longa, and Allium sativam L. had potential anti-breast cancer activities. These data were gathered from PubMed, Scopus, and Google Scholar.

Letrozole induced Necrotizing Cutaneous Vasculitis: A Rare Entity

Cutaneous small vessel vasculitis (CSVV) could be due to varied etiologies of which drug induced CSVV is a prime cause. It commonly presents as purpura but necrotizing lesions can be an uncommon presentation of the disease. Aromatase inhibitors like letrozole are newer drugs used in the management of breast carcinoma. There have been few reports of drug induced vasculitis secondary to letrozole. Herein, we report a case presenting with multiple purpura with ulcers and hemopurulent discharge over bilateral legs after letrozole intake for breast carcinoma. Patient was diagnosed with necrotizing CSVV due to letrozole based on history and clinico-histopathological correlation. To the best of our knowledge, this is the first report of letrozole induced necrotizing CSVV from India.

International Academy of Cytology standardized reporting of breast fine-needle aspiration cytology with cyto-histopathological correlation of breast carcinoma.

The International Academy of Cytology (IAC) has developed a standardized approach for reporting the findings of breast fine-needle aspiration cytology (FNAC). Accordingly, there are five chief categories of breast lesions, C1 (insufficient material), C2 (benign), C3 (atypical), C4 (suspicious), and C5 (malignant). The prognostication and management of breast carcinoma can be performed readily on the basis of this classification system. The aim of this study was to classify various breast lesions into one of the above-named categories and to further grade the C5 lesions specifically using the Robinson system. The latter grades were then correlated with modified Scarff-Bloom-Richardson (SBR) grades. This retrospective study was undertaken in the pathology department of a hospital located in the urban part of the city of Bangalore. All FNAC procedures performed on breast lumps spanning the year 2020 were included in the study. A total of 205 breast lesions was classified according to the IAC guidelines into C1 (6 cases, 2.9%), C2 (151 cases, 73.7%), C3 (13 cases, 6.3%), C4 (5 cases, 2.5%), and C5 (30 cases, 14.6%) groups. The C5 cases were further graded using Robinson's system. The latter showed a significant correlation with the SBR system (concordance=83.3%, Spearman correlation=0.746, Kendall's tau-b=0.736, kappa=0.661, standard error=0.095, p≤.001). A standardized approach for FNAC reporting of breast lesions, as advocated for by the IAC, improves the quality and clarity of the reports and assures diagnostic reproducibility on a global scale. Further, the cytological grading of C5 lesions provides reliable cyto-prognostic scores that can help assess a tumor's aggressiveness and predict its histological grade.

Comparative Study between Matrix Rotation Technique versus Wide Local Excision of Carcinoma of the Breast Located in the Upper / Upper Outer Quadrant

Abstract Background The breast is a cornerstone image of femininity, and the heart of womanhood, as nourisher and comforter. These roles evoke the idea of the importance and the affection of this delicate organ has in the minds of women. Breast, according to national cancer institute, is the chief site of cancer in women in Egypt, representing ∼38.8% of total malignancies among Egyptian women; it is a crucial cause of mortality among women. Aim of the Work The aim of this work is to assess and evaluate wide local excision technique as an oncoplastic procedure for management of breast carcinoma in the upper/upper lateral quadrant with matrix rotation technique regarding cosmetic, surgical outcomes, and patient satisfaction. Patients and Methods This prospective randomized controlled study included 30 patients separated into two groupings cancer breast scheduled for oncology breast surgery divided to two equal group: Group I: wide local excision technique. Group II: matrix rotation technique. Conclusion Wide local excision is a safe oncoplastic technique, causing significantly less post- operative hematoma, mild seroma, minimal blood loss, less areolar deviation and better breast symmetry than matrix rotation technique.

Age-related Differences in Spatially Resolved Transcriptomic Profiles of Patients With Hormone Receptor-positive Breast Carcinoma.

Patients' age may influence the response to chemotherapy and the clinical course of breast carcinoma. This study aimed to compare the spatial transcriptomic profiles between younger (≤50 years) and older (>50 years) patients with hormone receptor (HR)-positive breast carcinoma. Seven cases of breast carcinoma were included. We performed digital spatial profiling and bioinformatic analysis to investigate the spatial transcriptomes of the epithelial and stromal compartments. In the epithelial compartment of three young-age breast carcinoma (YABC) cases, we found 21 up-regulated and 7 down-regulated genes. The top two most up-regulated genes were serpin peptidase inhibitor clade A member 1 and serine protease. The gene ontology enrichment analysis revealed a significant up-regulation of genes defining ribosomal structures and functions in YABCs. The gene set enrichment analysis revealed that gene sets defining early and late responses to estrogen, response to interferon-α, and tumor necrosis factor-α signaling were significantly enriched in YABCs. We described for the first time the age-related differences in spatially resolved transcriptomic profiles and up-regulated transcriptional pathways of HR-positive breast carcinoma. Our observations highlight the critical need for age-specific treatment strategies for breast carcinoma management.

Utility of magnetic resonance imaging (MRI) in the management of breast carcinoma

Utility of magnetic resonance imaging (MRI) in the management of breast carcinoma

Causal association between complement system FHR-5, CTRP9, and breast carcinoma in situ: a Mendelian randomization study.

Breast carcinoma in situ accounts for a significant number of newly diagnosed breast cancer cases. However, the cause of this type of cancer is unclear, which has led to debates regarding treatment strategies. A Mendelian randomization (MR) study was conducted to explore whether complement system or complement C1q/tumor necrosis factor-related proteins (CTRPs) are causally associated with breast carcinoma in situ. This two-sample multivariable MR study used genome-wide association study (GWAS) data for all complement system factors and CTRPs. Summary-level statistics were obtained from the breast carcinoma in situ GWAS database. The study employed the MR-Egger method, inverse variance weighted (IVW) method, and weighted median method. Additionally, sensitivity analyses, including the MR-Egger intercept, funnel plot, and leave-one-out analysis, were conducted to address uncertainties and enhance the reliability of the findings. The study indicated that certain immunomodulatory molecules might increase the risk of breast carcinoma in situ, with consistent results. Specifically, CTRP9 showed a 57.0% increased risk [IVW: odds ratio (OR) 0.570 (0.350, 0.928), p < 0.05], and complement factor H (FH)-related protein 5 (FHR-5) was linked to a 67.2% higher risk [IVW: OR 0.672 (0.477, 0.947), p < 0.05]. However, no associations were found with other molecules, suggesting the relationship between immunomodulatory molecules and cancer may be context-specific. This MR study marks the initial identification of a direct link between FHR-5 and CTRP9 and the susceptibility to breast carcinoma in situ. Delving into the roles of immunomodulatory molecules and immune responses within the tumor microenvironment holds considerable importance for the management of breast carcinoma in situ.

Assessment of Clinicopathological Profile and Receptor Status of Breast Cancer Patients at a Tertiary Care Centre in Uttarakhand, India: A Prospective Cohort Study

Introduction: Breast carcinoma has become a major public health problem among both urban and rural populations in India. The management of breast carcinoma depends on hormone receptor status and the pathological properties of the tissue, which serve as important prognostic markers. Aim: The aim of this study was to analyse the clinicopathological parameters and receptor status in breast cancer patients in the Garhwal Region of Uttarakhand. Materials and Methods: This prospective cohort study involved 51 patients who underwent modified radical mastectomy for breast carcinoma at the Department of General Surgery, Government Doon Medical College, Dehradun, Uttarakhand, India. The study was conducted over a period of two years and seven months, from May 2018 to December 2020. Various parameters such as age, side and quadrant of breast involvement, TNM stage, histological grade, receptor status, molecular subtypes, and axillary lymph node status were evaluated. The data was tabulated using Microsoft Excel 2007. The distribution of various receptors in tumour specimens was compared with clinicopathological variables and expressed as percentages. Results: The mean age of the study participants was 52.54±13.24 years, with a male to female ratio of 2:98. In this study, the majority of females (62.74%) belonged to the age group of 40 to 60 years. Left breast carcinoma showed a slightly higher prevalence (52.94%) than right breast carcinoma (47.05%), and the upper outer quadrant was the most commonly involved (50.98%). Infiltrating ductal carcinoma, not otherwise specified, was the most common histological type observed in all patients. The majority of patients (84.31%) had tumour sizes less than 5 cm. Grade-II tumours were the most frequent grade, observed in 34 cases (66.66%). Among the tumour stages, T2 stage accounted for the highest frequency (67%), followed by T3. The authors found that the highest frequency of tumours belonged to N0 stage (29.41%), followed by N1, N2, and N3, respectively. The corresponding rates of luminal A, luminal B, triple-negative, and Human Epidermal Growth Factor Receptor 2 (HER-2)/neu enriched subtypes were 5 (14.7%), 3 (8.82%), 11 (32.5%), and 3 (8.82%), respectively. The cases negative for Oestrogen Receptor (ER) and Progesterone Receptor (PR) were found to have high-grade disease on histological evaluation. Conclusion: The higher percentage of Grade-II and III tumours observed in this study highlights the need to increase health awareness in this area in order to decrease morbidity and mortality. The study recommends that Immunohistochemistry (IHC) classification serves as an important prognostic factor in breast cancer patients.

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 &amp; 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

New LPA1 receptor modulators: Design, synthesis, in-silico, and anticancer studies of triazole and oxadiazole analogs

Lysophosphatidic acid (LPA) is a bioactive signaling molecule that activates LPA1 receptors, which are over expressed in breast cancer. This signaling cascade promotes cancer cell proliferation, survival, metastasis, and angiogenesis. Small molecules that block LPA1 signaling could benefit breast cancer therapy. Novel 1,2,4-triazoles and 1,3,4-oxadiazoles conjugates of benzimidazole/oxazole/thiazole were designed as LPA1 receptor inhibitors, synthesized, and the in-vitro anticancer activity was examined through breast carcinoma cells (MCF-7) by MTT assay. The compounds that reduced the proliferation of MCF-7 cells were further evaluated for their effects on apoptosis, migration, and angiogenesis at IC50 concentration. Suppression of LPA1 protein and gene expression was analyzed by western blot and qRT-PCR techniques. In addition, ligand interactions towards protein and ligand-receptor stability were predicted by molecular interaction studies and molecular trajectory analysis, respectively. The compounds BI-4 and OX-1 exhibited varying levels of cytotoxicity, with IC50 values of 138 μM and 83.25 μM, respectively. They were able to effectively reduce migration and apoptosis as confirmed by AO/EB staining assay. In addition, these compounds were found to significantly reduce the protein and gene expression of LPA1 and angiogenesis genes (Angiogenin-II and Vegf) in MCF-7 cells. Synthesized ligands also showed interactions with the LPA1 receptor and demonstrated good stability in MD simulation. Overall, BI-4 and OX-1 hold promise as potential lead compounds for further exploration of the role of LPA1 receptors in the management of breast carcinoma.

Overall survival of breast cancer patients in association with ESR1 polymorphism

Breast cancer (BC) is the most common carcinoma in women. Genetic polymorphism in estrogen receptor-α (ESR1) gene is involved in alteration in receptor expression, function and evolving as important determinant of breast cancer susceptibility. The present study aimed to evaluate single nucleotide polymorphism (SNP) in breast carcinoma to find out co-relation with overall survival (OS) of breast carcinoma patients. In present study, overall survival of two hundred breast cancer patients with single nucleotide polymorphism was studied in detail. OS was evaluated by Kaplan-Meier method and then analysed with the log-rank test. The cox regression method was used for analyzing data of survival, hazard ratio estimation and its confidence interval value. The significant association of OS was observed with AG genotype of rs9340799 and rs373404617 (Log-rank χ2 = 18.1658, DF = 2, p = 0.0351; χ2 = 5.7632, DF = 2, p = 0.0560 respectively). The genotypes of ESR1 SNP rs9340799 and rs373404617 were predictive of good outcomes of breast cancer. This study suggests that overall survival studies are helpful in investigating progression or regression of the disease which is required for perfect management of breast carcinoma. Future directions include genetic and proteomic-based approaches for breast carcinoma development and progress.

Vascular Endothelial Growth Factor Expression in Breast Carcinoma and its Association with Expression of Estrogen Receptors, Progesterone Receptors and HER-2/neu and Molecular Subtypes

Background: The management of breast carcinoma depends on several molecular markers and tumor stages. In the last decades, estrogen receptors (ER), progesterone receptors (PR), and HER-2/neu have shown good therapeutic responses. Among other molecular markers, vascular endothelial growth factor (VEGF) is becoming more widely used as a prognostic indicator in patients with breast carcinoma. Anti-VEGF therapy already has been proven as an effective chemotherapeutic agent in some other carcinomas. The study aimed to find out the immunohistochemical expression of Vascular Endothelial Growth Factor (VEGF) in breast carcinoma and its possible correlation with the expression of ER, PR, and HER-2/neu and molecular subtypes to evaluate its prognostic value. Material &amp; Methods: This study was conducted in the Department of Pathology, BIRDEM General Hospital, Dhaka, from March 2018 to January 2020. In this study, 45 diagnosed cases of breast carcinoma were enrolled. Slides of all cases were stained with ER, PR, HER-2/neu, and VEGF antibodies following the avidin-biotin-peroxidase staining method. Results: Among 45 cases, 60% showed positive immunohistochemical expression of VEGF. Most of these cases (71.1%) were ER/PR positive. VEGF did not show a significant association with other molecular markers or molecular subtypes. Conclusion: Although, the potential prognostic value of VEGF has not been confirmed. Based on the findings of the current study, it can be assumed that VEGF plays an important role in the pathogenesis of breast cancer. So, it may serve as a useful biomarker for immuno-targeting therapy in patients with breast cancer.

Understanding Breast Cancer: A Key Emphasis on Molecular Signalling Pathways and Phytotherapy

Globally, 2.3 million women have been diagnosed with breast cancer, making it a significant global public health concern [1]. By 2040, the annual rate of new cases is projected to reach 3 million, an increase of nearly 40 percent from 2020 [2]. Lifelong exposures to a variety of endogenous and exogenous variables, as well as the interaction of genetic elements, contribute to the complexity of breast cancerogenesis [3]. Normal human growth is strictly regulated by the signalling pathways that allow cells to communicate with one another and their surroundings. Breast carcinoma is caused by alterations in signalling networks that regulate cell motility, differentiation, cell proliferation, and cell apoptosis. Surgery, radiotherapy, chemotherapy, hormonal therapy, and targeted therapy are the primary forms of breast cancer treatment [4]. However, phytotherapy have shown promise because they are more effective, safer, and have a lower resistance rate than hormone-targeting and chemotherapeutics [5]. Alternatively, plant-derived natural compounds that have anti-cancer potential by targeting impaired signalling pathways such as Wnt/β-Catenin, NF-κB, PI3K/Akt/mTOR, and epithelial-to-mesenchymal-related pathways. This comprehensive review discusses the actual incidence of breast cancer, its risk factors, diagnostic methods, associated pathogenesis theories, and the universal classification of malignant breast tumours. Finally, we accentuate on the role of phytocompounds to reverse the associated molecular abnormalities, for more effective therapy and a better management of breast carcinomas.

Relationship of Tubule Formation, Indian File Pattern and Apocrine Change With Estrogen and Progesterone Receptors and HER2 Immunostaining.

In breast carcinomas, histomorphological features like low-grade and lobular differentiation are associated with estrogen receptor (ER) and progesterone receptor (PR) expression. Apocrine carcinoma is associated with human epidermal growth factor receptor 2 (HER2) positivity. Studies have not emphasized the association between other histological features like tubule formation, Indian file pattern and apocrine change (which may be found in all grades of tumors or as a part of a mixed pattern of no special type) and immunohistochemistry (IHC). The study was designed to find the association between these morphological factors and ER, PR and HER2 status. The presence or absence of tubule formation, Indian file pattern and apocrine change was correlated with ER, PR and HER2 expression in core biopsies of 102 invasive breast carcinomas. Fisher exact test with median unbiased odds ratio was used. Tubule formation and/or Indian file pattern were significantly associated with ER in all tumors (P-value <0.001), as well as separately for grade II, grade III, HER2-negative and HER2-positive tumors. Comparable results were obtained for their association with PR. Apocrine change was significantly associated with HER2 in all tumors (P-value <0.001), as well as separately for grade III, ER-positive and ER-negative tumors. These histomorphological patterns are modest predictors of IHC status in breast carcinomas, even in tumors of higher grade. Knowledge of these morphological correlates of ER, PR and HER2 in breast cancer may serve as an aid in the quality management of breast carcinoma reporting.

Immunohistochemical Expression of Vascular Endothelial Growth Factor in Different Histomorphological Types of Breast Carcinoma.

Background: Breast carcinoma is a heterogenous disease that represent a major health problem in Bangladeshi population. Several molecular markers have been detected over the past several decades, that are important in clinical aspects of breast carcinoma. Most recently, Vascular Endothelial Growth Factor (VEGF) is emerging as a prognostic marker in patients with several types of carcinoma including breast carcinoma. Many anti-angiogenic therapies targeting VEGF has been proven effective in many carcinomas. Objectives:This study was aimed to determine the expression of VEGF in different histomorphological types of breast carcinoma in an attempt to clarify its potential clinical outcome. Materials and Methods: This study was conducted in the Department of Pathology, Bangladesh Institute of Research and Rehabilitation in Diabetes, Endocrine and Metabolic Disorders (BIRDEM) General Hospital, Dhaka from March 2018 to January 2020. In this study, 45 diagnosed cases of breast carcinoma were enrolled. Histopathological slides of all cases were re-evaluated. Thin sections were taken on coated slides from each paraffin block and immunohistochemical staining was done with VEGF antibody. Results: Among 45 cases, 73.3% cases were invasive ductal carcinoma and 13.3% cases were invasive lobular carcinoma. The immunohistochemical expression of VEGF was positive in 60% cases. In this study, 100% cases of in-situ ductal carcinoma, 83.3% cases of invasive lobular carcinoma and 57.6% cases of invasive ductal carcinoma showed overexpression of VEGF. However VEGF expression did not show significant association with histomorphological types. Conclusion: VEGF expression was found in 60% of breast carcinoma cases. It may serve as a potential therapeutic target for the management of breast carcinoma. KYAMC Journal Vol. 13, No. 01, April 2022: 9-12

Prediction of Molecular Subtypes Using Superb Microvascular Imaging and Shear Wave Elastography in Invasive Breast Carcinomas

To investigate the efficacy of the advanced imaging methods, superb microvascular imaging (SMI) and shear wave elastography (SWE) in predicting molecular subtypes in invasive breast carcinomas. A total of 210 biopsy-proven breast carcinomas in 200 patients who underwent ultrasound (US) imaging with SMI and SWE were included in this study. Quantitative analyses were performed using mean elasticity (Emean) score by SWE and vascular index (VI) by SMI. For qualitative assessment of microvascularity, first, lesions were graded according to Adler's classification in four types. Then, a new morphological model was used to classify the microvascular architecture into six patterns: type one, no signal; type two, penetrant; type three, rim-like; type four, dot-like/linear/regional; type five, wheel-like and type six, irregular signals. The correlation between these variables and molecular subtypes, nuclear grade, the Ki-67 levels and axillary status was investigated. The average VI and Emean values were relatively higher in non-luminal subtypes (VI, p=0.002; Emean, p > 0.05). The two microvascularisation models were significantly able to differentiate the molecular subtypes according to the Kruskal Wallis test (p < 0.05). Rim-like, penetrant and regional patterns were primarily observed in luminal subtypes. The dominant pattern in non-luminal subtypes was wheel-like pattern. VI, Emean, Adler's classification and morphological vascularisation model were not significantly correlated with the nuclear grade, Ki-67 index or axillary status. The proposed microvascular categorization model may be more valuable in predicting molecular subtypes of breast carcinomas compared to VI and Emean and may contribute to the management of breast carcinomas as a non-invasive variable.

'Breast Cancer Resistance Likelihood and Personalized Treatment Through Integrated Multiomics'.

In recent times, enormous progress has been made in improving the diagnosis and therapeutic strategies for breast carcinoma, yet it remains the most prevalent cancer and second highest contributor to cancer-related deaths in women. Breast cancer (BC) affects one in eight females globally. In 2018 alone, 1.4 million cases were identified worldwide in postmenopausal women and 645,000 cases in premenopausal females, and this burden is constantly increasing. This shows that still a lot of efforts are required to discover therapeutic remedies for this disease. One of the major clinical complications associated with the treatment of breast carcinoma is the development of therapeutic resistance. Multidrug resistance (MDR) and consequent relapse on therapy are prevalent issues related to breast carcinoma; it is due to our incomplete understanding of the molecular mechanisms of breast carcinoma disease. Therefore, elucidating the molecular mechanisms involved in drug resistance is critical. For management of breast carcinoma, the treatment decision not only depends on the assessment of prognosis factors but also on the evaluation of pathological and clinical factors. Integrated data assessments of these multiple factors of breast carcinoma through multiomics can provide significant insight and hope for making therapeutic decisions. This omics approach is particularly helpful since it identifies the biomarkers of disease progression and treatment progress by collective characterization and quantification of pools of biological molecules within and among the cancerous cells. The scrupulous understanding of cancer and its treatment at the molecular level led to the concept of a personalized approach, which is one of the most significant advancements in modern oncology. Likewise, there are certain genetic and non-genetic tests available for BC which can help in personalized therapy. Genetically inherited risks can be screened for personal predisposition to BC, and genetic changes or variations (mutations) can also be identified to decide on the best treatment. Ultimately, further understanding of BC at the molecular level (multiomics) will define more precise choices in personalized medicine. In this review, we have summarized therapeutic resistance associated with BC and the techniques used for its management.

Synthesis, Radiolabeling, and Preclinical Evaluation of 68Ga/177Lu-Labeled Leuprolide Peptide Analog for the Detection of Breast Cancer.

Objectives: The expansion of novel and potent tumor receptor binding peptides is a promising approach for the precise targeting of various cancer. Leuprolide is a 9-residue peptide analog of gonadotropin-releasing hormone and is extensively used in the treatment of sex hormone-dependent tumors, including prostate, breast, and ovarian cancer. This preclinical study was undertaken to prepare a new radiolabeled leuprolide peptide for the detection of breast carcinoma. Methods: A 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-coupled 9-amino acid leuprolide peptide was synthesized after typical 9-fluorenylmethyl-oxycarbonyl-based solid-phase peptide synthesis and radiolabeled with both 68Ga and 177Lu radionuclides for theranostic use. The systemic pharmacokinetics was done in healthy balb/c mice. The in vitro tumor cell binding affinity was determined on MCF7, T47D, and MDA-MB-231 breast cancer cell lines. In vivo tumor targeting and micro positron-emission tomography imaging was performed on nude mice with MCF7 breast tumor xenografts. Results: The leuprolide peptide was conveniently synthesized by solid-phase synthesis strategy and its identity and purity were validated by mass spectrometry and high-performance liquid chromatography. The peptide radiolabeled efficiently (˃94%) with both diagnostic (68Ga) and therapeutic (177Lu) radionuclides and displayed nanomolar binding potency to all three tested MCF7, T47D, and MDA-MB-231 cell lines. Fast and favorable pharmacokinetics was observed for 68Ga/177Lu-leuprolide in healthy Balb/c mice. In nude mice, 68Ga-leuprolide peptide exhibited rapid clearance from the blood circulation with low to moderate (up to 5% ID/g) uptake/retention by the major body organs. The accumulation in the estrogen receptor-positive MCF7 tumor was 2.24% ± 0.62% ID/g at 45 min p.i, with good tumor to blood and muscle uptake ratios. The radiolabeled peptide was excreted primarily through the renal pathway. Conclusion: The encouraging results of this initial study demonstrate that additional testing of this leuprolide peptide seems to be indicated because of its convincing potential to be a new agent for the management of breast carcinoma.

Evaluation of the Prognostic Value of Ki-67 in Early Stage Breast Cancer

Background: Breast cancer is a disease which have a variety of important features whose different phenotype only partially summarize the underlying biological complexity. Treatment choices in routine management principally rely on the clinical and pathological characteristics of the disease, although molecular classification currently offers information alongside that provided by clinical and pathological examination. The decision to offer adjuvant chemotherapy to patients is not easy and the knowledge of prognostic factors is mandatory. Ki 67 plays an important role in this context, especially in patients who do not have access to genetic signatures. Aim of the work: This study aims to evaluate the value of Ki67 as a prognostic factor in relation to disease free survival and other clinico-pathological factors in Egyptian females with early stage breast cancer. Patients and Methods: Type of study: This is a retrospective cohort study. Study population: It consisted of 124 patients diagnosed with early stage breast cancer. Study Period: They were diagnosed between January 2011 and December 2015. Study setting: The patients were following up in Ain Shams University Hospital clinical oncology department. Information were manually retrieved from the records of the clinical oncology department at Ain Shams university hospitals. Clinical and pathological tumor characteristics were collected using patient charts and pathology reports. Results: Our study showed a significant relation between Ki67 index and estrogen receptors, progesterone receptors and Her2 neu status. Ki67 was found to be statistically significantly correlated to intrinsic subtypes. Our study was unable to find out the effect of Ki67 on disease free survival. Cox regression analysis revealed a statistical significant influence of estrogen receptors status on disease free survival. It also revealed statistical prognostic effect of progesterone receptors and Her2 status on disease free survival. Covariate analysis of results in our study showed that tumor with T4 stage has a significant prognostic effect on disease free survival. Conclusion: ki67 index may have a prognostic role in management of early stage breast cancer in relation to other prognostic markers like hormone receptor status and HER2neu expression. Moreover, immunohisto-chemistry-based subtyping is extremely important to classify breast carcinoma into molecular subtypes that vary in clinic-pathological features and would lead to different prognosis. Thus, molecular subtyping is essential for breast carcinoma management.

Hormone Receptors and Her-2/neu Overexpression in Breast Carcinomas in Patients of West African Origin Seen at Lagos State University Teaching Hospital, Nigeria

Breast carcinoma is a disease of utmost concern to the individual, family, and society at large. The current trend in the management of breast carcinoma also involves hormonal therapy. Consequently, the hormone expression of the tumor in the individual involved must be known if he or she is to benefit from such therapy. This is a prospective study of estrogen and progesterone receptors as well as Her-2/neu overexpression in all breast carcinomas seen at the Lagos State University Teaching Hospital, Ikeja, Nigeria, between April, 1, 2016, and September, 30, 2018. The total number of cases analyzed during the period under study was 107, comprising 105 women and 2 men with an age range of 26 to 88 years and a mean age of 52 ± 13 years. The tumors fell into histologic grade II (71.0%) and grade III (29.0%). They expressed ER, PR, and Her-2/neu positivity in 42.1%, 33.6%, and 30.8% of the cases, respectively. Triple-negative breast cancer was 35.5%. Male breast cancers presented as invasive ductal carcinoma and exhibit similar staining pattern as the female breast cancer. In conclusion, this study shows that breast carcinomas occurred predominantly in females of younger age and present with tumors, most of which were of high grade and exhibit triple negativity. This observation is relevant to any therapeutic decisions and management of these patients. Improvement in breast carcinoma screening programs so that the disease can be detected early is also advocated.