Neu Status Research Articles

AXILLARY LYMPH NODE METASTASIS IN SONOLOGICALLY NODE-NEGATIVE BREAST CARCINOMA

Objectives: This study describes the risk factors for axillary metastasis in patients with sonologically node-negative breast carcinoma and also develops a predictive model to evaluate the risk of axillary metastasis in these patients. Methods: Patients admitted to the Department of General Surgery with carcinoma breast qualifying the inclusion and exclusion criteria were included in the study for a period of 1 year. Study was conducted to determine the risk factors of Carcinoma breast by evaluating some clinical and pathological parameters of carcinoma breast patients. Results: Out of 102 patients, 41 had axillary metastasis, factors found significant with p<0.05 were T stage, grade of tumor, estrogen receptor (ER), progesterone receptor (PR) < human epidermal growth factor receptor 2 (HER 2) neu status, histology, and lymphovascular invasion. Mathematical model was developed by binary logistic regression analysis and the probability of axillary metastasis is obtained. Conclusion: The present study demonstrated that T stage, grade of tumor, ER, PR, HER 2 neu status, histology, and lymphovascular invasion are associated with a high risk of axillary metastasis and the newly generated tool shows a sensitivity of 87.8% and specificity of 93.44% for an optimum cut off of >0.2708.

Racial Differences in Breast Cancer Survival Between Black and White Women According to Tumor Subtype: A Systematic Review and Meta-Analysis.

Despite effective early-detection approaches and innovative treatments, Black women in the United States have higher breast cancer mortality rates compared with White women. The purpose of this systematic review and meta-analysis is to determine the extent of disparities in breast cancer survival between Black and White women according to tumor subtype. A comprehensive database search was performed for full-text, English-language articles published from January 1, 2000, to December 31, 2022. Included studies compared survival between Black and White female patients with breast cancer within subtypes defined by hormone receptor and human epidermal growth factor receptor 2 (HER2)/neu (HER2; now known as ERBB2) status. Random-effects models were used to combine study-specific results and generate pooled relative risks (RRs) and 95% CIs for breast cancer-specific or overall survival (OS). A protocol for this review was registered in PROSPERO (CRD42021268212). Eighteen studies including 228,885 (34,262 Black; 182,466 White) patients with breast cancer were identified. Compared with White women, Black women had a higher risk of breast cancer death for all tumor subtypes. The summary risk of breast cancer death was 50% higher among hormone receptor-positive HER2-negative [HER2-] tumors (RR, 1.50 [95% CI, 1.30 to 1.72]), 34% higher for hormone receptor+/HER2+ (RR, 1.34 [95% CI, 1.10 to 1.64]), 20% higher for hormone receptor-negative (-)/HER2+ (RR, 1.29 [95% CI, 1.00 to 1.43]), and 17% higher among individuals with hormone receptor-/HER2- tumors (hazard ratio, 1.17; 95% CI, 1.10 to 1.25). Black women also had poorer OS than White women for all subtypes. These results suggest there are both subtype-specific and subtype-independent mechanisms that contribute to disparities in breast cancer survival between Black and White women, which require multilevel interventions to address and achieve health equity.

Lymph Node Metastasis and Its Diagnostic Implications Among Women Possessing Ductal Carcinoma of the Breast

Abstract Background: Lymph node metastasis is a significant prognostic marker in breast cancer treatment and it is associated with poor prognosis. Periodic acid Schiff’s reagent positive complex in metastatic lymph nodes is an indicator of poor prognosis. The metastatic lymph node variables were evaluated including periodic acid–Schiff (PAS) stain and its significance in prognosis and their association was analyzed concerning clinical and microscopic parameters. Objective: The objective of this study is to determine the lymph node metastasis variables, including its size, number of lymph nodes involved, and other associated pathologies. The clinical and microscopic parameters, including immunohistochemistry (IHC) of the tumor, were studied, and their association with lymph nodes was analyzed. Materials and Methods: In this study, the patients who were diagnosed with ductal carcinoma breast along with lymph node metastasis from 2008 to 2022 were included. The metastatic lymph node size, number, and other associated pathologies were evaluated and PAS stain where ever possible applied, and the results were compared concerning patient age, menopause status, tumor size, grade, invasion, necrosis, calcification, and prognosis (Nottingham prognostic index). IHC for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 /neu status along with vimentin and p53 was also applied and compared. Results: The results revealed that the maximum number of patients below 50 years of age was 54 (58.6%), and belonging to the premenopausal group was 50 (54.3%). The common tumor size among these patients was 5 cm, and below 5 cm was 64 (69.5%). The frequent histological grade was grade II 67 (72.8%), similarly, the favorable prognosis was moderate 55 (59.7%). The largest size of lymph nodes retrieved was 4 cm, the maximum number of lymph nodes involved was 17/19, and >3 metastatic lymph nodes were in 54.34% of cases. The other pathologies, which were found in lymph nodes included granulomatous lesion 2 (2.17%), microfilaria 2 (2.17%), and calcification 4 (4.34%). Immunohistochemistry (IHC) results in tumors having positive nodes were ER (16.30%), PR (11.95%), HER2/neu (21.73%), vimentin (16.30%), and p53 (6.52%). On PAS staining, loops and arches were frequently appreciated. Conclusion: This study concludes that metastatic lymph node is a potential predictor of poor prognosis. It synchronizes with other poor prognostic markers, such as younger age, larger tumor size, grade, invasion, and IHC markers, such as HER2/neu, vimentin, and p53. Other than that, PAS being a cheap and easily available stain, it must applied in metastatic lymph nodes for the determination of prognosis. These factors may be used for better management of breast cancer patients.

Evaluation of biomarkers of response in patients with breast cancer with BRCA 1/2 pathogenic variants treated with PARP inhibitors.

e15188 Background: Several prospective studies highlight the pivotal role of PARP inhibitors (PARPi) in treating BRCA-associated breast cancers (BC), demonstrating a significant overall response rate (ORR) of up to 60% in advanced BC patients with BRCA 1/2 germline pathogenic variants (PV). Despite their clinical efficacy, the factors predicting PARPi response, the mechanisms of resistance to PARPi, and the clinical strategies to overcome these challenges are still unknown. The aim of this study is to establish tissue microarrays (TMA) from primary breast tumor tissue from BC patients with BRCA1/2 PVs who were treated with PARPi and identify biomarkers of PARPi resistance. Methods: Stage 4 BC patients with BRCA 1/2 PVs who presented to the University of Texas MD Anderson Cancer Center Breast Medical Oncology clinics and were treated with PARPi between 2008-2023 were identified using our database. Available patient tissue samples were obtained from institutional tumor banks. TMA from breast tumor tissue created and evaluated by our collabrating pathologists for expression of biomarkers:Wee-1, MRE, BP1,and c-Myc. Clinical and tumor characteristics analyzed included:Age at diagnosis, treatment details, tumor characteristics including histological type, hormonal receptor status, Her-2/Neu status, grade, Ki-67 and clinical outcome. Descriptive statistics, the Fisher exact test, and the log rank test were used to report patient characteristics and outcomes. Here we report on initial TMA construct and biomarker analysis. Results: So far TMA from 12 patients treated with PARPi were succesfully constructed. Patient characteristics include: Median age of 36.5 years (29-57). Nine (75%) and 3 (25%) patients had BRCA1 and BRCA2 mutations, respectively. All patients had invasive ductal carcinoma and 9 (75%) had triple negative BC. Most patient (75%) had high nuclear grade BC and median Ki-67 was 75 (15-90). In 11 evaluable patients, the ORR was 72.7%. The median OS was 383.6 months (95% CI 62.5-383.6) and median PFS was 31.5 months (95% CI 10.8-NE). No significant difference in biomarker expression was observed between PARPi-responders and non-responders (Table1). Conclusions: This report presents unique data on novel predictive biomarkers of response and evaluates the evidence for potential biomarkers. Further analysis on a larger TMA cohort is ongoing. [Table: see text]

Association Between Vitamin D Deficiency and Tumor Characteristics in Breast Cancer Patients.

Introduction Breast cancer is the most frequent cancer among women worldwide, but there is little literature regarding the effects of vitamin Donbreast cancer patients in the Indian population. Hence, this study was planned to determine the correlation between vitamin D deficiency and tumor characteristics in breast cancer patients. Methods This was a cross-sectional study conducted in a tertiary healthcare facilityin central India among allnewly diagnosed patients with breast carcinoma who had received primary surgery and pathological confirmation. We performed universal sampling and included 50 patients in the study. We excluded patients with insufficient histopathological reports, those unfit for surgery, and those with hepatic or renal failure, metabolic bone disease, malabsorption, orrecent consumption of vitamin D (patients who had received oral vitamin D in the preceding two weeks, or vitamin D injection in the preceding six months). Results Among the 50 patients, 86% were vitamin D deficient, with a mean deficiency of 23.54. Vitamin D deficiency is most common in the age groups 41-50 years and >60 years, with the mean age group of 51.49 years. The left side is more involved than the right in vitamin D-deficient patients. Most patients were moderately and poorly differentiated, suggesting a significant association between vitamin D deficiency and tumor differentiation. Almost half the patients were estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her-2/neu) status negative with vitamin D deficiency. Vitamin D deficiency was highest in Her-2/neu amplified, luminal A, and B patients. The mean lymph node-positive participants was 4.04, and the mean number of lymph nodes extracted was 15.58 in vitamin D-deficient breast cancer patients. Conclusion The prevalence of low vitamin D status was high among breast cancer patients. There is an association between vitamin D deficiency and tumors with poor prognostic features. Low vitamin D levels were considered a risk factor for ER, PR, and Her-2/neu-negative tumors along with positive lymph node status in breast cancer patients. Vitamin D status is a modifiable risk factor for breast cancer.Thus, it is concluded from this study that vitamin D has a potential role in the prevention of breast cancer, it may reduce its aggressiveness, and its deficiency is associated with an increased risk of breast cancer.

Abstract PO5-05-12: Loco-regional Treatment in De Novo Bone Only Metastatic Breast Cancer; Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a

Abstract Introduction: The impact of loco-regional treatment (LRT) on survival in de novo bone-only metastatic breast cancer (BC) is controversial. The aim of this study is to assess the effect of LRT on survival utilizing international, prospectively acquired data in this cohort of patients. Materials and Methods: Patients with de novo metastatic BC with bone-only metastases were divided into two groups: those receiving systemic therapy only (ST) and those undergoing LRT. Patients who received LRT were divided into two groups: those who received ST after LRT (LRT+ST arm) and those who received ST prior to LRT (ST+LRT arm). Solitary or multiple bone metastases were classified, and factors associated with disease progression were analyzed. Results: There were a total of 744 patients with de novo bone-only metastatic BC treated at each of the participating institutions between 2014 and 2022, with 372 (50%) participants in each arm. Median follow-up was 48 months (32-66, 25-75%). Patients in the LRT group were significantly younger than the ST group [50 (42, 60) vs 55 (44, 66), p=0.0001]. There were no significant differences in grade, Her2 neu and triple negative status, receipt of hormonal therapy and intervention to metastatic sites. During follow-up, 58% (n=217) of patients in ST arm and 32% (n=120) of patients in LRT arm died (p< 0.001). Local progression was observed in 20% of the patients in the ST arm whereas it was 9% in the LRT arm (p=0.0001). Systemic progression occurred more in ST arm; 66% (n=244) compared to 41% (n=152) of patients in LRT group (p< 0.001). The Hazard of death was 64% lower in LRT group than in ST group (HR: 0.36, 95% CI: 0.29-0.45), p<0.0001). The burden of metastatic disease was significantly different between groups with the solitary bone metastasis rate higher in LRT group than the ST only group (50% vs 24%, p< 0.001). However, the LRT group had better overall survival for both solitary (HR: 0.38, 95% Cl: 0.26-0.55) and multiple (HR: 0.38, 95% Cl: 0.29-0.51) bone metastases patients. Within the LRT group, survival rates were similar whether the breast surgery was performed before or after ST.Multivariate Cox analysis showed that LRT and ER/PR positivity significantly decrease the hazard of death (p< 0.05). Conclusion: Analysis of this large multi-institutional patient cohort provides further evidence that LRT improves overall survival and lowers loco-regional recurrence in patients with de novo bone-only metastatic BC. In breast cancer patients with bone-only metastases at presentation, the decision for LRT should be made through a multidisciplinary approach with consideration of surgical therapy at the primary tumor. Citation Format: Atilla Soran, Serdar Ozbas, Lutfi Dogan, Didem Can Trabulus, Jamila El-Azrhi, Kazim Senol, Berk Goktepe, Shruti Zaveri, Salyna Meas, Umut Demirci, Hasan Karanlik, Aykut Soyder, Ahmet Dağ, Ahmet Bilici, Mutlu Dogan, Mehmet Ali Nahit Sendur, Hande Koksal, Mehmet Ali Gulcelik, Neslihan Cabıoğlu, Levent Yeniay, N. Zafer Utkan, Nuri Karadurmus, Gul Daglar, Turgay Simsek, Birol Yildiz, Cihan Uras, Mustafa Tukenmez, Cihangir Ozaslan, Niyazi Karaman, Arda Isik, Berkay Demirors, Efe Sezgin, Vahit Ozmen, Anthony Lucci. Loco-regional Treatment in De Novo Bone Only Metastatic Breast Cancer; Prospective, Multi-Institutional Real-World Data, BOMETIN, Protocol MF14-1a [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-05-12.

Comparison of Four Different Scoring Methods for Ki-67 Percentage in Breast Carcinoma: A Cross-sectional Study

Introduction: In breast cancer, the prognostic role of Ki-67 has been comprehensively studied, and its usefulness has been proven. Ki-67 expression has a prognostic and predictive value in both adjuvant therapy response and neoadjuvant settings. However, the inter and the intraobserver variability in manual counting limits the accuracy of scoring Ki-67 and consequently its application in treatment. Aim: To examine four different methods of Ki-67 estimation to find the most reliable, reproducible and time-efficient scoring methods for Ki-67. Materials and Methods: The present cross-sectional study was conducted in the Department of Pathology, Sree Mookambika Institute of Medical Sciences, Nagercoil, Tamil Nadu, India, from May 2023 to August 2023. Ki-67 immunostained slides of 30 trucut biopsies of invasive breast carcinoma were retrieved and analysed by two observers in a blinded manner. The four different methods of analysis of Ki-67 expression carried out were the global method, the hotspot method, the Eye-10 method and the stepwise counting strategy. The parameters included in the present study were the mean age of the study population, the pre/postmenopausal status, the histopathological type of invasive breast carcinoma, Estrogen receptor (ER), Progesterone Receptor (PR), and Human Epidermal growth factor Receptor 2 (HER2)/neu status, as well as, the interobserver agreement and the mean time taken by the four methods to analyse the Ki-67 expression. Data entry was performed using Microsoft Office Excel 2013, and statistical analysis was conducted using Statistical Package for the Social Sciences (SPSS) software version 20.0. Descriptive statistics for qualitative variables and mean and Standard Deviation (SD) for quantitative variables were used for data analysis. Chi-square tests were used for bivariate analysis with a determined statistical significance of 5% (p-value<0.05). Results: The mean age of the study population was 52.9±9.1 years. The highest interobserver concordance was observed among the observers using the weighted global scoring method, with an Interclass Correlation Coefficient (ICC) of 0.967. This method was time consuming, with the first observer taking a mean±SD time of 5.5±0.8 minutes and the second observer taking 4.6±0.9 minutes. The least time was consumed for performing the Eye-10 scoring, with mean±SD time was 1±0.87 minutes. The stepwise counting and hotspot method demonstrated excellent inter-rater agreement, with a kappa of 0.8304 (p-value<0.001) between both observers. Conclusion: Although the Eye-10 method and stepwise counting took the least time, they are limited by a gray/intermediate zone for scoring compared to the global scoring method and the hotspot method. As a result, the global and/or hotspot method after proper training is a robust and reliable method of assessing Ki-67, with the hotspot method being the most reliable, as the global method is limited by the use of an online tool.

Breast Cancer; Clinical Spectrum and Genetic Abnormalities in Women of Reproductive Age-Retrospective Study.

Objective: To examine the clinical spectrum of breast cancer, its symptoms, presentation, histologic types and different types of its genetic aberrations in the women of reproductive age.Methodology: This Retrospective study was conducted at the Heavy Industries Taxila (HIT) Hospital, Taxila Cantt, from March 2022 to December 2022. The Temporal sampling technique was used to collect the data. We looked at the data of patients with breast cancer that were treated at the HIT hospital Taxila. The retrospective data was collected from the files of the patients who visited HIT Hospital, dated back from January 2011 to December 2020. The study included women of reproductive age with breast cancer symptoms, regardless of whether they had a family history of the disease. The women with metastatic breast lesions and breast trauma were excluded from the study. Age, hormone receptor status, axillary lymph node status, histologic grade and subtype, tumor size margin status, menopausal status, human epidermal growth factor receptor-2 (HER2)/neu status, and the entire genetic spectrum were all included in the charts. The clinical spectrum, staging, and genetic spectrum are all described in tables. Results: The disease's genetic makeup was found to be quite diverse, with abnormalities in genes; ATM, BARD1, CDH1, and BRCA2 making up 2 (3%) each, 3 (4%) breast cancer gene 1 (BRCA1) and BRCA2 abnormalities making up 48 (67%) of the cases. Twelve (16%) of the patients had TP53 mutations, while two (2%) of the patients had NF1 and RECQL gene alterations.Conclusions: This study identifies multiple genes that contribute to the development of breast cancer, including BRCA1, BRCA2, TP53, BARD1 and Cadherin 1 (CDH1) genes.

Clinicopathological Profile of Breast Cancer at a Tertiary Cancer Center in Jharkhand, India: A Descriptive Cohort Study.

Introduction Breast cancer is the most common cancer in females worldwide including Indian urban areas. There is no concrete data on breast cancer epidemiology from the state of Jharkhand, India. Materials and methods The present study is a retrospectively conducted descriptive cohort study. A total of 759 patients were selected from the database from 2012 to 2022. The parameters taken for the study were age, sex, stage at the time of presentation, histological type, estrogen receptor (ER) status, progesterone receptor (PR) status, human epidermal growth receptor 2 (HER2) neu status (HER2/neu), site of metastasis for stage 4 diseases, parity, and significant family history. Results The median age for patients was 49 years (range: 19-91 years), with a clustering of 74.83% of cases between 31 and 60 years of age. Most of the patients were in stage III, with 365 (48.08%) cases. Bone was the commonest site of metastasis and was found in 41.25% of total cases. The total number of hormone receptor-positive patients was 384 (56.2%), the number of HER2/neu positive patients was 210 (30.7%), and triple-negative breast cancer was found in 184 cases (26.93%). Conclusion The pattern found in our Jharkhand patients was very much similar to other Indian studies with slightly more clustering of younger cases. The cases in India are almost a decade younger than the Western population and the same was replicated in our study. This is one of the largest studies on breast cancer profile and epidemiology from the eastern part of India. Most of our patients presented late, leading to a higher number of locally advanced (stage III) and metastatic (stage IV) cases. More awareness is required at the population level, including strict implementation of a robust screening program by our government, for improving the overall outcome.

Can Caspase-3 act as a potential prognostic biomarker in breast cancer? - A retrospective pilot study in central India

Background: Caspase-3 is involved in the apoptosis induced by many agents, including antineoplastic drugs in cancers. Loss of caspase-3 expression and activity has been reported in primary human breast cancers. It is suggested that it might promote tumour development by preventing and reducing senescence. It was a retrospective observational pilot study aimed to evaluate the prognostic potential role of caspase-3 in breast cancer patients.Method: It was a retrospective observational pilot study in which fifty breast cancer patients were enrolled. Haematoxylin and eosin-stained slides of the cases were screened to obtain the best paraffin block for IHC, on which immunohistochemical expression of caspase-3 marker was done and studied. It was correlated with the known prognostic markers of breast cancer.Results: Out of 21 cases with moderate caspase-3 staining, 85.7% cases were grade III and 14.2% were grade II. From 16 cases with strong caspase-3 staining, 75% cases were grading III followed by 25% cases of grade II. There was no significant correlation between caspase-3 staining with histological grade, size of tumour, lymph node involvement, ER, PR and Her2/neu status (p=0.68, 0.24, 0.20, 0.68, 0.45 and 0.11 respectively). Correlation of survival was significantly associated with lymph node involvement (p=0.01) while it was insignificant for tumour size and histological grade (p=0.36 and 0.42 respectively).Conclusion: The survival of breast cancer patients was correlated only with lymph node metastasis. It was better with smaller number of lymph node involvement. While, Caspase-3 did not have any direct association with prognostic markers of breast carcinoma like tumour size, grade of tumour, lymph node and ER, PR and HER-2/neu status. It can be probably used as a prognostic biomarker in future if bigger study is able to establish the significance in breast cancer.

Molecular and Immunohistochemical Alterations in Breast Cancer Patients in Upper Egypt.

Breast cancer (BC) plays a major public health in Egyptian woman. In Upper Egypt, there is an increase in incidence of BC compared to other Egyptian areas. Triple-negative BC, estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-neu-negative, is a high-risk BC that lacks the benefit of specific therapy that targets these proteins. Accurate determination of Caveolin-1(Cav-1), Caveolin-2 (Cav-2) and HER-2/neu status have become of major clinical significance in BC by focusing about its role as a tumor marker for response to different therapies. The present study was performed on 73 female BC patients in the South Egypt Cancer Institute. Blood samples were used for Cav-1, Cav-2, and HER-2/neu genes amplification and expression. In addition, immunohistological analysis of mammaglobin, GATA3, ER, PR, and HER-2/neu was done. There was a statistically significant association between Cav-1, 2 and HER-2/neu genes expression and the age of patients (P< 0.001). There are increase in the level of Cav-1, 2 and increase in HER-2/neu mRNA expression in groups treated with chemotherapy and group treated with both chemotherapy and radiotherapy compared to each group baseline level of genes mRNA expression before treatment. On the contrary, the group treated with chemotherapy, radiotherapy and hormonal therapy revealed increase on the level of Cav-1, 2 and HER-2/neu mRNA expression when compared with their baseline for the same patients before treatment. Noninvasive molecular biomarkers such as Cav-1 and Cav-2 have been proposed for use in the diagnosis and prognosis for women with BC.

Possibilities of predicting the HER2 / neu status in a primary tumor in breast cancer patients using &lt;sup&gt;99m&lt;/sup&gt;Tc-DARPinG3

Aim. To determine informative prognostic criteria for assessing the HER2 / neu status in primary breast cancer using 99mTc-DARPinG3.Materials and methods. The study included 10 patients with breast cancer (T1-4N0-2M0) before systemic therapy, who underwent a radionuclide study using 99mTc-DARPinG3 at a dose of 3,000 μg. Five patients were characterized by HER2 / neu overexpression in primary breast cancer, whereas 5 patients were HER2-negative. For all patients, morphological and immunohistochemical studies and fluorescence in situ hybridization (FISH) of the primary tumor nodule were carried out. Single-photon emission computed tomography (SPECT) of the chest was performed for all patients 4 hours after the injection of 99mTc-DARPinG3.Results. The total activity of 99mTc-DARPinG3 was 522.4 ± 341.8 MBq. The comparative analysis showed that higher uptake of the labeled protein in HER2-positive breast cancer was significant (p = 0.0159, Mann – Whitney U test). The analysis of the ratios showed significant differences in the tumor-to-background ratios in patients with HER2-positive breast cancer (p &lt; 0.0159, Mann – Whitney U test). Based on the logistic regression analysis, a mathematical model was developed to predict the status of HER2 / neu in primary breast cancer patients (specificity and sensitivity 100%; p = 0.0004) using 99mTc-DARPinG3 at a dose of 3,000 mcg 4 hours after the injection of the radiopharmaceutical.Conclusion. The results of the study allow to consider the tumor-to-background ratio 4 hours after the injection of 99mTc-DARPinG3 as an additional prognostic parameter for determining the HER2 / neu status in primary breast cancer.

Outcome of Breast Carcinoma between ER, PR with HER-2/Neu Positive Receptor Status

Background: The most frequent kind of cancer among women is breast cancer. Evidence shows that the receptor profile of primary and metastatic breast cancer tissue differs. Archival-paired pathology samples were evaluated to determine the level of hormone receptor discordance. Objective: To evaluate the efficacy of the most frequently used biological indicators in breast cancer for predicting how well a patient would respond to surgical management and their outcome. Materials and Methods: This comparative Study was conducted in the surgery department, Rajshahi Medical College, Bangladesh, with a Matricentred base Study from January 2019 to December 2021. They also included patients (n=100) for whom tissue from either the main or secondary metastatic location was detectable. Cancers were compared and analyzed for their ER, PR, and Her-2/neu status in both the primary and the metastatic. Results: The discordance rate for ER was 17.7% (2-sided p=0.0039), with 9.7% of tumors changing from ER-positive to ER-negative and 8.0% changing from ER-negative to ER-positive. The discordance rate for PR was 37.3% (2-sided p&lt;0.0001), with Each and every one of these tumors going through a transition from PR-positive to PR-negative. As far as Her-2/neu is concerned, no major discrepancies were discovered. Conclusions: Hormone receptor status is significantly different between primary and metastatic breast cancer samples, as suggested by this dataset. Common instances of PR decline were observed. More than half of the patients had a positive hormone status, and it was found that the illness had spread to other organs in most of these cases.

Correlation of P53 Expression with Clinicopathological Parameters, Hormone Receptors and HER 2 Neu Status in Breast Carcinoma

Background: Progesterone receptor (PR), estrogen receptor (ER) expression, human epidermal growth factor 2 (HER 2 neu) amplification/ overexpression, and p53 nuclear protein accumulation are all significant prognostic biomarkers in breast cancer (BC). This work aims to assess the co-presence of p53 overexpression with ER, PR, and HER 2 neu expression in invasive BC specimens by IHC and compare their expression with various clinicopathological features. Objectives: To evaluate the expression of ER, PR, HER-2neu and p53 in invasive breast carcinoma specimens and to correlate the expression of p53 with ER, PR, HER-2 neu and the clinicopathological parameters. Methods: Cases of Modified Radical Mastectomy received from June 2015 to May 2017 were studied. In addition to hematoxylin and eosin sections, immunohistochemical staining was done for ER, PR, HER 2 neu and p53. The expression of ER, PR, HER 2 neu and p53 was noted and the findings were correlated with other clinicopathological parameters. Results: Among 86 cases studied most of them belonged to the age group 41-60 years (54, 62.8%). A significant positive correlation of p53 over expression with ER and PR positive tumours and Triple Negative tumours was noted. Also p53 overexpression showed a positive significant correlation with tumour grade. Conclusion: P53 overexpression in breast carcinoma indicates an aggressive clinical course and can be used as a marker of poor prognosis.

Dosimetric evaluation of cardiac and left anterior descending artery dose in patients with left-sided breast cancer treated by different techniques of hypofractionated adjuvant radiotherapy after breast conservative surgery

The aims: to dosimetrically evaluate the dose to the heart and left anterior descending artery in left-sided early breast cases using different techniques.&#x0D; Materials and methods: Prospective observational/analytical study done in cases of left-sided BCS referred for adjuvant RT in 54 patients. Patients who underwent left-sided BCS (breast conservative surgery), patients aged between 18- and 75 years performance status ECOG 0-2, histological confirmed DCIS, Invasive Breast Cancer-Stage 1, 2, 3, patients without any evidence of metastatic disease Irrespective of hormonal receptor and HER-2 neu status are included in the study.&#x0D; Results: All the 3 parameters for LAD showed the highest doses with 3DCRT and lowest with VMAT. Thus our study favoured VMAT (p&lt;0.01) as the planning technique to achieve the least doses of LAD. However, for the heart, there was no statistically significant difference between 3DCRT and IMRT (p=0.349) for the average mean dose (Gy). On the other hand, there was a statistically significant difference between 3DCRT Vs VMAT and IMRT Vs VMAT (95 % CI, p&lt;0.01), again favouring VMAT as the choice of planning technique. The average heart max dose(Gy) and average heart V20(%) showed statistically significant benefits with VMAT (p&lt;0.01). There was a statistically significant benefit (p&lt;0.000) with VMAT for both LV parameters. At the same time, there was a statistically significant benefit in terms of ipsilateral lung dose with VMAT(p&lt;0.000), the dose to the right lung, right breast and favoured 3DCRT (p&lt;0.01). PTV95 % (Gy) by 3DCRT, IMRT, and VMAT in our study is 41.01, 41.96, and 41.76, respectively. Though the difference between the 3 techniques seems meagre, there was a statistically significant difference (p&lt;0.012) favouring IMRT.&#x0D; Conclusion: We conclude that using the VMAT technique in radiotherapy for left-sided breast cancer can significantly reduce radiation doses to the heart and LAD, potentially reducing cardiac risk. For all patients, the cardiac doses are considerably decreased for all dose levels without compromising the dose coverage to PTV, which is an advantage over IMRT and 3DCRT

Role of dynamic and parametric whole-body FDG PET/CT imaging in molecular characterization of primary breast cancer: a single institution experience.

The aim of this pilot study was to assess the role of dynamic whole-body PET and parametric imaging in the biological characterization of primary breast cancer. In total 24 histologically proven primary breast cancer lesions in 21 consecutive patients were retrospectively analyzed. Each patient underwent 18F-fluoro-deoxyglucose whole-body dynamic PET-CT before any treatment. Dynamic PET images were acquired in the list mode for a total duration of 70 min. The reconstructed parametric imaging generated Patlak plot-based 'Slope' and 'Intercept' images, from which parametric indices ki and DV were obtained. The standard uptake value (SUV) metric was also obtained by summing the last few frames of the dynamic study. ki, distribution volume (DV) and SUV were correlated with the histological tumor grade, biomarkers [hormone receptors and human epidermal growth factor receptor 2 (HER-2) neu expression] and molecular subtypes (A, B and C) as well as with tumor size, regional nodal metastases and distant metastases. The mean ki was found to be significantly higher in grade III than II lesions (P = 0.005), HER-2 neu positive status (P = 0.04) and molecular subtype B (P = 0.04) as well as in greater than T1 lesions(P = 0.0003 and P = 0.04, respectively) and node-positive lesions (P = 0.009). Though mean ki was not found to be significant for the hormone receptors status (P = 0.08), it showed the best correlation compared to the other parameters (P = 0.8 for DV and P = 0.1 for SUV). Spearman's correlation test, area under the curve (AUC) and mismatch percentage also revealed ki to predict tumor grade (AUC, 0.95; r = 0.7; P = 0.0001), HER-2 neu status and molecular subtypes (AUC, 0.81; r = 0.49 and P = 0.01) along with the hormone receptors status (AUC, 0.83; r = 0.32; P = 0.1). The mean DV failed to show any association with any of the biological or anatomical staging parameters. Though ki was found to be comparable to that of SUV in almost all the assessed parameters, it appeared to be better for predicting hormone receptors status even though both parameters were not statistically significant. Our initial observation in a small cohort of breast cancer patients suggests that ki is promising in stratifying primary breast cancer lesions according to the tumor grade and biological characteristics.

Discordance of Diagnostic Core Biopsy and Final Histopathology Performed after Surgical Resection of Breast Cancer

Objective: To determine the frequency of discordance of receptor status in our breast cancer patients, find out its causes, and suggest remedial measures.&#x0D; Study Design: Retrospective longitudinal study.&#x0D; Place and Duration of Study: Breast clinic and Radiation Oncology Department of Combined Military Hospital Rawalpindi Pakistan from Jan 2018 to Nov 2021.&#x0D; Methodology: Estrogen Receptor, Progesterone Receptor and Her2 Neu status differences between diagnostic tru-cut biopsy and surgical specimen were compared.&#x0D; Results: Receptor status between initial core biopsy and final histopathology of 63 patients were compared. Discordance rates of 05 (7.90%), 13 (20.60%) and 12 (19%) were noted for Estrogen receptor, progesterone receptor and Her2, respectively. The highest discordance noted was for the progesterone receptor, followed by the HER2 receptor and the Estrogen receptor.&#x0D; Conclusion: The highest discordance noted was for the progesterone receptor, followed by the HER2 receptor and the Estrogen receptor. Further studies are required to know more about the causes of receptor status discordance, its impact on treatment decisions and its impact on disease progression and survival.

Study of estrogen receptor, progesterone receptor, and HER-2/neu status in breast carcinoma

Background: Breast cancer treatment depends mainly on hormone receptors (estrogen and PRs) and human epidermal growth factor receptor-2 (HER2)/neu profile. These receptor analyzes determine the patient’s prognosis, treatment, and outcome. Aims and Objectives: The main objective of this study was to correlate the histologic grade of breast carcinoma with hormone receptors and HER2/neu status. Materials and Methods: This is a retrospective analysis of 342 patients treated from January 2016 to December 2021 at Manipal Teaching Hospital, Pokhara, Nepal to determine hormone receptors and HER2/neu status in breast carcinoma. Modified radical mastectomy, breast-conserving surgery, toilet mastectomy, and excisional biopsies were included for statistical correlation between hormone receptors, HER2/neu, histologic grade, and lymph node status. Results: The mean age of the patients was 48.43±9.4 years (29–71). Of the 342 patients, 334 (97.7%) were female and 8 (2.3%) were male. Left breast carcinoma was 5.3% more common than right breast carcinoma. Among them, 34 (9.9%), 245 (71.6%), and 63 (18.4%) were grade I, II, and III, respectively. Grade II were the most common cancer. The smallest tumor size was 0.5 cm and the largest tumor size was 14 cm. Lymph node involvement was 226 (66.1%). The most common histology was invasive ductal carcinoma with 282 (82.5%), lobular carcinoma with 47 (13.8%), medullary carcinoma with 9 (2.6%), and mucinous carcinoma with 4 (1.2%). Immunohistochemical analysis of all breast cancer patients in the present study revealed ER 175 (51.2.7%), PR 146 (42.7%), and HER2/neu 93 (27.2%). Of all male patients, ER was 100% positive, PR was 75% positive, and HER2/neu was 25% positive. According to grading, ER was seen positive in 23 (13.1%) in grade I, 112 (64%) in grade II, and 40 (22.8.1%) in grade III carcinoma (P&lt;0.05). Similarly, PR was 19 (13.1%) in grade I, 95(65.9%) in grade II, and 30 (20.8%) in grade III carcinomas (P&lt;0.05). Moreover, Her/2-neu was 7 (7.5%) in grade I, 63 (67.3%) in grade II, and 23 (24.7%) in grade III carcinomas (P&lt;0.05). In HER2/neu positive cases, it was observed that the positive expression of estrogen receptor (ER) was high as compared to PR. Conclusion: ERs, PRs, and HER2/neu are the most important factors that determine the best treatment, prognosis, and outcome in breast carcinoma.

MULTIMODALITY TESTING OF HER2/NEU MARKER IN BREAST CANCER: A CORRELATIVE STUDY

Currently HER-2/neu status in breast cancer is categorized by immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH) in clinical practice. The amplification of the HER-2/neu gene has a prognostic significance. Quantitative determination of HER-2/neu gene amplification by qPCR or over-expression by qRT-PCR is not routinely used, whereas qPCR based assays can be an alternative method to evaluate HER-2/neu status. We searched literature and databases including the National Institutes of Health’s (NIH), National Library of Medicine (NLM), The National Center for Biotechnology Information (NCBI), PubMed, and Google Scholar. The current study aimed to identify the correlation between FISH, IHC, and real-time-PCR reaction in measuring HER-2/neu expression in breast cancer.

ROLE OF WT1 AS A PROGNOSTIC MARKER IN BREAST CARCINOMA”

Background: Several studies have been done to explore the clinical presentation and management of breast cancer. However, large unexplored area lies in the histopathological diagnosis of breast cancer, which determines both the choice of therapeutic management and also aids in determining the prognosis. This study was carried out to evaluate the role of WT1 expression in breast cancer. Methods: This retrospective study was carried out among 100 parafn blocks of histologically proven invasive breast cancer specimens. WT1 immunohistochemical staining was done on all the hundred cases, while ER, PR and HER-2/NEU status was studied in 93 cases.WT1 expression was assessed in breast carcinoma and its expression was correlated with known histopathological prognostic factors. Results:The mean age of the participants was 56 years. Invasive carcinoma- No special type (NST) was the most common histological type in 84% cases. The maximum number of cases belonged to T2 category (65 %). ER was positive in 53 cases, PR was positive in 40 cases, while HER2/neu was positive in 30 cases. WT1 expression was positive in 30% of the slides and was identied in the nuclei of tumor cells and the expression varied between the tumors.WT1 expression was found to be higher in patients with tumor size above 5cm (61.9%) and positive lymph nodal status. (p value &lt;0.005). Conclusion: Evaluating WT1 expression with more molecular markers prospectively with a longer duration of follow up and assessing the survival rates will provide a better insight and validate the ndings of this study.