Invasive Ductal Carcinoma Research Articles

ERα status of invasive ductal breast carcinoma as a result of regulatory interactions between lysine deacetylases KAT6A and KAT6B.

Breast cancer (BC) is the leading cause of death among cancer patients worldwide. In 2020, almost 12% of all cancers were diagnosed with BC. Therefore, it is important to search for new potential markers of cancer progression that could be helpful in cancer diagnostics and successful anti-cancer therapies. In this study, we investigated the potential role of the lysine acetyltransferases KAT6A and KAT6B in the outcome of patients with invasive breast carcinoma. The expression profiles of KAT6A/B in 495 cases of IDC and 38 cases of mastopathy (FBD) were examined by immunohistochemistry. KAT6A/B expression was also determined in the breast cancer cell lines MCF-7, BT-474, SK-BR-3, T47D, MDA-MB-231, and MDA-MB-231/BO2, as well as in the human epithelial mammary gland cell line hTERT-HME1 - ME16C, both at the mRNA and protein level. Statistical analysis of the results showed that the nuclear expression of KAT6A/B correlates with the estrogen receptor status: KAT6ANUC vs. ER r = 0.2373 and KAT6BNUC vs. ER r = 0.1496. Statistical analysis clearly showed that KAT6A cytoplasmic and nuclear expression levels were significantly higher in IDC samples than in FBD samples (IRS 5.297 ± 2.884 vs. 2.004 ± 1.072, p < 0.0001; IRS 5.133 ± 4.221 vs. 0.1665 ± 0.4024, p < 0.0001, respectively). Moreover, we noticed strong correlations between ER and PR status and the nuclear expression of KAT6A and KAT6B (nucKAT6A vs. ER, p = 0.0048; nucKAT6A vs. PR p = 0.0416; nucKAT6B vs. ER p = 0.0306; nucKAT6B vs. PR p = 0.0213). Significantly higher KAT6A and KAT6B expression was found in the ER-positive cell lines T-47D and BT-474, whereas significantly lower expression was observed in the triple-negative cell lines MDA-MB-231 and MDA-MB-231/BO2. The outcomes of small interfering RNA (siRNA)-mediated suppression of KAT6A/B genes revealed that within estrogen receptor (ER) positive and negative cell lines, MCF-7 and MDA-MB-231, attenuation of KAT6A led to concurrent attenuation of KAT6A, whereas suppression of KAT6B resulted in simultaneous attenuation of KAT6A. Furthermore, inhibition of KAT6A/B genes resulted in a reduction in estrogen receptor (ER) mRNA and protein expression levels in MCF-7 and MDA-MMB-231 cell lines. Based on our findings, the lysine acetyltransferases KAT6A and KAT6B may be involved in the progression of invasive ductal breast cancer. Further research on other types of cancer may show that KAT6A and KAT6B could serve as diagnostic and prognostic markers for these types of malignancies.

Image Features and Diagnostic Value of Contrast-Enhanced Ultrasound for Ductal Carcinoma In Situ of the Breast: Preliminary Findings.

To explore the image features and the diagnostic value of contrast-enhanced ultrasound (CEUS) for ductal carcinoma in situ (DCIS) of the breast. A total of 96 female patients with a solitary and histologically proven DCIS were analyzed retrospectively, and 100 female cases of invasive ductal carcinoma (IDC) lesions were used as the control group. The Breast Imaging Reporting and Data System (BI-RADS) category of breast lesions was assessed according to conventional ultrasound features. The DCIS lesions were classified into mass type and non-mass type. The CEUS characteristics of these breast lesions were retrospectively analyzed qualitatively and quantitatively. The final gold standard was biopsy or surgery with histo-pathological examination. Comparing the ultrasound images of DCIS with that of IDC, there were significant differences in echo pattern, calcification morphology, and calcification distribution (p < .05 for all). There was a significant difference between DCIS and IDC in enhancement intensity, perfusion defects, peripheral high enhancement, intratumoral vessels, and arrival time (AT) (p < .05 for all). In the logistic multivariate regression analysis, two indicators linked with DCIS were recognized: perfusion defects (p = .002) and peripheral high enhancement (p < .001). In forecasting DCIS, the logistic regression equation resulted in an AUC of 0.689, a specificity of 0.720, and a sensitivity of 0.563. CEUS showed differences in enhancement characteristics between DCIS and IDC, with perfusion defects and peripheral high enhancement being associated with DCIS.

Differentiating HER2-low and HER2-zero tumors with 21-gene multigene assay in 2,295h + HER2- breast cancer: a retrospective analysis.

HER2-positivity is an essential marker for therapeutic decisions, while HER2 expression is heterogenous. In recent years, there has been increasing recognition of a subgroup of breast cancer patients who have low levels of HER2 expression, also known as HER2-low because trastuzumab deruxtecan offers clinical benefit for patients with HER2-low metastatic breast cancer. Despite the growing interest in HER2-low breast cancer, there is limited research on how multigene assays can help differentiate between HER2-low and HER2-negative breast cancer. Among HR + HER2- breast cancer, we compared genomic characteristics between HER2-low and HER2-zero using the 21-gene assay. A retrospective review of clinical records was performed in 2,295 patients who underwent Oncotype DX® test in two hospitals between 2013 and 2020. Patients were classified into two groups as the HER2-zero and HER2-low based on HER2 immunohistochemistry. In cases with HER2 2+, no amplification of HER2 gene was confirmed by silver in situ hybridization. High genomic risk was defined as cases with 21-gene recurrence score (RS) > 25. Multivariable binary logistic-regression analysis was performed. Of these, 944 (41.1%) patients were assigned to the HER2-zero group, while 1351 (58.9%) patients were assigned to the HER2-low group. The average Recurrence Score (RS) was found to be 17.802 in the HER2-zero breast cancer group and 18.503 in the HER2-low group, respectively (p-value < 0.005). When comparing the proportion of high RS between the two groups, the HER2-zero group had a high RS rate of 12.4% (117 out of 944), while the HER2-low group had a high RS rate of 17.0% (230 out of 1351) (p = 0.002). The HER2 score identified by qRT-PCR was 8.912 in the HER2-zero group and 9.337 in the HER2-low group (p < 0.005). In multivariable analysis, HER2-low status was found to be an independent factor for high RS, with an odds ratio of 1.517 (1.172-1.964), independent of ER, PR, and Ki67. Within the subgroup of patients with invasive ductal carcinoma, the high RS rates were 19% in the HER2-low group and 14% in the HER2-zero group. However, when considering all patients, there were no significant differences observed in recurrence-free survival and overall survival between the HER2-low and HER2-zero groups. Within HR + HER2- breast cancer, HER2-low tumors are associated with high RS, especially for histologically invasive ductal carcinoma. A prognostic influence of HER2-low expression among HR + HER2- breast cancer remains as an area that requires further study.

Severe Radiation-Induced Brachial Plexopathy: A Case Report on Radiation Toxicity in a Patient With Invasive Ductal Carcinoma

Severe Radiation-Induced Brachial Plexopathy: A Case Report on Radiation Toxicity in a Patient With Invasive Ductal Carcinoma

Racial disparities in presenting stage and surgical management among octogenarians with breast cancer: a national cancer database analysis.

As the US faces a diverse aging population, racial disparities in breast cancer outcomes among elderly patients remain poorly understood. We evaluate the association of race with presenting stage, treatment, and survival of invasive breast cancer among octogenarians. Women (≥ 80years) with invasive breast cancer were identified in 2004-2020 NCDB. To facilitate comparison, only non-Hispanic Black and non-Hispanic White patients were included; patients of Hispanic ethnicity were excluded. Demographics, tumor characteristics, and treatments were assessed by race. Overall survival was compared using the logrank test. Multivariable logistic and Cox proportional hazard regression models were developed to evaluate the independent association of race with outcomes of interest. Of 222,897 patients, 19,059 (8.6%) were Black. Most patients had stage I ER + HER2- invasive ductal carcinoma. Black patients more frequently had greater comorbidities, low income and education, and advanced stage (p < 0.001 each; ref: White). Following adjustment, Black women had increased likelihood of Stage III/IV over time, as well as increased odds of chemotherapy (AOR 1.22, 95% CI 1.15 - 1.29) and non-operative management (AOR 1.82, 95% CI 1.72 - 1.92; ref: White). Although Black patients had lower survival rates compared to White, race was not associated with 5-year mortality following adjustment for stage, receipt of surgery, and adjuvant treatments (p = 0.34). Inferior survival among elderly Black patients appears be driven by advanced stage at presentation. While such disparities are narrowing in the present era, future work must consider upstream interventions to ensure equitable outcomes for all races.

Pembrolizumab Induced Recall Dermatitis Occurring 5 Years After Radiotherapy

Background and Clinical Significance: Radiation recall dermatitis (RRD) following immune checkpoint inhibitor (ICI) therapy has been infrequently reported. Case Presentation: We present a 47-year-old female patient who developed RRD of the breast following three doses of pembrolizumab administered as an adjuvant treatment post-nephrectomy for Stage III renal cell carcinoma (RCC). Notably, the affected breast had previously undergone external beam radiotherapy 247 weeks earlier for Stage IA invasive ductal carcinoma. She had received no prior chemotherapy at any point. RRD manifested as breast induration, erythema, and peau d’orange, and contraction of breast volume was noted following three cycles of pembrolizumab on week 17 (400 mg dose every 6 weeks). The dermatitis responded rapidly to systemic corticosteroids and no treatment interruption was needed. Conclusion: To date, this is the longest reported interval from completion of radiotherapy to RRD. A literature search underscores the variability in presentation and management of ICI-associated RRD.

Bilobed Lateral Artery Perforator-based Flap for partial breast reconstruction – technique description and results from a ten-year cohort

IntroductionWe present a new technique, the bilobed lateral artery perforator-based flap, for breast-conserving surgery of large central tumors or nearby, combining Zymany’s bilobed flap and a Lateral Intercostal Perforator (LICAP) flap, and its 10-year outcomes. Materials and MethodsWe studied 37 patients with malignant breast tumors near or involving the central skin, without ptosis or desire to correct it, who avoided mastectomy with this modified bilobed flap from 2013 to 2022. The same surgeon operated on them in different institutions. This research project was approved by our ethical committee (n. 2.322.212). ResultsThe mean age was 57.17 (± 12.60) years. The mean specimen weight was 74.32 (±25.84)g, and the mean tumor size was 40.35 (±15.81) mm. Fourteen (37.84%) tumors were larger than 5cm and one was multicentric. Thirty-two (86.49%) patients had invasive ductal carcinomas. Nipple areola complex was removed in 19 (51.35%) cases due to clinical involvement, and immediately reconstructed in two cases with contralateral free grafting. Twenty-one (56.76%) patients received neoadjuvant chemotherapy. Three (8.11%) patients had immediate contralateral mastopexy. Radiotherapy was indicated in all cases. There were 3 (8.11%) minor complications, one positive margin, and no surgical revisions. In a mean follow-up of 39.97 (±29.43) months, there were no local recurrences, 2 metastasis, and one death. Satisfaction and aesthetic results were good or excellent in most cases. ConclusionsThe new technique enabled breast conservation, with high rates of free margins, high levels of satisfaction, few complications in women with large central tumors on small breasts with limited ptosis.

BP03 Presentation Time: 4:18 PM: Seventeen-Year Single Institution Experience with Accelerated Partial Breast Irradiation Using Interstitial Multicathether Brachytherapy after Breast-Conserving Surgery for Low-Risk Invasive and In-Situ Carcinoma of the Female Breast

BP03 Presentation Time: 4:18 PM: Seventeen-Year Single Institution Experience with Accelerated Partial Breast Irradiation Using Interstitial Multicathether Brachytherapy after Breast-Conserving Surgery for Low-Risk Invasive and In-Situ Carcinoma of the Female Breast

Pancancer analysis of the interactions between CTNNB1 and infiltrating immune cell populations.

Recently, evidence has indicated that CTNNB1 is important in a variety of malignancies. However, how CTNNB1 interacts with immune cell infiltration remains to be further investigated. In this study, we focused on the correlations between CTNNB1 and tumorigenesis, tumor progression, mutation, phosphorylation, and prognosis via gene expression profiling interaction analysis; TIMER 2.0, cBioPortal, GTEx, CPTAC, and GEPIA2 database analyses; and R software. CTNNB1 mutations are most found in uterine endometrioid carcinoma and hepatocellular carcinoma. However, no CTNNB1 mutations were found to be associated with a poor prognosis. In addition, CTNNB1 DNA methylation levels were higher in normal tissues than in tumor tissues in cancer except for breast invasive carcinoma, which had higher methylation levels in tumor tissues. The phosphorylation level of the S675 and S191 sites of CTNNB1 was greater in the primary tumor tissues in the clear cell renal cell carcinoma, liver hepatocellular carcinoma, lung adenocarcinoma, pancreatic adenocarcinoma, and breast cancer datasets but not in the glioblastoma multiform dataset. As for, with respect to immune infiltration, CD8 + T-cell infiltration was negatively correlated with the expression of CTNNB1 in thymoma and uterine corpus endometrial carcinoma. The CTNNB1 level was found to be positively associated with the infiltration index of the corresponding fibroblasts in the TCGA tumors of colon adenocarcinoma, human papillomavirus-negative head and neck squamous cell carcinoma, mesothelioma, testicular germ cell tumor, and thymoma. We also identified the top CTNNB1-correlated genes in the TCGA projects and analyzed the expression correlation between CTNNB1 and selected target genes, including PPP4R2, RHOA, and SPRED1. Additionally, pathway enrichment suggested that NUMB is involved in the Wnt pathway. This study highlights the predictive role of CTNNB1 across cancers, suggesting that CTNNB1 might serve as a potential biomarker for the diagnosis and prognosis evaluation of various malignant tumors.

Ki-67 evaluation using deep-learning model-assisted digital image analysis in breast cancer.

To test the efficacy of artificial intelligence (AI)-assisted Ki-67 digital image analysis in invasive breast carcinoma (IBC) with quantitative assessment of AI model performance. This study used 494 cases of Ki-67 slide images of IBC core needle biopsies. The methods were divided into two steps: (i) construction of a deep-learning model (DL); and (ii) DL implementation for Ki-67 analysis. First, a DL tissue classifier model (DL-TC) and a DL nuclear detection model (DL-ND) were constructed using HALO AI DenseNet V2 algorithm with 31,924 annotations in 300 Ki-67 digital slide images. Whether the class predicted by DL-TC in the test set was correct compared with the annotation of ground truth at the pixel level was evaluated. Second, DL-TC- and DL-ND-assisted digital image analysis (DL-DIA) was performed in the other 194 luminal-type cases and correlations with manual counting and clinical outcome were investigated to confirm the accuracy and prognostic potential of DL-DIA. The performance of DL-TC was excellent and invasive carcinoma nests were well segmented from other elements (average precision: 0.851; recall: 0.878; F1-score: 0.858). Ki-67 index data and the number of nuclei from DL-DIA were positively correlated with data from manual counting (ρ = 0.961, and 0.928, respectively). High Ki-67 index (cutoff 20%) cases showed significantly worse recurrence-free survival and breast cancer-specific survival (P = 0.024, and 0.032, respectively). The performances of DL-TC and DL-ND were excellent. DL-DIA demonstrated a high degree of concordance with manual counting of Ki-67 and the results of this approach have prognostic potential.

Crotonylation of MCM6 enhances chemotherapeutics sensitivity of breast cancer via inducing DNA replication stress.

Breast cancer is associated with high morbidity and mortality, which are closely influenced by protein post-translational modifications (PTMs). Lysine crotonylation (Kcr) serves as a newly identified PTM type that plays a role in various biological processes; however, its involvement in breast cancer progression remains unclear. Minichromosome maintenance 6 (MCM6) is a critical component of DNA replication and has been previous confirmed to exhibit a significant role in tumorigenesis. Despite this, a comprehensive analysis of MCM6, particularly regarding its modifications in breast cancer is lacking. In this study, we found MCM6 is upregulated in breast invasive carcinoma (BRCA) and is associated with poorer overall survival by regulating the DNA damage repair mechanisms. Furthermore, MCM6-knockdown resulted in decreased cell proliferation and inhibited the DNA replication, leading to DNA replication stress and sustained DNA damage, thereby enhancing the chemotherapeutic sensitivity of breast cancer. Additionally, SIRT7-mediated crotonylation of MCM6 at K599 (MCM6-K599cr) was significantly upregulated in response to DNA replication stress, primarily due to the disassemebly of the MCM2-7 complex and regulated by RNF8-mediated ubiquitination. Concurrently, kaempferol, which acts as a regulator of SIRT7, was found to enhance the Kcr level of MCM6, reducing tumour weight, particular when combined with paclitaxel, highlighting its potential chemotherapeutic target for BRCA therapy.

Incidence and clinicopathological characteristics of breast cancer patients from a single center study

Chronic diseases may be associated with adverse clinical characteristics of breast cancer outcomes. This study determined the descriptive association of some chronic diseases and clinicopathological characteristics of breast cancer patients in women diagnosed in a single center in Jeddah, KSA. Retrospective data of 196 patients diagnosed with breast cancer (from 2015-2021) was analyzed. Demographics, patients’ health conditions, and tumor properties were investigated. Most women diagnosed with breast cancer were 40-69 years of age. Women with a body mass index (BMI) classification of overweight/obese were extremely significantly more than those who were classified as lean. The tumors reported show that a significant number of samples (87.0%) had tumors between T1 and T2. Significantly more tumors (61.0%) were of grade V, and ~81.0% were histopathologically classified as invasive ductal carcinoma. A significant majority of breast cancers in this population were human epidermal growth factor receptor 2 negative (70%), progesterone receptor positive (58%), and non-triple negative (~93%). In these patients, a BMI classification of overweight/obese is possibly associated with breast cancer. Awareness and knowledge about the correlation of breast cancer with obesity may help to reduce or delay its presence.

Role of Image-Guided Biopsy in Nonpalpable Breast Lesions: A Study in the Sub-Himalayan Region of North India

Background Nonpalpable breast lesions pose a challenge in their early diagnosis. Image-guided biopsy is preferred in these cases so that a pathological diagnosis of breast carcinoma is reached timely for a better prognosis as the disease has an increased chance of successful outcome with early identification and treatment. Objective The study aims at evaluating the role of stereotactic core needle biopsy (CNB) and percutaneous ultrasound-guided core needle biopsy (US-CNB) in diagnosing suspicious nonpalpable breast lesions. Methods Our study included 35 patients with nonpalpable breast lesions and having a Breast Imaging Reporting and Data System (BI-RADS) risk assessment category IV or V on mammography or sonography. These 35 lesions were subjected to percutaneous image-guided (stereotactic or US) biopsy for histopathological analysis. Results Out of a total of 35 cases, 17 were pathologically malignant (48.6%), with the most common subtype being invasive ductal carcinoma (82.3%). Twenty-nine cases underwent US-CNB, 16 (55.1%) of which were malignant and 13 (44.8%) were benign on histopathological evaluation (HPE). The remaining six cases, which on mammography showed no mass but suspicious malignant calcification only, were subjected to stereotactic CNB, out of which one (16.6%) was malignant and five (83.3%) were benign on HPE. Hence, the lesions visible on sonography were more likely to be malignant. Conclusion Sonography and mammography play a complimentary role in detecting breast carcinoma. Percutaneous biopsy under image guidance can be used as an accurate diagnostic alternative to open surgical excisional biopsy to avoid diagnostic delay.

Exploiting common patterns in diverse cancer types via multi-task learning

Cancer prognosis requires precision to identify high-risk patients and improve survival outcomes. Conventional methods struggle with the complexity of genetic biomarkers and diverse medical data. Our study uses deep learning to distil high-dimensional medical data into low-dimensional feature vectors exploring shared patterns across cancer types. We developed a multi-task bimodal neural network integrating RNA Sequencing and clinical data from three The Cancer Genome Atlas project datasets: Breast Invasive Carcinoma, Lung Adenocarcinoma, and Colon Adenocarcinoma. Our approach significantly improved prognosis prediction, especially for Colon Adenocarcinoma, with up to 26% increase in concordance index and 41% in the area under the precision-recall curve. External validation with Small Cell Lung Cancer achieved comparable metrics, indicating that supplementing small datasets with data from other cancers can improve performance. This work represents initial strides in using multi-task learning for prognosis prediction across cancer types, potentially revealing shared mechanisms among cancers and contributing to future applications in precision medicine.

Evaluation of the common skin diseases in patients with malignancies and the cutaneous side effects of cancer treatments

Purpose The diversity of skin diseases in patients with malignancies leads to diagnostic difficulties and complicate cancer treatment. Furthermore, the increasing use of chemotherapy drugs and novel treatment regimens raises the risk of the development of various cutaneous side effects and the need for dermatologists during cancer management. We investigated the skin diseases in patients with malignancies and the cutaneous side effects of cancer treatments. Methods Medical records of cancer patients evaluated in the Dermatology clinic between July 2018 and April 2023 were retrospectively reviewed. Results This study included 872 cancer patients, 374 females and 498 males. Acute myeloid leukaemia was the most common malignancy, followed by multiple myeloma and invasive ductal breast carcinoma. Graft versus host disease was observed in 89 (10.2%) patients after stem cell transplantation and radiodermatitis developed in 16 (1.8%) patients. Maculopapular drug eruption and hand foot syndrome were the most common cutaneous side effects of chemotherapy drugs. Capecitabine was the most common etiologic agent in hand foot syndrome. Cellulitis was the most frequent bacterial infection in cancer patients, whereas herpes zoster was the most frequent viral infection. Among the chemotherapy drugs that caused acneiform drug eruption, cetuximab and cytarabine were notable. Facial erythema was associated with cytarabine use in 27.3% of patients. Conclusion Identifying the common skin diseases in cancer patients and cutaneous side effects due to chemotherapy drugs may help to take preventive measures, develop specific and effective treatments, determine the most appropriate cancer treatment options, and increase patients’ compliance with cancer treatment.

CK5/6 Expression in Molecular Subtypes of Invasive Ductal Carcinoma

CK5/6 Expression in Molecular Subtypes of Invasive Ductal Carcinoma

MiRNAs profile as a signature for cardiovascular disease in long-term breast cancer female survivors: a pilot study

Abstract Background/Introduction Cardiovascular diseases (CVD) is a matter of immediate concern among long term breast cancer (BC) survivors. An early identification of those patients who are at higher risk of developing CVD is warranted to tailor prevention strategies and improve their quality of life. Purpose To identify whether a specific miRNA signature exists in breast cancer female survivors who develop CVD in a long term follow up. Methods We performed cross-sectional comparison of miRNA expression between female BC survivors (i.e. individual with a diagnosis of invasive ductal carcinoma who were free from cancer at 10-year follow up and without known CVD before BC diagnosis) with CVD (n=11) and without CVD (n=11) matched for age, BC grade, treatment received and traditional cardiovascular risk factors. CVD was defined as the incidence of established atherosclerotic cardio- or cerebro-vascular diseases (i.e., ischemic heart disease, carotid endarterectomy, stroke, heart failure), atrial fibrillation or venous thromboembolism. Thirteen miRNAs were selected since they were involved in either BC and CVD. On plasma derived samples, miRNAs expression profile analysis was performed by retro-transcription and real-time PCR assays, using miRNA-specific probes. Results The BC female survivors (mean age 73 years, 70% hypertension, 60% histological grade 2 and 3) were treated with surgery. The majority (76%) received hormone therapy after surgery according to the BC receptor expression. In half of the cohort, radiotherapy was performed. Those female BC survivors developing CVD experienced more commonly cerebral or cardiovascular atherosclerotic events (70%). As reported in Figure 1, some miRNAs analyzed (miR-19a; miR-21; miR-24; miR-125b; miR-195) are upregulated in BC survivors who developed CVD. Of note miR-19a, miR-21 (and miR-195) increase is so significantly relevant to consider these miRNAs as candidate biomarkers. Conclusion(s) In this discovery cohort, a specific miRNA profile signature identified female BC survivors experiencing CVD. Validation of such signatures is needed in a larger cohort as well as mechanistic studies to understand what is the pathophysiological link between the miRNAs identified and vascular health. Nevertheless these miRNAs in both cancer and cardiac diseases are mainly associated with promotion of cell proliferation and inhibition of apoptotic processes. The clinical implications of using a specific miRNA profile as a likely early biomarker of adverse cardiovascular events are indeed of great interest to better preserve BC survivors' health.Figure 1

Prognostic Significance of Angiogenesis in invasive ductal carcinoma

Background: Angiogenesis is essential for tumor growth and metastasis. Axillary lymphnode status has been the most important prognostic factor in operable breast carcinoma, but it does not fully account for the varied disease outcome. More accurate prognostic indicators would help in selection of patients at high risk for disease recurrence and death who are candidates for systemic adjuvant therapy. Microvessel density in invasive ductal carcinoma (measures of tumor angiogenesis) is associated with metastasis and thus may be a prognostic indicator. Objective: To correlate intratumoral and peritumoral angiogenic microvessel density with lymphnode metastasis in invasive ductal carcinoma. Material and Methods: It is a cross sectional observational study, carried out at the department of Pathology, BSMMU from January 2016 to December 2017. A total 48 mastectomy samples with axillary nodes from histologically confirmed invasive ductal carcinoma were included in this study. Weidner method was used for calculating micro vessels density. Sections examined to evaluate the density of angiogenic vessels by immuohistological stain with vWF expression in invasive breast cancer. Correlation between angiogenic vessels density with or without lymphnode metastasis was taken. Results: In this study angiogenic vessel count is more in the intratumoral area than peritumoural area. There was a positive significant correlation between lymphnode metastasis with micro vessel density in both peritumoral and intratumoral areas in Weidner method in vWF stain. J Shaheed Suhrawardy Med Coll 2023; 15(1): 59-65

Identification of Potential Predictive Transcript Isoform-Biomarkers for the Early Diagnosis of Breast Cancer Using Bioinformatics Tools

Background: Several studies have demonstrated that the expression status of isoforms is more informative as a biomarker than overall gene expression. This study aimed to determine highly but significantly expressed transcript isoforms and evaluate their prognostic and diagnostic impact in breast invasive carcinoma (BRCA) stage I patients. Methods: The differentially expressed genes and their transcript isoforms in BRCA stage I were determined using the Cancer Differentially Expressed Isoform and gene (Cancer DEIso) platform based on The Cancer Genome Atlas (TCGA) data. The prognostic and diagnostic impact of significantly upregulated top 10 genes and their transcripts were revealed using the Cancer DEIso tool, the Kaplan-Meier (KM) method, and the Receiver Operating Characteristic Curve (ROC) approach, respectively. Isoform-level protein-protein interactions (PPI) were constructed using the Domain Interaction Graph Guided ExploreR (DIGGER) database. ConsensusPathDB was used to perform pathway enrichment analysis based on the constructed interactions. Results: This study revealed that NM_024037, NM_001143782, and NM_021619 transcript isoforms have significant diagnostic ability with AUC values 93.2%, 77.1% and 75.3%, respectively to distinguish stage I BRCA patients from normal. KM-plot analysis showed that these three isoforms have no prognostic significance in stage I patients, but their upregulation was correlated with decreased survival in BRCA patients regardless of stage. Isoform-based pathway enrichment analyses indicated that these three isoforms involved in chromatin organization, senescense, DNA damage and several signalling pathways which promotes cancer when there is misregulation. . Conclusion: NM_024037, NM_001143782, and NM_021619 transcript isoforms are potential biomarkers for detecting early-stage BRCA. Thus, it is essential to find out how these three isoforms contribute to the development of breast carcinogenesis and evolve a new approach for capturing breast tumors at an earlier stage of the clinical landscape.

Treatment and survival differences between patients with invasive lobular carcinoma versus invasive ductal carcinoma of the breast.

Invasive lobular carcinoma (ILC) exhibits differences in molecular and biological characteristics compared to invasive ductal carcinoma (IDC). We aim to compare breast cancer-specific survival (BCSS) between patients with ILC and IDC. We used data from the Surveillance, Epidemiology, and End Results database (1992-2020). Logistic regression analyses were conducted to identify factors associated with treatment modalities. We examined BCSS at different time points using a cox regression model with time-dependent coefficient. 343,397 patients with IDC and 39,859 patients with ILC were included. Patients with ILC had more advanced stage disease (stage II, 35% vs. 34%; stage III, 16% vs.11%), and higher rate of hormone receptor-positive disease (97% vs. 81%). Compared to patients with IDC, patients with ILC had better BCSS in the first five years (Hazard ratio [HR]=0.71, p <0.001), but worse BCSS in later years (HR=1.30, p<0.001 in year 6-10; HR=1.75, p<0.001 in year 11-15; HR=2.17, p<0.001 in year 16-20). Patients with ILC survive better in early years but worse in later years compared to patients with IDC. Future studies are required to identify patients with ILC who are at risk of late recurrence or mortality. The results of this study add to the currently conflicting literature of survival of ILC and demonstrate the importance of evaluating novel therapeutic approaches and extended therapy for patients with ILC.