Invasive Ductal Carcinoma Research Articles

The Association Between Breast Cancer Predisposing Genetic Variants and Multifocal, Multicentric Breast Cancer.

Breast-conserving surgery is often discouraged in BRCA gene carriers with early onset breast cancer. The genetic variant carrier breast cancers are more likely to be multifocal or multicentric (MFMC). This retrospective study includes newly diagnosed patients with breast cancer undergoing genetic testing between 2010 and 2021 within the Johns Hopkins Regional Health System. After excluding patients who received neoadjuvant chemotherapy or stage IV breast cancers, patients were divided into two groups: those who tested positive for a variant recognized by the National Comprehensive Cancer Network as predisposing the patient to breast cancer (ATM, BRCA1, BRCA2, CHEK2, NF1, PALB2, RAD51C, RAD51D, and TP53) and those who tested negative. Pathologic features of the tumors were compared, focusing on evidence for MFMC disease, defined as more than one malignant foci more than 5mm apart. Among the 282 eligible cases, 69 (24%) were positive for a genetic variant. The variant carriers were younger at diagnosis (p < 0.001), more likely to have invasive ductal carcinoma (p = 0.03), more likely to have undergone mastectomy (p = 0.03), and more likely to have a grade 3 cancer (p = 0.003). Variant carriers were not more likely to have MFMC disease (28% vs. 22%, p = 0.4). A positive genetic variant was not a predictor of MFMC within the entire cohort [odds ratio (OR):1.3, 95% confidence interval (CI) 0.6-2.6, p = 0.5). Genetic variant carrier cancers are not more likely to be MCMF than sporadic cancers.

Breast histopathological imaging using ultra-fast fluorescence confocal microscopy to identify cancer lesions at early stage.

Ultrafast fluorescent confocal microscopy is a hypothetical approach for breast cancer detection because of its potential to achieve instantaneous, high-resolution images of cellular-level tissue features. Traditional approaches such as mammography and biopsy are laborious, invasive, and inefficient; confocal microscopy offers many benefits over these approaches. However, confocal microscopy enables the exact differentiation of malignant cells, the expeditious examination of extensive tissue sections, and the optical sectioning of tissue samples into tiny slices. The primary goal should be to prevent cancer altogether, although detecting it early can help achieve that objective. This research presents a novel Breast Histopathology Convolutional Neural Network (BHCNN) for feature extraction and recursive feature elimination method for selecting the most significant features. The proposed approach utilizes full slide images to identify tissue in regions affected by invasive ductal carcinoma. In addition, a transfer learning approach is employed to enhance the performance and accuracy of the models in detecting breast cancer, while also reducing computation time by modifying the final layer of the proposed model. The results showed that the BHCNN model outperformed other models in terms of accuracy, achieving a testing accuracy of 98.42% and a training accuracy of 99.94%. The confusion matrix results show that the IDC positive (+) class achieved 97.44% accuracy and 2.56% inaccurate results, while the IDC negative (-) class achieved 98.73% accuracy and 1.27% inaccurate results. Furthermore, the model achieved less than 0.05 validation loss. RESEARCH HIGHLIGHTS: The objective is to develop an innovative framework using ultra-fast fluorescence confocal microscopy, particularly for the challenging problem of breast cancer diagnosis. This framework will extract essential features from microscopy and employ a gradient recurrent unit for detection. The proposed research offers significant potential in enhancing medical imaging through the provision of a reliable and resilient system for precise diagnosis of breast cancer, thereby propelling the progression of state-of-the-art medical technology. The most suitable feature was determined using BHRFE optimization techniques after retrieving the features by proposed model. Finally, the features chosen are integrated into a proposed methodology, which is then classified using a GRU deep model. The aforementioned research has significant potential to improve medical imaging by providing a complex and reliable system for precise evaluation of breast cancer, hence advancing the development of cutting-edge medical technology.

Immunohistochemical Expression of Cyclin D1 and p16 in Invasive Breast Carcinoma and Its Association with Clinicopathological Parameters.

Invasive breast cancer (IBC) is a significant health concern globally, contributing to substantial morbidity and mortality among women. Dysregulated cellular proliferation, a hallmark of malignancy, involves molecular pathways modulated by proteins such as cyclin D1 and p16. Understanding their roles in IBC pathogenesis and their association with prognostic parameters is crucial for refining treatment strategies. This retrospective study included 50 female IBC patients who underwent modified radical mastectomy. Histopathological evaluation and immunohistochemical staining for cyclin D1 and p16 were conducted. Associations between protein expression and clinicopathological parameters were analyzed using statistical tests. Cyclin D1 was expressed in 76% of cases, significantly associated with lower tumor grade and lower Ki-67 proliferation index. It also correlated with luminal A/B molecular subtypes. p16 expression was observed in 48% of cases, significantly associated with higher tumor grade, higher Ki-67 index, and triple-negative/Her-2 neu-enriched subtypes. Co-expression of cyclin D1 and p16 was noted in 60% of cases. No significant association was found between protein expression and other parameters. Cyclin D1 and p16 exhibit potential as prognostic markers in IBC. Cyclin D1 expression correlates with less aggressive tumor features and luminal subtypes, suggesting a favorable prognosis and potential predictive value for CDK4/6 inhibitor therapy. Conversely, p16 expression associated with aggressive phenotypes, indicating poor prognosis. Further studies are warranted to validate these findings and explore their clinical implications. Integrating these biomarkers into clinical practice may enhance risk stratification and treatment decisions, ultimately improving outcomes for IBC patients.

Expression of Immune Checkpoint Regulator Cytotoxic T Lymphocyte Antigen 4 (CTLA-4) and Programmed Cell Death Protein Ligand 1 (PD-L1) in Invasive Ductal Carcinoma Breast.

Despite significant advancement in the diagnostic and therapeutic aspects of breast carcinoma, the prognosis remains dismal. Recently, with advances in its understanding, various immune system-based management strategies have been developed. CTLA-4 suppresses lymphocyte reactivity, IL-2 secretion, and IL-2 receptor expression and triggers cell cycle arrest. PD-L1 inhibits the proliferation and cytotoxicity of T cells and inhibits release of cytokines. Hence, we planned to evaluate the immunoexpression of CTLA-4 and PD-L1 in invasive ductal carcinoma breast and seek correlation between their immunopositivity and the clinicopathological parameters. This was a retrospective study conducted on archival material of 50 cases of breast carcinoma tissue microarrays. Clinicopathological details were recorded. All cases were evaluated for immunohistochemical expression of CTLA-4 and PD-L1. Cytoplasmic expression of CTLA-4 and membranous expression of PD-L1 were considered positive and staining intensity was recorded as mild, moderate, and intense. Data was recorded and analyzed. Immunopositivity for CTLA-4 was seen in 92% of cases of breast carcinoma. CTLA-4 staining intensity showed significant association with TNM staging of breast carcinomas (p = 0.036). Age group of the breast carcinoma cases showed a statistically significant correlation with PD-L1 immunoexpression (p = 0.002). No significant correlation was found between all other clinicopathological characteristics and CTLA-4 or PD-L1 immunostaining. Our study shows that CTLA-4 is a more important immune checkpoint regulator in breast carcinomas in comparison to PD-L1. Thus, anti-CTLA-4 immunotherapy might prove to be of immense help in the treatment of invasive ductal carcinoma breast showing overexpression of CTLA-4.

Evaluating the Clinico-Pathological Relationship Between Stromal Tumor-Infiltrating Lymphocytes and Androgen Receptor Expression Across Molecular Subtypes of Invasive Breast Carcinoma.

Breast cancer remains a significant cause of mortality globally, necessitating effective treatment strategies. Neoadjuvant chemotherapy (NAC) is widely employed to minimize tumor burden and prevent local spread, with treatment efficacy varying based on molecular subtypes. Despite advancements, resistance to conventional therapies persists, prompting the exploration of alternative approaches, including immune cell therapy. Tumor-infiltrating lymphocytes (TILs) have emerged as immunological biomarkers in breast cancer, exhibiting associations with molecular subtypes and treatment response. This retrospective study assessed the clinico-pathological relationship between stromal TILs and AR expression across molecular subtypes of invasive breast carcinoma in an Indian cohort. Thirty-seven patients receiving NAC followed by modified radical mastectomy were analyzed for TILs and molecular subtyping. Immunohistochemistry was used to determine hormone receptor status and AR expression. A higher AR positivity was observed in hormone receptor-positive/Her2neu-negative and hormone receptor-positive/Her2neu-positive tumors compared to triple-negative breast cancers (TNBCs). Significant associations were observed between AR expression and tumor grade, but not with age or Her2neu status. Although no significant correlation was found between AR and complete response to NAC, a weak negative correlation between AR and TILs was noted. Notably, TNBCs with negative AR and Ki67 index exhibited poorer responses to NAC, emphasizing the need for adjuvant therapy. These findings underscore the complex interplay between AR, TILs, and treatment response in breast cancer, highlighting the potential of personalized therapeutic approaches. Further research is warranted to elucidate the prognostic significance of AR and its implications for tailored treatment strategies in breast cancer management.

MoAGL-SA: a multi-omics adaptive integration method with graph learning and self attention for cancer subtype classification

BackgroundThe integration of multi-omics data through deep learning has greatly improved cancer subtype classification, particularly in feature learning and multi-omics data integration. However, key challenges remain in embedding sample structure information into the feature space and designing flexible integration strategies.ResultsWe propose MoAGL-SA, an adaptive multi-omics integration method based on graph learning and self-attention, to address these challenges. First, patient relationship graphs are generated from each omics dataset using graph learning. Next, three-layer graph convolutional networks are employed to extract omic-specific graph embeddings. Self-attention is then used to focus on the most relevant omics, adaptively assigning weights to different graph embeddings for multi-omics integration. Finally, cancer subtypes are classified using a softmax classifier.ConclusionsExperimental results show that MoAGL-SA outperforms several popular algorithms on datasets for breast invasive carcinoma, kidney renal papillary cell carcinoma, and kidney renal clear cell carcinoma. Additionally, MoAGL-SA successfully identifies key biomarkers for breast invasive carcinoma.

Differentiation between invasive ductal carcinoma and ductal carcinoma in situ by combining intratumoral and peritumoral ultrasound radiomics

BackgroundThis study aimed to develop and validate an ultrasound radiomics model for distinguishing invasive ductal carcinoma (IDC) from ductal carcinoma in situ (DCIS) by combining intratumoral and peritumoral features.MethodsRetrospective analysis was performed on 454 patients from Chengzhong Hospital. The patients were randomly divided in accordance with a ratio of 8:2 into a training group (363 cases) and validation group (91 cases). In addition, 175 patients from Yanghu Hospital were used as the external test group. The peritumoral ranges were set to 2, 4, 6, 8, and 10 mm. Mann–Whitney U-test, recursive feature elimination, and a least absolute shrinkage and selection operator were used to in the dimension reduction of the radiomics features and clinical knowledge, and machine learning logistic regression classifiers were utilized to construct the diagnostic model. The area under the curve (AUC) of the receiver operating characteristics, accuracy, sensitivity, and specificity were used to evaluate the model performance.ResultsBy combining peritumoral features of different ranges, the AUC of the radiomics model was improved in the validation and test groups. In the validation group, the maximum increase in AUC was 9.7% (P = 0.031, AUC = 0.803) when the peritumoral range was 8 mm. Similarly, when the peritumoral range was only 8 mm in the test group, the maximum increase in AUC was 4.9% (P = 0.005, AUC = 0.770). In this study, the best prediction performance was achieved when the peritumoral range was only 8 mm.ConclusionsThe ultrasound-based radiomics model that combined intratumoral and peritumoral features exhibits good ability to distinguish between IDC and DCIS. The selection of peritumoral range size exerts an important effect on the prediction performance of the radiomics model.

Invasive Squamous Cell Carcinoma of the Nipple: Case Report With Literature Review

Abstract: In this unusual case, a 73-year-old woman presented with bloody discharge from her right breast and skin thickening was observed on subsequent imaging. Clinically, the findings raised concern for Paget disease. A skin punch biopsy was performed, revealing a high-grade infiltrating carcinoma with squamous features. Metaplastic carcinoma was a differential diagnosis, given that this patient had a history of invasive ductal carcinoma and radiation treatment in the same breast. A subsequent central lumpectomy confirmed the diagnosis of invasive squamous cell carcinoma of the nipple, occurring in the context of Bowen disease as a precursor lesion. Notably, there was no evidence of ductal carcinoma in situ in the background breast tissue or conventional invasive ductal carcinoma component. Both in situ and invasive forms of squamous cell carcinomas have been rarely reported in the nipple. This case highlights the importance of considering such a rare diagnosis, especially in patients with a history of breast cancer.

Deciphering molecular landscape of breast cancer progression and insights from functional genomics and therapeutic explorations followed by in vitro validation

Breast cancer is caused by aberrant breast cells that proliferate and develop into tumors. Tumors have the potential to spread throughout the body and become lethal if ignored. Metastasis is the process by which invasive tumors move to neighboring lymph nodes or other organs. Metastasis can be lethal and perhaps fatal. The objective of our study was to elucidate the molecular mechanisms underlying the transition of Ductal Carcinoma In Situ (DCIS) to Invasive Ductal Carcinoma (IDC), with a particular focus on hub genes and potential therapeutic agents. Using Weighted Gene Co-expression Network Analysis (WGCNA), we built a comprehensive network combining clinical and phenotypic data from both DCIS and IDC. Modules within this network, correlated with specific phenotypic traits, were identified, and hub genes were identified as critical markers. Receiver Operating Characteristic (ROC) analysis assessed their potential as biomarkers, while survival curve analysis gauged their prognostic value. Furthermore, molecular docking predicted interactions with potential therapeutic agents. Ten hub genes—CDK1, KIF11, NUF2, ASPM, CDCA8, CENPF, DTL, EXO1, KIF2C, and ZWINT—emerged as pivotal fibroblast-specific genes potentially involved in the DCIS to IDC transition. These genes exhibited pronounced positive correlations with key pathways like the cell cycle and DNA repair, Molecular docking revealed Fisetin, an anti-inflammatory compound, effectively binding to both CDK1 and DTL underscoring their role in orchestrating cellular transformation. CDK1 and DTL were selected for molecular docking with CDK1 inhibitors, revealing effective binding of Fisetin, an anti-inflammatory compound, to both. Of the identified hub genes, DTL—an E3 ubiquitin ligase linked to the CRL4 complex—plays a central role in cancer progression, impacting tumor growth, invasion, and metastasis, as well as cell cycle regulation and epithelial-mesenchymal transition (EMT). CDK1, another hub gene, is pivotal in cell cycle progression and associated with various biological processes. In conclusion, our study offers insights into the complex mechanisms driving the transition from DCIS to IDC. It underscores the importance of hub genes and their potential interactions with therapeutic agents, particularly Fisetin. By shedding light on the interplay between CDK1 and DTL expression, our findings contribute to understanding the regulatory landscape of invasive ductal carcinoma and pave the way for future investigations and novel therapeutic avenues.

Association of Level III Axillary Lymph Node Positivity with Clinicopathological Characteristics in Breast Cancer

Management of breast cancer has gradually shifted from era of radical surgery to present days of multi-modality management and conservatism. While complete axillary dissection is common for node-positive cases, less invasive approaches like sentinel node biopsy are often sufficient for clinically node-negative cases. However, these findings may not apply to all populations, particularly in India where advanced disease presentation is common. The objective of this study is to assess Level III Axillary Lymph Node Positivity with clinicopathological characteristics in Breast cancer. This was a hospital based retrospective observational study on breast cancer patients conducted in single institute from 2016 to 2022. A total of 70 patients with operable breast cancers, who underwent primary tumour resection and complete axillary lymph node dissection, including level III were included in the study. Patients with inoperable and metastatic disease were excluded. Final histopathological examination data was collected and analysed. Most patients (92.9%) underwent Modified Radical Mastectomy, with Infiltrating Ductal Carcinoma (IDC) being the most common histology (90%). Factors significantly associated with level III lymph node positivity included tumour size &gt;4.5cm, nuclear grade III, pathological N3 stage and extra nodal extension. The study found no significant correlation with other factors like age, tumour laterality, location, hormone receptor status, HER2 status, or LVSI. These findings may help predict level III lymph node involvement in breast cancer patients. All these predictive factors should be considered during the axillary dissection.

Clinical validation on role of cancer diagnostic probe in detecting the involved cavity margins missed in permanent pathology of tumor side in breast cancer surgery

Cancer diagnostic probe (CDP) as a newly entered tool in real-time breast cavity margin evaluation showed great improvement in smart margin shaving intra-operatively. This system increased the rate of involved margin detection to 30% with respect to frozen section. In this study for the first time we showed the independent role of CDP in finding the involved cavity side margins which were not diagnosed by permananet pathology of their tumor side interface. Among 147 detected margins by CDP, 23 lesions with invasive component and ductal carcinoma in-situ/ductal cancerization weren’t reported as involved margins in permanent pathology of tumor side. Our gold standard was the histology of cavity margin specimen had been scored as involved lesion by CDP. It seems that even when the permanent pathology of surgical margins is used for final declaration, role of CDP is irreplaceable. This distinguished achievement has been obtained intra-operatively in real-time by CDP while involved report in permanent pathology of tumor margins induce re-surgery for the patient.

Sociodemographic Scenario of Female Patients with Breast Cancer: Bangladesh Perspective

Background: Breast cancer is the leading malignancy among women worldwide, and in Bangladesh, it presents a significant public health concern. The sociodemographic factors such as age, marital status, contraceptive use, and reproductive history have a profound impact on breast cancer incidence, diagnosis, and outcomes. This study examines these characteristics among Bangladeshi female breast cancer patients to provide insights into the unique epidemiological trends in this region. Objective: To analyze the sociodemographic characteristics of Bangladeshi female breast cancer patients and compare the findings with other global and regional studies. Methods: A cross-sectional descriptive study was conducted with 50 female breast cancer patients diagnosed with invasive ductal carcinoma. The patients were selected from the National Institute of Cancer Research &amp; Hospital in Dhaka, and their sociodemographic data were collected using semi-structured questionnaires. Data on age, marital status, contraceptive use, and reproductive history were analyzed and compared with findings from other studies. Results: Among the 50 patients, the majority (64%) were aged 31-50 years, while 28% were between 51-70 years. Only 8% of the patients were aged 18-30, and there were no patients in the 71-90 age group. The majority of the patients (96%) were married, while only 4% were single. History of contraceptive use was reported by 68% of the patients. The study revealed a pattern of early menarche, high parity, and extended breastfeeding, aligning with other LMICs' trends but differing from patterns seen in high-income countries. Conclusion: The sociodemographic profile of breast cancer patients in Bangladesh mirrors patterns seen in other low- and middle-income countries, with younger women comprising the majority of cases. Factors such as early marriage, contraceptive use, and reproductive history play a significant role in the risk of developing breast cancer. These findings ...........

Abstract C042: TMEM doorway score as a predictive biomarker for therapy selection in ER+/HER2- breast cancer

Abstract Background: Endocrine therapy is the standard of care for ER+/HER- breast cancer; but some patients need additional adjuvant chemotherapy to counter the risk of metastasis. While chemotherapy can reduce metastasis, some patients still relapse. Tumor cells metastasize through TMEM (Tumor Microenvironment of Metastasis) Doorways, consisting of a Mena-expressing tumor cell, a macrophage, and a vascular endothelial cell, all in direct contact. High TMEM doorway scores correlate with increased dissemination in mice and metastatic outcomes in ER+/HER2- breast cancer patients. Recent studies show that adjuvant chemotherapy may activate growth in disseminated tumor cells (DTCs). Thus, we hypothesized that patients with high TMEM doorway scores who receive endocrine plus chemotherapy will have worse distant recurrence-free survival (DRFS) than those with lower TMEM Doorway scores, or those who receive endocrine therapy alone. Methods: We conducted a retrospective study on 119 patients with stage I-III, ER+/HER2- unilateral invasive ductal breast carcinoma (age≥18) from 2005- 2018. All underwent surgery and received adjuvant endocrine treatment alone or with chemotherapy. We excluded patients who had metastatic disease at diagnosis, received neoadjuvant chemotherapy, or lacked treatment data. Formalin-fixed paraffin-embedded primary tumor tissues were stained for TMEM doorways. A pathologist categorized the TMEM doorway scores as low, intermediate, or high. Kaplan-Meier curves and Cox-proportional hazard models compared DRFS based on treatment type and TMEM doorway scores. Multivariate logistic regression analyzed the association between macrophage density or TMEM Doorway Score and metastatic outcomes, adjusting for tumor size, grade, and node positivity. Results: Of all patients, 72 received endocrine plus chemotherapy and 47 endocrine therapy alone. In the chemotherapy group, 34 (47.2%) developed metastases, while 38 (52.8%) remained disease-free. In the endocrine alone group, 37 (78.7%) remained disease-free and 9 (19.1%) developed metastases. There was no significant difference in TMEM Doorway Scores between groups (p=0.07). In patients who received endocrine plus chemotherapy, a high TMEM Doorway Score was associated with greater odds of metastasis (OR 6.8; 95% CI 1.35–33.76; p=0.02), controlling for tumor size, grade, and node positivity but not when endocrine therapy was used alone (p=0.817). Patients with high TMEM Doorway Scores had worse DRFS in the endocrine plus chemotherapy group (HR 2.61; 95% CI 1.08–6.27; p=0.03), but not in the endocrine therapy alone group (p=0.77) adjusted similarly. Conclusions: This study highlights potential clinical utility of TMEM Doorway Scores as a predictive biomarker for chemotherapy selection in ER+/HER2- breast cancer patients. Larger trials are needed to confirm these findings and with confirmation, physicians considering giving chemotherapy to ER+/HER2- breast cancer patients might consider pre-treatment stratification using TMEM Doorway Scores to mitigate the risk of chemotherapy-induced metastasis. Citation Format: Priyanka Parmar, Andrew Miller, Burcu Karadal-Ferrena, Suryansh Shukla, Cien Huang, Mindy Ginsberg, Chedva Rosenbaum, Malka Felder, Chenxin Zhang, John S. Condeelis, Xiaonan Xue, Thomas E. Rohan, Joseph A. Sparano, Jesus D. Anampa, David Entenberg, Maja H. Oktay. TMEM doorway score as a predictive biomarker for therapy selection in ER+/HER2- breast cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C042.

Comprehensive characterization of invasive mammary carcinoma with lobular features: integrating morphology and E-cadherin immunohistochemistry patterns.

Breast cancer treatment prioritizes molecular subtypes over histologic types. However, considering the unique biological behavior of invasive lobular carcinoma (ILC), its diagnosis is crucial for patient management. Therefore, this study aimed to review breast cancer cases, focusing on the E-cadherin patterns and lobular morphology of cases misclassified in the original reports. A comprehensive review was conducted on 481 breast cancer biopsy cases diagnosed as invasive breast carcinoma of no special type (IBC-NST) or ILC with E-cadherin staining. These cases were categorized into six groups based on tumor morphology (ductal/lobular) and E-cadherin expression pattern (membranous/loss/aberrant): (1) ductal/membranous, (2) lobular/loss, (3) lobular/aberrant, (4) mixed, (5) ductal/loss or aberrant, and (6) lobular/membranous. In 211 cases (43.8%), an E-cadherin pattern indicating ILC (loss and aberrant) was observed alongside lobular morphology, representing 5.52% of all breast cancer biopsies during the relevant period. Moreover, 181 cases (37.6%) showed a membranous pattern with ductal morphology, 4 (0.8%) were mixed IBC-NST and ILC, and 85 (17.7%) exhibited discordance between morphology and E-cadherin expression. Notably, only 25.9% (15/58) of cases in group 3, characterized by aberrant E-cadherin patterns, were initially diagnosed as ILC, highlighting a significant diagnostic discrepancy. In group 6, where membranous E-cadherin pattern was present with lobular morphology, only 3.4% (2/58) were diagnosed as ILC in the original reports, indicating diagnostic challenges in morphology and immunohistochemistry discordance. Similarly, in group 5, which had ductal morphology with loss or aberrant E-cadherin expression, the initial diagnosis rate of IBC-NST was 33.3% (9/27), reflecting the complexities in interpreting discordant cases. In real-world practice, diagnosing ILC often heavily depends on E-cadherin results. This study emphasizes the need for diagnostic clarification in cases with discordance between morphology and E-cadherin patterns.

Effect of different treatment strategies on modified Glasgow Prognostic Score (mGPS) in patients with breast cancer

BackgroundThere are various treatment options for breast cancer, but a delayed diagnosis at an advanced stage negatively affects overall survival. Our objective is to investigate the prognostic significance of the modified Glasgow Prognostic Score (mGPS) with different treatment modalities.Materials and methodsThe study was a longitudinal cohort conducted in the Biochemistry laboratory of the Institute of Basic Medical Sciences at Khyber Medical University. Enrolling 121 patients with invasive breast carcinoma from November 2018 to February 2021, blood samples were collected at various stages. Data analysis utilized SPSS® version 22, employing the Kaplan–Meier method for overall survival (OS) calculation. The log-rank test assessed P-values for OS, and the chi-square test analyzed the association of modified Glasgow Prognostic Score (mGPS) with different treatments. Statistical significance was considered for results with a P-value (p < 0.05).ResultsThe study results indicated that mGPS 2 was linked to lower overall survival, while mGPS 0 and 1 were associated with good overall survival. Chemo-endocrine therapy exhibited the highest median survival of 40.9 months compared to other treatment options. Conversely, chemoradiotherapy combined with targeted therapy demonstrated the lowest overall median survival of 22.5 months.ConclusionThe findings of the current research suggested that mGPS could be used as a prognostic screening tool in patients with breast cancers receiving different therapeutic modalities.

Mutations Matter: Unravelling the Genetic Blueprint of Invasive Lobular Carcinoma for Progression Insights and Treatment Strategies.

Invasive Lobular Carcinoma (ILC) presents a distinct subtype of breast cancer, representing 10-15% of cases, with unique clinical and molecular features. Characterized by a non-cohesive, single-file invasion pattern, ILC is typically estrogen receptor (ER)- and progesterone receptor (PR)-positive but human epidermal growth factor receptor 2 (HER2)-negative. Despite favorable prognostic features, its highly metastatic nature and predilection for atypical sites contribute to lower long-term survival compared to invasive breast carcinoma of no special type (NST). ILC's genetic landscape includes mutations in various genes (CDH1, BRCA2, ATM, etc.) and signaling pathways that impact treatment responses, especially in endocrine treatment. Furthermore, the diverse ILC subtypes complicate its management. Current challenges in chemotherapy, along with the targeted therapies, are also discussed. The present article aims to comprehensively review the recent literature, focusing on the pathological and molecular aspects of ILC, including associated genetic mutations influencing disease progression and drug resistance.

Lower FGFR2 mRNA Expression and Higher Levels of FGFR2 IIIc in HER2-Positive Breast Cancer.

Fibroblast growth factor receptor 2 (FGFR2) has been associated with breast cancer. We performed in silico analyses to investigate the FGFR2 mRNA expression and splice variants associated with breast cancer subtypes. Online databases, including cBioPortal and TCGA SpliceSeq, were used to examine the association between the FGFR2 expression and splice variants with breast cancer subtypes. A higher FGFR2 mRNA was significantly associated with luminal, oestrogen receptor (ER)-positive breast cancers, and invasive lobular carcinomas, whereas a lower FGFR2 was associated with human epidermal growth factor receptor 2 (HER2)-positive breast cancer and invasive ductal carcinomas. The epithelial alternatively spliced FGFR2 IIIb isoform was significantly enriched in ER+ breast cancer, while the mesenchymal FGFR2 IIIc isoform was significantly prevalent in HER2+ cancer. Increased levels of FGFR2 and IIIb splice isoforms are associated with less aggressive breast cancer phenotypes, while decreased levels of FGFR2 and increased IIIc splice isoform are associated with more aggressive phenotypes.

ZNAČAJ DIGITALNE STEREOTAKSIJSKE BIOPSIJE U KORELACIJI SA PATOHISTOLOŠKIM POSTOPERATIVNIM NALAZIMA

Aim : This research was conducted with the aim of analyzing the accuracy and diagnostic value of digital stereotactic breast biopsy compared to the postoperative histopathological findings. Methods : A retrospective-prospective study was carried out over a period of 10 months, involving 30 female patients who underwent stereotactic breast biopsy. Data were collected on BI-RADS status, histopathological findings after stereotactic breast biopsy and after surgical excision, basic demographic and relevant medical history data. The patients were divided according to the degree of malignancy into three groups: patients with benign, patients with suspicious and patients with malignant pathohistological findings. The BIS and RIS systems were used for data collection, and the data were statistically analyzed using STATISTICA for Windows. Results : All patients had a radiological finding of BI-RADS 3 or higher. Histopathological results after stereotactic biopsy showed benign findings in 17 patients (B1 and B2), borderline malignant changes were present in 4 patients (B3), one patient had a lesion suspicious for malignancy (B4), and 8 had confirmed malignant lesions (B5). Out of the total 30 patients, 13 underwent surgical treatment. Postoperative histopathological findings in 4 patients showed benign changes, 6 patients had an invasive form of carcinoma, including 5 with invasive NST breast carcinoma and one characterized as invasive ductal breast carcinoma, while three patients had Ductal Carcinoma In Situ (DCIS). A correlation test was performed between the estimated degree of malignancy from the pathohistological findings after stereotaxic biopsy and after surgical operation. Spearman's ρ test showed a significant correlation between the two methods (p &lt; 0.001). Conclusion : The results of histopathological analysis of samples obtained through the stereotactic biopsy method largely correlate with the postoperative histopathological diagnosis in patients who underwent surgical treatment. Keywords : digital stereotactic breast biopsy, PHD findings, BI-RADS, NST, Ductal Carcinoma In Situ.

Phosphorylated protein kinase R (PKR)-like endoplasmic reticulum kinase (PERK) expression in breast cancer is correlated with malignant proliferation and histological grading.

This study aims to detect the expression of phosphorylated PERK in breast cancer using immunohistochemistry and explore its significance. We examined 134 cases of formalin-fixed and paraffin-embedded breast cancer tissues. It was found that the expression of phosphorylated PERK in ductal carcinoma was higher than that in lobular carcinoma, and the difference between them was statistically significant, suggesting that phosphorylated PERK played different roles in the occurrence and development of different types of breast cancer. Compared with Ki-67-negative breast cancer tissues, phosphorylated PERK has higher expression in Ki-67-positive tissues and is positively correlated with Ki67 expression, indicating that phosphorylated PERK plays an important role in breast cancer's malignant proliferation and progression. We also found a positive correlation between phosphorylated PERK expression and the histological grading of invasive ductal carcinoma, indicating that phosphorylated PERK plays an important role in the differentiation of invasive ductal carcinoma. Our study revealed the differential expression of phosphorylated PERK in subtypes of breast cancer. It contributed to the malignant proliferation of breast cancer and tissue differentiation of invasive ductal carcinoma of the breast.

Angiosarcoma of the Breast: Case Report

Angiosarcoma is a rare and aggressive tumor of the breast arising from endothelial cells. It is usually associated with chronic lymphedema or radiation therapy. The diagnosis is made by biopsy and there is no specific finding on mammography. In this study, we report a 59-year-old woman with a history of radiotherapy for invasive ductal carcinoma who subsequently developed primary angiosarcoma of the breast. Angiosarcoma of the breast was first documented in 1887 and is classified as primary and secondary. While surgical R0 resection is recommended for the treatment of these tumors with unclear etiology, the significance of axillary lymph node dissection remains uncertain. Adjuvant radiotherapy has been shown to reduce the local recurrence rate, but adjuvant chemotherapy and radiotherapy have no significant effect on 5-year survival. Although there is no consensus on treatment regimens, it is concluded that more comprehensive studies should be conducted in a larger sample.