Breast Cancer Cases Research Articles

Abstract LB328: Measurement of ER and Ki67 coexpression in cytokeratin positive epithelial cells in benign breast disease (BBD) percutaneous biopsies

Abstract Over 1 million women in the U.S. undergo radiologically guided percutaneous biopsies annually. Of these, 75% reveal benign breast disease (BBD), typically surrounded by normal breast lobules, which are proposed to reflect the biology of the breast parenchyma diffusely. With aging, normal lobules undergo involution, and delays in this process are linked to increased breast cancer (BC) risk. Because BBD patients are at increased risk of developing BC, and pathologic classification only stratifies risks among groups of patients, novel methods for individual BC risk prediction are needed to guide precision management. Prior literature has shown that most proliferating epithelial cells in normal lobules do not express estrogen receptor (i.e., ER-/Ki67+), whereas co-expression is frequent in BC precursors and in BCs (i.e., ER+/Ki67+). Thus we developed and applied a novel quantitative dual ER/Ki67 stain to BBD biopsies from the well-characterized contemporary Mayo Clinic BBD cohort (2002-2013) to assess differences by levels of lobular involution and tissue type (BBD vs. normal), as well as associations with BC risk. We identified 100 BBD biopsies preceding BC (cases) and 100 biopsies from cancer-free women (controls), frequency-matched on age and length of follow-up. A multiplex immunofluorescence assay was developed to detect ER/Ki67 coexpression in cytokeratin positive epithelial cells in normal lobules or BBD lesions in FFPE tissue sections. An inverse normal transformation was applied to cell counts and proportions and associations were assessed for levels of lobular involution, tissue type (normal lobule vs. BBD), and case status using t-tests and linear regression models. The final data set included 1152 normal lobules or BBD lesions in biopsies of 177 subjects (88 cases and 89 controls). In univariate analyses, normal lobules showing delayed age related involution included higher counts of ER-/Ki67+, ER+/Ki67- and ER+/Ki67+ cells, and the lowest proportion of ER+/Ki67- cells (p<0.03; all). In separate analyses comparing presence vs. absence, detection of any ER+/Ki67+ cells was suggestively more common in non-involuted vs. involuted lobules. Compared with normal lobules, BBD showed higher counts and proportions of ER+/Ki67- and ER+/Ki67+ cells and lower values for ER-/Ki67+ (all p<0.001). In these preliminary results, marker expression in normal lobules and in BBD did not differ by case-control status. Preliminarily, we find that ER+/Ki67+ cells are increased in normal lobules with delayed age-related involution and in BBD lesions, consistent with their associations with increased BC risk. These findings are consistent with the risk reducing effects of endocrine chemoprevention and may serve as useful biomarkers in prevention therapy. In this analysis, limited to only a few lobules and BBD lesions per biopsy, ER+/Ki67+ cell counts and proportions did not vary significantly by case-control status. Citation Format: Melody L. Stallings-Mann, Robert A. Vierkant, Stacey J. Winham, Bryan McCauley, Matt R. Jensen, Sophie Noel, Laura Pacheco-Spann, Celine M. Vachon, Amy C. Degnim, Derek C. Radisky, Mark E. Sherman. Measurement of ER and Ki67 coexpression in cytokeratin positive epithelial cells in benign breast disease (BBD) percutaneous biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB328.

Impact of neoadjuvant chemotherapy on the safety and long-term outcomes of patients undergoing immediate breast reconstruction after mastectomy

BackgroundIn breast cancer patients receiving neoadjuvant chemotherapy (NAC), immediate breast reconstruction (IBR) as a breast cancer treatment option remains controversial. We assessed the impact of NAC on surgical and oncological outcomes of patients undergoing IBR.MethodsThis was a retrospective multicenter study of 4726 breast cancer cases undergoing IBR. The rate of postoperative complications and survival data were compared between IBR patients who received NAC and those who did not receive NAC. Propensity score matching analysis was performed to mitigate selection bias for survival.ResultsOf the total 4726 cases, 473 (10.0%) received NAC. Out of the cases with NAC, 96 (20.3%) experienced postoperative complications, while 744 cases (17.5%) without NAC had postoperative complications. NAC did not significant increase the risk of complications after IBR (Odds ratio, 0.96; 95%CI 0.74–1.25). At the median follow-up time of 76.5 months, 36 patients in the NAC group and 147 patients in the control group developed local recurrences. The 5-year local recurrence-free survival rate was 93.1% in the NAC group and 97.1% in the control group. (P < 0.001). After matching, there was no significant difference between the two groups.ConclusionIBR after NAC is a safe procedure with an acceptable postoperative complication profile.

Suppression of AGRN enhances CD8+ T cell recruitment and inhibits breast cancer progression.

Breast cancer (BC) stands as a prominent contributor to global cancer-related mortality, with an increasing incidence annually. This study aims to investigate AGRN gene expression in BC, as well as explore its influence on the tumor immune microenvironment. AGRN displayed a pronounced upregulation in BC tissues relative to paracancerous tissues. Single-cell RNA analysis highlighted AGRN-specific elevation within cancer cell clusters and also showed expression expressed in stromal as well as immune cell clusters. AGRN upregulation was positively correlated with clinicopathological stage and negatively correlated with BC prognosis. As revealed by the invitro experiment, AGRN knockdown effectively hinders BC cells in terms of proliferation, invasion as well as migration. AGRN protein, which may interact with EXT1, LRP4, RAPSN, etc., was primarily distributed in the cell cytoplasm. Notably, immune factors might interact with AGRN in BC, evidenced by its discernible associations with immunofactors like IL10, CD274, and PVRL2. Mass spectrometry and immunohistochemistry revealed that the reduction of AGRN led to an increase in CD8+ T cells with triple-negative breast cancer (TNBC). Mechanistically, the connection between TRIM7 and PD-L1 is improved by AGRN, acting as a scaffold, thereby facilitating the accelerated degradation of PD-L1 by TRIM7. Downregulation of AGRN inhibits BC progression and increases CD8+ T cell recruitment. Targeting AGRN may contribute to BC treatment. The biomarker AGRN, serving as a therapeutic target for BC, emerges as a prospective avenue for enhancing both diagnosis and prognosis in BC cases.

Proteomic and metabolomic characterization of bone, liver, and lung metastases in plasma of breast cancer patients.

Breast cancer (BC) is the second leading cause of cancer-related deaths among women, primarily due to metastases to other organs rather than the primary tumor. In this study, a comprehensive analysis of plasma proteomics and metabolomics was conducted on a cohort of 51 BC patients. Potential biomarkers were screened by the Least Absolute Shrinkage and Selection Operator (LASSO) regression and Random Forest algorithm. Additionally, enzyme-linked immunosorbent assay (ELISA) kits and untargeted metabolomics were utilized to validate the prognostic biomarkers in an independent cohort. In the study, extracellular matrix (ECM)-related functional enrichments were observed to be enriched in BC cases with bone metastases. Proteins dysregulated in retinol metabolism in liver metastases and leukocyte transendothelial migration in lung metastases were also identified. Machine learning models identified specific biomarker panels for each metastasis type, achieving high diagnostic accuracy with area under the curve (AUC) of 0.955 for bone, 0.941 for liver, and 0.989 for lung metastases. For bone metastasis, biomarkers such as leucyl-tryptophan, LysoPC(P-16:0/0:0), FN1, and HSPG2 have been validated. dUDP, LPE(18:1/0:0), and aspartylphenylalanine have been confirmed for liver metastasis. For lung metastasis, dUDP, testosterone sulfate, and PE(14:0/20:5) have been established.

Ensemble Learning Approach Reveals Significant Clinical Attributes from Real-World Breast Cancer Cases

Breast cancer has become on of the leading causes of death in Indonesia. This study contributes to global efforts to combat breast cancer by improving patient outcome prediction accuracy. This study employed ensemble learning techniques such as Random Forest, XGBoost, and LightGBM. The results of the study demonstrates LightGBM's superior performance (accuracy=85%, ROC-AUC=81%, AUPR=85%). Notably, all three algorithms identify key clinical attributes: "Relapse Free Status (Months)", "Overall Survival (Months)", "Nottingham Prognostic Index", and "Lymph Nodes Examined Positive". LightGBM uniquely highlights "pam50_LumA" as significant, suggesting reduced fatality risk for Luminal A subtype patients, while others prioritize "Tumor Size". This research lays groundwork for intelligent systems to predict breast cancer outcomes, potentially transforming patient care and clinical practice.

AN AUTOMATED BREAST CANCER DETECTION BY HEURISTIC-BASED ENSEMBLE DEEP CLASSIFIER USING MAMMOGRAM AND TOMOSYNTHESIS IMAGES

Nowadays, breast cancer is the most founded cancer among women. Moreover, 2.3 million new cases of breast cancer have been detected among women since 2020 as reported by World Health Organization (WHO). Many research studies based on breast cancer mainly aim at ultrasound, mammography, and Magnetic Resonance Images (MRI). However, there exist certain limitations such as lack of access for the detection of disease in rural and remote cities and insufficient knowledge about the availability of computer-aided systems. In order to overcome the problem, it is necessary to develop an effective detection model for breast cancer. For the experimentation, the input images like mammogram images and tomosynthesis images are garnered from the benchmark online resources. The input image further undergoes the pre-processing stage, which is made by using “Contrast Limited Adaptive Histogram Equalization (CLAHE) and histogram equalization (HE)”. Then, the pre-processed images are further given as input to the segmentation, in which deeplabv3 is deployed. Consequently, with the assistance of segmented images, the relevant features like “texture features, color features, shape features, deep features, statistical features and morphological features” are extracted. Then, these obtained features are used in weighted feature selection, where the optimal feature selection is performed, and weights are optimized by the Enhanced Adaptive Prey Location-Based Pelican Optimization Algorithm (APL-POA). Finally, the weighted accurate features are given as input to the Ensemble Deep Learning (EDC) model. The ensemble model is structured by “Deep Neural Network (DNN), Recurrent Neural Network (RNN), Bidirectional Long Short-Term Memory (Bi-LSTM), Deep Temporal Convolution Networks (DTCN) and Gated Recurrent Unit (GRU)”, in which the hyperparameters of every classifier are smoothened optimally by the enhanced APL-POA algorithm. Through the experimental analysis, the proposed work tends to provide an improved classification rate and rapid detection of disease that aids in better diagnosis of the patients.

Organizational Breast Cancer Data Mart: A Solution for Assessing Outcomes of Imaging and Treatment.

In the United States, a comprehensive national breast cancer registry (CR) does not exist. Thus, care and coverage decisions are based on data from population subsets, other countries, or models. We report a prototype real-world research data mart to assess mortality, morbidity, and costs for breast cancer diagnosis and treatment. With institutional review board approval and Health Insurance Portability and Accountability Act (HIPPA) compliance, a multidisciplinary clinical and research data warehouse (RDW) expert group curated demographic, risk, imaging, pathology, treatment, and outcome data from the electronic health records (EHR), radiology (RIS), and CR for patients having breast imaging and/or a diagnosis of breast cancer in our institution from January 1, 2004, to December 31, 2020. Domains were defined by prebuilt views to extract data denormalized according to requirements from the existing RDW using an export, transform, load pattern. Data dictionaries were included. Structured query language was used for data cleaning. Five-hundred eighty-nine elements (EHR 311, RIS 211, and CR 67) were mapped to 27 domains; all, except one containing CR elements, had cancer and noncancer cohort views, resulting in a total of 53 views (average 12 elements/view; range, 4-67). EHR and RIS queries returned 497,218 patients with 2,967,364 imaging examinations and associated visit details. Cancer biology, treatment, and outcome details for 15,619 breast cancer cases were imported from the CR of our primary breast care facility for this prototype mart. Institutional real-world data marts enable comprehensive understanding of care outcomes within an organization. As clinical data sources become increasingly structured, such marts may be an important source for future interinstitution analysis and potentially an opportunity to create robust real-world results that could be used to support evidence-based national policy and care decisions for breast cancer.

Cost-effectiveness of BRCA1 testing at time of obstetrical prenatal carrier screening for cancer prevention

BackgroundImproved technologies paired with an increase in access to genetic testing has led to the availability of expanded carrier screening evaluating hundreds of disorders. Currently, most autosomal dominant mutations, such as BRCA1, are not included in expanded carrier assays. Screening pregnant or preconception reproductive-aged women for BRCA1 may present a unique opportunity to perform population-based screening for patients at a time where precancer screening, chemoprevention and/or risk reducing surgery may be beneficial. ObjectiveThe objective of our study was to inform clinical decision making as to whether the universal incorporation of BRCA1 testing at the time of obstetrical prenatal carrier screening is cost-effective. Study DesignA decision analysis and Markov model was created. The initial decision point in the model was BRCA1 testing at the time of expanded carrier screening. Model probabilities, cost, and utility values were derived from published literature. For BRCA1-positive patients, the model simulated breast cancer screening and risk-reducing surgical interventions. A cycle length of 1 year and a time horizon of 47 years was used to simulate the lifespan of patients. Setting was Obstetrical clinics in U.S., and Participants were a theoretical cohort of 1,429,074 pregnant patients who annually undergo expanded carrier screening. ResultsAmong our cohort, BRCA1 testing resulted in identification of an additional 3,716 BRCA1 patients, prevention of 1,394 breast and ovarian cancer cases, and 1,084 fewer deaths. BRCA1 testing was a cost-effective strategy compared to no BRCA1 testing with an ICER of $86,001/QALYs. In a one-way sensitivity analysis, we varied the prevalence of BRCA1 in the population from 0% up to 20% and found that BRCA1 testing continued to be the cost-effective strategy until prevalence rate was reduced to 0.16% (Table S1). Multiple additional sensitivity analyses did not substantially impact the cost-effectiveness. ConclusionThe addition of BRCA1 testing to obstetrical prenatal carrier screening is a cost-effective management strategy to identify at-risk women at a time when cancer screening and preventive strategies can be effective. Despite the burden of additional genetic counseling, prenatal care represents a unique opportunity to implement population-based genetic testing.

Screening Mammography for Males With Elevated Breast Cancer Risk, Mutation Carriers, and Gynecomastia

IntroductionThe recommendations for annual mammography for male carriers with gynecomastia are controversial. This study investigated the potential link between gynecomastia and breast cancer in male carriers. Patients and MethodsThe database of a tertiary medical center was retrospectively searched for all male patients who underwent at least 1 digital mammography study from 2016 to 2023. Known carriers of a pathogenic variant in a high-risk breast-cancer gene were identified. Patients were stratified by carrier status, diagnosis of breast cancer, and diagnosis of gynecomastia. Data on demographics, hormone profile, and pathology results were compared. ResultsThe cohort included 446 men of whom 82 were known carriers. Gynecomastia was diagnosed by mammography in 251 patients: 239/364 noncarriers (66%) and 12/82 carriers (15%) (P < .0001). Breast cancer was found in 21/364 noncarriers (6%) and 6/82 carriers (7%) (P < .6), and in 10/251 patients with gynecomastia (4%) and 17/193 (9%) without gynecomastia (P < .05). Among patients without gynecomastia, the number of breast cancer cases was similar in carriers and noncarriers (P = .3). Among patients with gynecomastia, the rate of breast cancer was higher in carriers (P < .08). On logistic regression analysis, the effect of gynecomastia on carriers was significant (P = .02). The odds ratio for a breast cancer diagnosis was 5.8 in the presence of gynecomastia (95% CI, 1.1-31, P < .04) and 0.52 in the absence of gynecomastia (95% CI, 0.2-1.7, P < .3). ConclusionGynecomastia may be associated with an increased risk of breast cancer in carriers. Larger studies are needed to determine whether and when to screen male carriers.

Ultrasonography is an effective tool for breast cancer screening in individuals with severe motor and intellectual disabilities.

Individuals with severe motor and intellectual disabilities have become an aging population, and high cancer morbidity and mortality are critical issues affecting their survival. Cancer screening is a crucial method of resolving this issue; however, a suitable screening method for them has not been established. We used ultrasonography alone and performed breast cancer screening for women over 30 years old in our facility from 2016 to 2023. We observed the outcomes and calculated the recall/detection rate in this screening. Three cases among 379 tested positive in this screening, all of which underwent radical surgery. They are alive and well without relapse present. We detected these breast cancer cases with a low recall rate. We were able to successfully detect breast cancer cases using ultrasonography alone. Ultrasonography is an effective and feasible tool for breast cancer screening in individuals with severe motor and intellectual disabilities.

396 Unraveling the Immunological Basis of Lobular Involution in Breast Cancer Development

OBJECTIVES/GOALS: Reveal common immune mechanisms in dysregulated age-related lobular involution (ARLI) and post-partum lobular involution (PPLI) to understand their link to increased breast cancer risk, challenging the traditional view of their distinctiveness. Ultimately, to improve breast cancer risk assessment and personalized prevention METHODS/STUDY POPULATION: The Mayo Clinic Benign Breast Disease (BBD) cohort comprises of ~20,000 women with benign biopsies, including ~1000 women with sequential benign biopsies. Lobular involution (LI) status was assessed by selecting perimenopausal women, ages 45-55, with sequential biopsies, comparing acini number and lobule size between initial and subsequent biopsies. NanoString IO360/ BC360 RNA profiling identified differentially expressed genes associated with dysregulated LI. Using multiplex immunofluorescence (mIF), I'll analyze and spatially map immune biomarkers related to dysregulated ARLI and PPLI in BBD tissue from perimenopausal women who did or did not go on to develop breast cancer, assessing the commonality of ARLI and PPLI markers and exploring their potential as risk biomarkers for breast cancer. RESULTS/ANTICIPATED RESULTS: Preliminary findings link patients who display dysregulated ARLI with an increased breast cancer risk and identify vital PPLI biomarkers in perimenopausal women. I expect the biopsies of women who developed post-menopausal breast cancer (PMBC) and post-partum breast cancer (PPBC) to exhibit elevated levels of dysregulated ARLI immune biomarkers and PPLI biomarkers. Spatially mapping these markers promises to provide a more comprehensive understanding of their interactions, potentially revealing common immunological pathways. These findings could transform our current paradigm of ARLI and PPLI as distinct processes and demonstrate their interconnection in shaping breast cancer risk. DISCUSSION/SIGNIFICANCE: PMBC and PPBC dominate majority of breast cancer cases. Both involve activation of the understudied process of lobular involution, which has been shown to have pro-tumorigenic traits. Elucidating these mechanisms will aid more efficient risk stratification and personalized prevention to reduce incidence and mortality of breast cancer.

CircRNA circRREB1 promotes tumorigenesis and progression of breast cancer by activating Erk1/2 signaling through interacting with GNB4

Current investigations have illuminated the essential roles played by circular RNAs (circRNAs) in driving breast cancer (BC) tumorigenesis. However, the functional implications and molecular underpinnings of most circRNAs in BC are not well characterized. Here, Circular RNA (circRNA) expression profiles were analyzed in four surgically resected BC cases along with adjacent non-cancerous tissues applying RNA microarray analysis. The levels and prognostic implications of circRREB1 in BC were subjected to quantitative real-time PCR (qRT-PCR) and in situ hybridization (ISH). Experimental manipulation of circRREB1 levels in both in vivo and in vitro settings further delineated its role in BC cell growth, invasion, and metastasis. The mechanical verification of circRREB1's interaction with GNB4 was established through RNA pull-down, mass spectrometry, Western blot analysis, RNA immunoprecipitation assays (RIP), fluorescence ISH (FISH), and rescue experiments. We found that circRREB1 exhibited significant upregulation in BC tissues and cells, implicating its association with an unfavorable prognosis in BC patients. CircRREB1 knockdown elicited anti-proliferative, anti-migratory, anti-invasive, and pro-apoptotic effects in BC cells, whereas its upregulation exerted opposing influences. Follow-up mechanistic examinations suggested that circRREB1 might interact with GNB4 directly, inducing the activation of Erk1/2 signaling and driving BC progression. Our findings collectively indicate that the interplay of circRREB1 with GNB4 promotes Erk1/2 signaling, thereby fostering BC progression, and positioning circRREB1 as a candidate therapeutic target for intervention in BC.

CASE REPORT OF CARCINOMA OF BREAST

Breast cancer occurs more frequently in the left breast than the right. The left breast is 5%-10% more likely to develop cancer than the right breast. 1 in 8 U.S. women (about 12%) will develop invasive breast cancer over the course of her lifetime. In 2020, an estimated 276,480 new cases of invasive breast cancer are expected to be diagnosed in women in the U.S., along with 48,530 new cases of non-invasive (in situ) breast cancer. About 2,620 new cases of invasive breast cancer are expected to be diagnosed in men in 2020,[1].

A Scoping Review of the Knowledge and Practice of Breast Self-Examination among Women in Nigeria

Over 19 million cases of breast cancer were reported among women in 2020, surpassing lung cancer to become the leading cause of cancer worldwide. Women in developing countries have higher mortality rates than women in developed countries. Breast self-examination (BSE) is a simple procedure carried out by women themselves to determine any changes in their breasts and if needed seek further medical attention. This scoping review aimed to assess the available evidence on the knowledge and practice of BSE among women in Nigeria. This scoping review was conducted by searching African Journals On-Line (AJOL), ProQuest, PubMed and Science Direct databases for eligible studies. The relevant data was then extracted and a summary of the findings reported. 36 eligible articles were identified, 15 studies met the inclusion criteria and were considered for data extraction. All the studies included were cross-sectional descriptive surveys. The average reported knowledge of BSE is 67%, with 40% of study respondents practicing BSE, but only 26% of study respondents practiced BSE monthly. There’s low practice of BSE among women in Nigeria. Further research and appropriate interventions are needed to improve early detection and treatment of breast cancer.

Predictive Mathematical Model on Breast Cancer : AStudy

In the present study, we have designed a mathematical model to analyze whether the cases of breast cancer are maximized or minimized in Madhya Pradesh. Especially to check the age range in which it’s more susceptible to the disease and its means of therapy. The important data collected from Jawaharlal Nehru Cancer Hospital, Bhopal (JLNCH) and Gandhi Medical College, Bhopal (GMC) is from over ten years of reviews of the cases. Actual documentary and analytical methods were used to collect and analyze the data. It is concluded from the results that the number of cancer cases is increasing in both hospitals; its projection may reach up to 97.8% by the year 2023; the age range of 40–50 is more vulnerable to the disease. The line of treatment for breast cancer patients is surgery, chemotherapy, and radiotherapy in both hospitals.

An audit of breast cancer in patients 40 years and younger in two Johannesburg academic hospitals.

Breast cancer is the most common cancer in females, usually diagnosed after the age of 50 years. There is a perceived increase in breast cancer cases in young women in two public sector Johannesburg academic hospitals; however, there is a shortage of data to confirm this. This study aimed to assess data on breast cancer in young patients and determine any increase in the number of cases in patients 40 years and younger. A retrospective analysis of radiology and histopathology reports of patients 40 years and younger, seen at the radiology departments of two Johannesburg academic hospitals, was performed over a 5-year period. The frequency, histology and immunohistochemical results of breast cancer diagnoses were determined in patients with a Breast Imaging - Reporting and Data System (BI-RADS) classification of 4 or above. Breast cancer was diagnosed in 73% of the total eligible 469 patients. The mean patient age was 34.35 years. Invasive ductal carcinoma was diagnosed in 83% (n = 283) of patients classified as BI-RADS 5 on imaging. Luminal A and B subtypes were the most common. The highest number of patients (n = 142) were seen in 2016 of which 92 had breast cancer. In this very specific sample set, there was a lower number of breast cancer diagnoses in 2015 and then an increase of breast cancer diagnoses in young patients from 2016 to 2018. Earlier breast cancer detection benefits the patient, their families and their reproductive ability. Knowledge of breast cancers in young patients can increase awareness, leading to effective, early diagnoses.

Augmenting the Antitumor Efficacy of Natural Killer Cells via SynNotch Receptor Engineering for Targeted IL-12 Secretion.

Natural killer (NK) cells are crucial components of innate immunity, known for their potent tumor surveillance abilities. Chimeric antigen receptors (CARs) have shown promise in cancer targeting, but optimizing CAR designs for NK cell functionality remains challenging. CAR-NK cells have gained attention for their potential to reduce side effects and enable scalable production in cancer immunotherapy. This study aimed to enhance NK cell anti-tumor activity by incorporating PD1-synthetic Notch (synNotch) receptors. A chimeric receptor was designed using UniProt database sequences, and 3D structure models were generated for optimization. Lentiviral transduction was used to introduce PD1-Syn receptors into NK cells. The expression of PD1-Syn receptors on NK cell surfaces was assessed. Engineered NK cells were co-cultured with PDL1+ breast cancer cells to evaluate their cytotoxic activity and ability to produce interleukin-12 (IL-12) and interferon-gamma (IFNγ) upon interaction with the target cells. This study successfully expressed the PD1-Syn receptors on NK cells. CAR-NK cells secreted IL-12 and exhibited target-dependent IFNγ production when engaging PDL1+ cells. Their cytotoxic activity was significantly enhanced in a target-dependent manner. This study demonstrates the potential of synNotch receptor-engineered NK cells in enhancing anti-tumor responses, especially in breast cancer cases with high PDL1 expression.

Triple-negative occult breast cancer: A case report

The phenomenon of occult breast cancer represents a rare scenario raising crucial questions regarding its clinical presentation, diagnosis, and timely treatment. The therapeutic challenge can become even more difficult in the specific case of triple-negative breast cancer. This article presents the case report of a patient who had a palpable axillary nodule during a routine gynecological exam. A core needle biopsy confirmed that the patient had metastatic ductal carcinoma of mammary origin, which was triple-negative. Despite several diagnostic procedures, there was no evidence of a primary tumor in the breast clinically or in imaging studies. The patient underwent neoadjuvant chemotherapy with satisfying outcomes and later, to radical surgery therapy regardless of the feasibility of receiving a conservative treatment.

Adherence to HEI-2010 and odds of breast cancer according to the menopause status: Evidence from Middle Eastern Country.

Majority of earlier studies have assessed the association between individual healthy eating index-2010 (HEI-2010) and the odds of breast cancer (BC). However, no study has been conducted on the effect of compliance with HEI-2010 and the odds of BC in the Iranian population with a large sample size. Therefore, we aimed to investigate the relationship between the HEI-2010 and the odds of BC in the Iranian population. This population-based case-control study included 350 newly diagnosed cases of BC and 700 healthy controls randomly selected from adult women. HEI-2010 was examined using validated questionnaires. The adherence to HEI-2010 among the participants was divided into four categories. The general characteristics of the participants in the quartiles of the HEI score for categorical variables and continuous variables were evaluated using chi-square and one-way analysis of variance, respectively. Also, using logistic regression analysis, dietary intakes were evaluated in HEI score quartiles. Also, confounding variables were adjusted in different models. People with the highest HEI score had 60% lower odds of BC (OR: 0.40; 95% CI: 0.27, 0.57) than those with the lowest score among post-menopause women. After controlling for age and energy intake, individuals with the highest HEI score were 78% less likely to have BC compared with those with the lowest score (OR: 0.22; 95% CI: 0.14, 0.33). Adjustments for other potential confounders including demographic factors made the association stronger (OR: 0.21; 95% CI: 0.13, 0.32). This association remained significant even after taking BMI into model (OR: 0.27; 95% CI: 0.17, 0.43). Finally, in this study we found an association between HEI-2010 and odds of breast cancer. This association was particularly seen in postmenopausal women. No significant association was found between adherence to HEI-2010 and odds of BC among pre-menopausal.

Therapeutic significance of long noncoding RNAs in estrogen receptor-positive breast cancer.

About 70% of cases of breast cancer are compromised by Estrogen-positive breast cancer. Through its regulation of several processes, including cell proliferation, cell cycle progression, and apoptosis, Estrogen signaling plays a pivotal role in the genesis and progression of this particular kind of breast cancer. One of the best treatment strategies for treating Estrogen-positive breast cancer is blocking Estrogen signaling. However, patients' treatment failure is mainly caused by the emergence of resistance and metastases, necessitating the development of novel therapeutic targets. Numerous studies have shown long noncoding RNAs (lncRNAs) to play a role in Estrogen-mediated carcinogenesis. These lncRNAs interact with co-regulators and the Estrogen signaling cascade components, primarily due to Estrogen activation. Vimentin and E-cadherin are examples of epithelial-to-mesenchymal transition markers, and they regulate genes involved in cell cycle progression, such as Cyclins, to affect the growth, proliferation, and metastasis of Estrogen-positive breast cancer. Furthermore, a few of these lncRNAs contribute to developing resistance to chemotherapy, making them more desirable targets for enhancing results. Thus, to shed light on the creation of fresh approaches for treating this cancer, this review attempts to compile recently conducted studies on the relationship between lncRNAs and the advancement of Estrogen-positive breast cancer.