Benign Breast Disease Research Articles

Associations of Early-Life and Adult Anthropometric Measures with the Expression of Stem Cell Markers CD44, CD24, and ALDH1A1 in Women with Benign Breast Biopsies.

According to the stem cell hypothesis, breast carcinogenesis may be related to the breast stem cell pool size. However, little is known about associations of breast cancer risk factors, such as anthropometric measures, with the expression of stem cell markers in noncancerous breast tissue. The analysis included 414 women with biopsy-confirmed benign breast disease in the Nurses' Health Study and Nurses' Health Study II. Birthweight, weight at age 18, current weight, and current height were reported via self-administered questionnaires. IHC staining of stem cell markers (CD44, CD24, and aldehyde dehydrogenase family 1 member A1) in histopathologically normal epithelial and stromal breast tissue was quantified using an automated computational image analysis system. Linear regression was used to examine the associations of early-life and adult anthropometric measures with log-transformed stem cell marker expression, adjusting for potential confounders. Birthweight [≥10.0 vs. <5.5 lbs: β (95% confidence interval) = 4.29 (1.02, 7.56); P trend = 0.001 in the stroma] and adult height [≥67.0 vs. <63.0 inch: 0.86 (0.14, 1.58); P trend = 0.02 in the epithelium and stroma combined] were positively associated with CD44 expression. Childhood body fatness was inversely associated (P trend = 0.03) whereas adult height was positively associated with CD24 expression in combined stroma and epithelium (P trend = 0.03). Our data suggest that anthropometric measures, such as birthweight, adult height, and childhood body fatness, may be associated with the stem cell expression among women with benign breast disease. Anthropometric measures, such as birthweight, height, and childhood body fatness, may have long-term impacts on stem cell population in the breast.

Multiplex Digital Spatial Profiling in Breast Cancer Research: State-of-the-Art Technologies and Applications across the Translational Science Spectrum.

While RNA sequencing and multi-omic approaches have significantly advanced cancer diagnosis and treatment, their limitation in preserving critical spatial information has been a notable drawback. This spatial context is essential for understanding cellular interactions and tissue dynamics. Multiplex digital spatial profiling (MDSP) technologies overcome this limitation by enabling the simultaneous analysis of transcriptome and proteome data within the intact spatial architecture of tissues. In breast cancer research, MDSP has emerged as a promising tool, revealing complex biological questions related to disease evolution, identifying biomarkers, and discovering drug targets. This review highlights the potential of MDSP to revolutionize clinical applications, ranging from risk assessment and diagnostics to prognostics, patient monitoring, and the customization of treatment strategies, including clinical trial guidance. We discuss the major MDSP techniques, their applications in breast cancer research, and their integration in clinical practice, addressing both their potential and current limitations. Emphasizing the strategic use of MDSP in risk stratification for women with benign breast disease, we also highlight its transformative potential in reshaping the landscape of breast cancer research and treatment.

A prospective cross-sectional observational comparative study: evaluating palpable breast lumps through comparative analysis of sonomammography breast imaging reporting and data system scores and fine needle aspiration cytology

This study protocol outlines a prospective cross-sectional observational investigation aimed at assessing the correlation between Sonomammography Breast Imaging Reporting and Data System (BI-RADS) scores and Fine-Needle Aspiration Cytology (FNAC) findings in diagnosing benign and malignant palpable breast lumps among patients admitted to AVBRH. The primary objective is to understand the diagnostic accuracy of FNAC and Sonomammography BI-RADS scoring in identifying breast lumps’ nature. Four specific objectives guide this study: 1) To determine the diagnostic accuracy of FNAC; 2) To evaluate the diagnostic precision of Sonomammography BI-RADS scores; 3) To compare the diagnostic outcomes of sonomammography and FNAC with HPE, and 4) To examine the age-wise distribution of benign and malignant palpable breast diseases. The study will be conducted at AVBRH, Sawangi (Meghe), Wardha, over three years, commencing in June 2022. The anticipated findings from this study will significantly contribute to refining the diagnostic strategies for palpable breast lumps, enhancing patient care and decision-making.

Involvement of FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p in breast cancer.

FAM170B-AS1 is usually expressed low in all organs except for testicular tissues. No study was performed to explore its role in breast cancer (BC). Contradictory results were reported about hsa-miR-1202 and hsa-miR-146a-5p in BC. The present study aimed to explore the involvement of FAM170B-AS1 in BC using bioinformatics predictive tools, followed by a practical validation besides exploring the impact of hsa-miR-1202 and hsa-miR-146a-5p in BC. This study enrolled 96 female patients with BC, 30 patients with benign breast diseases (BBD), and 25 control subjects. The expressions of circulating FAM170B-AS1, hsa-miR-1202, and hsa-miR-146a-5p were quantified using qRT-PCR. These ncRNAs' associations, predictive, and diagnostic roles in BC were statistically tested. The underlying miRNA/mRNA targets of FAM170B-AS1 in BC were bioinformatically predicted followed by confirmation based on the GEPIA and TCGA databases. The expression of FAM170B-AS1 was upregulated in sera of BC patients and hsa-miR-1202 was upregulated in sera of BBD and BC patients while that of hsa-miR-146a-5p was downregulated in BC. These FAM170B-AS1 was significantly associated with BC when compared to BBD. FAM170B-AS1 and hsa-miR-1202 were statistically associated with the BC's stage, grade, and LN metastasis. FAM170B-AS1 and hsa-miR-146a-5p gave the highest specificity and sensitivity for BC. KRAS and EGFR were predicted to be targeted by FAM170B-AS1 through interaction with hsa-miR-143-3p and hsa-miR-7-5p, respectively. Based on the TCGA database, cancer patients having mutations in FAM170B show good overall survival. The present study reported that for the first time, FAM170B-AS1 may be a potential risk factor, predictive, and diagnostic marker for BC. In addition, FAM170B-AS1 might be involved in BC by interacting with hsa-miR-143-3p/KRAS and hsa-miR-7-5p/EGFR through enhancement or repression that may present a new therapeutic option for BC.

Searching for a twinkling artefact in breast microcalcifications using B-flow ultrasonic non-doppler technology: a prospective study

INTRODUCTION: The rapid rejuvenation of breast cancer in recent years has made it necessary to look for non-X-ray methods of imaging microcalcifications in women not yet covered by mammography screening. Developing technologies to see these microcalcifications on ultrasound is a promising goal, potentially reducing the number of unnecessary biopsies.OBJECTIVE: Evaluation of factors influencing the ability of the B-flow technique to detect the presence of a flickering artifact in patients with microcalcifications detected by mammography.MATERIALS AND METHODS: A prospective study of 57 patients with microcalcifications detected on mammograms was conducted. The Nondoppler technology of B-flow ultrasound examination was used for targeted ultrasound with the search for these areas during ultrasound. The possibilities of visualization of the twinkle artifact were evaluated for various microcalcifications in size, distribution, their number, and for pathological processes of different nature. Images in B-flow mode were found to be positive when a bright local flash occurred against a dark background in B-mode. Verification of diagnostic findings was performed by ultrasound-guided core- biopsy from areas with a twinkle artifact (in the presence of an imaging area during ultrasound) or with stereotactic biopsy (in the absence of visualization of the suspicious area with ultrasound with B-flow).Statistics: The ANOVA test was used for triple pairwise comparisons between positive groups. The p&lt;0.05 value was considered statistically significant.RESULTS: According to the results of the study, out of 57 cases with microcalcifications, 34 (60%) recorded a twinkle artifact. The amount of microcalcifications with a visualized twinkle effect in B-flow was significantly higher in benign processes 34 (82.9%) out of 41, and less often in malignant 8 (50%) out of 16 (p=0.035). The effect of calcification morphology on the mammogram on their detection by ultrasound in the B-flow mode (p=0.035) was statistically significant. The most frequently manifested twinkle artifact were rounded, regular-shaped calcifications in 19 (95%) out of 20, which were found in granulomatous mastitis, fibrocystic changes, fibroadenomas, sclerosing adenosis, as well as polymorphic calcifications in 7 (63.6%) of 11. In the B-flow mode, it was not possible to obtain a twinkle artifact mainly with point small calcifications of 9 (69.2%) out of 13, and in all cases with linear or linear branching calcifications. In amorphous microcalcifications, the characteristics of background echogenicity and the presence or absence of a nodal component in the gray scale mode had a much greater influence on the appearance of the twinkle effect in the normal B-mode, whereas in the B-flow mode, these characteristics did not have a decisive effect on the appearance of a flickering artifact (p=0.8). The density of distribution of microcalcifications, the size of calcifications, the final pathomorphology, mammography characteristics, the background environment during ultrasound by the presence or absence of nodular formation and anechoic zones, did not affect the appearance of a bright flash in the B-flow mode.DISCUSSION: The density of calcification distribution was not decisive for the appearance of a shimmering artifact in the B-flow mode. The flicker artifact is recorded both in grouped microcalcifications and in single ones. B-flow can help to detect calcifications that are not visible in the usual B-flow mode due to the lack of pronounced tissue contrast. But this artifact cannot be used to differentiate between benign and malignant processes.CONCLUSION: The B-flow technique is promising for clarifying the twinkle artifact in the detected microcalcifications on the mammogram, which could potentially increase the incidence of ultrasound-guided trephine biopsies by detecting more areas with microcalcification accumulations.

Serum protein profiling reveals an inflammation signature as a predictor of early breast cancer survival

BackgroundBreast cancers exhibit considerable heterogeneity in their biology, immunology, and prognosis. Currently, no validated, serum protein-based tools are available to evaluate the prognosis of patients with early breast cancer.MethodsThe study population consisted of 521 early-stage breast cancer patients with a median follow-up of 8.9 years. Additionally, 61 patients with breast fibroadenoma or atypical ductal hyperplasia were included as controls. We used a proximity extension assay to measure the preoperative serum levels of 92 proteins associated with inflammatory and immune response processes. The invasive cancers were randomly split into discovery (n = 413) and validation (n = 108) cohorts for the statistical analyses.ResultsUsing LASSO regression, we identified a nine-protein signature (CCL8, CCL23, CCL28, CSCL10, S100A12, IL10, IL10RB, STAMPB2, and TNFβ) that predicted various survival endpoints more accurately than traditional prognostic factors. In the time-dependent analyses, the prognostic power of the model remained rather stable over time. We also developed and validated a 17-protein model with the potential to differentiate benign breast lesions from malignant lesions (Wilcoxon p < 2.2*10− 16; AUC 0.94).ConclusionsInflammation and immunity-related serum proteins have the potential to rise above the classical prognostic factors of early-stage breast cancer. They may also help to distinguish benign from malignant breast lesions.

RAPID ON-SITE EVALUATION AND MICRONUCLEUS SCORING IN BREAST LESIONS FINE NEEDLE ASPIRATION CYTOPATHOLOGY BY NEW IAC YOKOHAMA SYSTEM OF REPORTING

Objective: The objective of the study is to report all fine needle aspiration cytopathology (FNAC) cases of lump breast as per New Yokohama classification 2016, to highlight the importance of rapid onsite evaluation (ROSE) in breast cytology at the time of FNAC, and to assess the relationship between micronucleus (MN) scoring and various breast lesions in cytology. Methods: The study was conducted on 70 patients with breast lumps in the Department of Pathology in Government Medical College, Patiala, and comprised evaluation of ROSE and MN scoring in breast FNAC by the use of New Yokohama system of reporting. Results: On ROSE, 11 out of 70 patients were categorized under category I according to the Yokohama system of reporting and on the same sitting with repeat FNAC after performing the ROSE; nine cases were upgraded for cytological reporting and two remained in category I. According to as per the International Academy of Cytology (IAC) Yokohama system of reporting (2016) cases were categorized as category I – 2 (2.9%), category II – 46 (65.7%), category III – 7 (10.1%), category IV – 5 (7.1%), and category V – 10 (14.2%). In MN scoring, MN with the highest score of 14–17/1000 epithelial cells was in category V (malignant), and the lowest score was 0–1/1000 epithelial cells in category II (benign). Conclusion: ROSE is an easy, safe, and cost-effective method. IAC Yokohama system for reporting (2016) provides a comprehensive way of categorizing various breast lesions on FNAC with clinical correlation. MN score is a good biomarker in differentiating benign, atypical, and malignant breast lesions.

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&amp;lt;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&amp;lt;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.

Role of P63 in Benign and Malignant Lesions of Breast

Introduction: Breast carcinoma is leading cause of cancer death in women. Breast lesions constitute heterogeneous group of diseases with wide variety of etiologies ranging from inflammatory-benign- malignant lesions. There are several reported markers for immunohistochemical detection of myoepithelial cells. Smooth muscle specific proteins, such as smooth muscle actin, smooth muscle myosin heavy chain, calponin and h-caldesmon are used to highlight myoepithelium. p63 antibody is myoepithelial cell marker that selectively stains nuclei. It is negative in stromal, myofibroblastic and adipocytic cells.Aims and Objectives: The aim of this study was to establish role of p63 expression in distinguishing benign breast lesions, premalignant lesions and malignant tumors of breast.Materials and Methods: 30 cases were selected from core biopsy, lumpectomy and mastectomy specimens ofbreast received at department of Pathology, Chalmeda Anand Rao Institute of Medical Sciences during the period of January 2021 to December 2021 and were studied prospectively. All specimens were processed according to CAP protocol and reported . Immunohistochemistry was performed to determine p63 expression in those specimens. p63 expression was evaluated as continuous positive/discontinuous positive/negative.Ethical Approval: This study was reviewed and approved by institute ethics committee, CAIMS, Karimnagar.Results: Among total 30 cases, 18 cases (60%) were benign lesions and all were positive for p63 expression. 3 cases (9.99%) were premalignant and were least positive for p63 expression. All malignant cases 9 cases (29.99%) were negative for p63 expression.Conclusion: The Positive correlation was seen between histomorphological features and p63 scoring in all the lesions, So p63 is good Immunohistochemical marker for evaluating breast lesions.

Abstract CT273: Unique multicenter trial design to investigate ARTIDIS nanomechanical generated measurements for early breast lesions (ANGEL)

Abstract Background: The conventional diagnosis of breast cancer followed by molecular subtyping for therapy selection is a lengthy process and associated with patient and clinician anxiety. Efficient, bedside approaches are desirable to drive fast diagnosis and early planning of clinical management. This clinical trial (NCT06085833) tackles the novel concept of automated and reliable tissue diagnostics (ARTIDIS) based on the measurement of nanomechanical signature of fresh clinical biopsies from patients with breast lesions. This study is based on our previous single center clinical study (Basel NANO) where tissue nanomechanical signature can: 1) reliably distinguish benign and malignant breast lesions, 2) predict the presence of metastatic disease based on imminent aggressiveness rating and 3) predict the response to neoadjuvant chemotherapy from baseline biopsies. The current study aims to prospectively validate the efficacy of ARTIDIS system as an aid to diagnosis, assessment of breast cancer prognosis and prediction of therapy response, particularly in the context of neoadjuvant therapy (Natira). Methods: A cohort of 2,705 patients with breast lesions, who are clinically indicated for core needle biopsy (CNB) are being enrolled, from diverse ethnic and socioeconomic backgrounds. Single fresh CNB will be transferred into tissue preservation buffer and measured by ARTIDIS device within 1-3 hours to collect thousands of nanomechanical measurements. Undisrupted CNB will be fixed and returned to standard diagnostic workflow, remaining unaltered for downstream assessments. Nanomechanical measurement data are prospectively analyzed in a blind manner before the collection of histopathology and follow up clinical data. The primary endpoint of the study is to validate ARTIDIS potential in diagnosis of breast lesions (benign vs malignant), secondary endpoints address whether nanomechanical signature can differentiate subtypes of breast cancer, associate with clinical outcome and guide treatment decisions in NAT setting. Follow up data will be collected regularly up to 10 years after patient enrollment. Results: The multicenter ANGEL study is a prospective validation of the NANO (University Hospital Basel, Switzerland) - first ever performed clinical study which investigated the diagnostic, prognostic, and predictive value of tissue nanomechanical signature in patients with breast cancer. The ANGEL study takes advantage of ARTIDIS non-disruptive technology and is fully integrated into routine clinical workflow. The study started enrollment in 11/02/2023, and is expected to complete by 2025. The seamless integration of ARTIDIS within the standard clinical settings, its automatization, bedside implementation, and the lack of additional burden to patients enables effective reach of a diverse population through local hospitals and communities. Conclusion: This study presents the first of its kind as a direct prospective, multicenter- based translation of the tissue nanomechanical signature into clinical settings. This unique trial design allows the prospective development of ARTIDIS as an aid to diagnosis, prognosis and therapy optimization in patients with breast cancer. The innovative trial design of this study may also further the development of strategies to increase reach to underrepresented communities. Citation Format: Karla A. Sepulveda, Ashley Roark, Sagar Dhamne, Chandandeep Nagi, Ivan Marin, Iqbal Tabish, Sara Nizzero, Mariam Gachechiladze, Tobias Appenzeller, Philipp Oertle, Marko Loparic, Susan G. Hilsenbeck, Marija Plodinec, Alastair Thompson. Unique multicenter trial design to investigate ARTIDIS nanomechanical generated measurements for early breast lesions (ANGEL) [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 CT273.

Osseous Metaplasia of the Breast: A Series of Rare Cases

Osseous metaplasia is a reversible condition in which non-osseous soft tissue is replaced by bone. This is most commonly seen in musculoskeletal system and central nervous system. Osseous metaplasia in breast is a rare event. In this case series, we have reported 4 cases of osseous metaplasia of breast. 1 case of Osseous metaplasia in benign phyllodes tumor, 1 case of Osseous metaplasia in fibroadenoma, 1 case of Osseous metaplasia in invasive breast carcinoma and 1 extremely rare case of Osseous metaplasia of breast presenting as breast lump without any other associated pathology. Since osseous metaplasia of breast is a rare phenomenon, this entity specially in association with benign breast disease conditions pose a great challenge for accurate diagnosis.

Development and validation of a model and nomogram for breast cancer diagnosis based on quantitative analysis of serum disease-specific haptoglobin N-glycosylation

BackgroundA better diagnostic marker is in need to distinguish breast cancer from suspicious breast lesions. The abnormal glycosylation of haptoglobin has been documented to assist cancer diagnosis. This study aims to evaluate disease-specific haptoglobin (DSHp)-β N-glycosylation as a potential biomarker for breast cancer diagnosis.MethodsDSHp-β chains of 497 patients with suspicious breast lesions who underwent breast surgery were separated from serum immunoinflammatory-related protein complexes. DSHp-β N-glycosylation was quantified by mass spectrometric analysis. After missing data imputation and propensity score matching, patients were randomly assigned to the training set (n = 269) and validation set (n = 113). Logistic regression analysis was employed in model and nomogram construction. The diagnostic performance was analyzed with receiver operating characteristic and calibration curves.Results95 N-glycopeptides at glycosylation sites N207/N211, N241, and N184 were identified in 235 patients with benign breast diseases and 262 patients with breast cancer. DSHp-β N-tetrafucosyl and hexafucosyl were significantly increased in breast cancer compared with benign diseases (p < 0.001 and p = 0.001, respectively). The new diagnostic model and nomogram included GN2F2, G6N3F6, GN2FS at N184, G-N&G2S2, G2&G3NFS, G2N3F, GN3 at N207/N211, CEA, CA153, and could reliably distinguish breast cancer from benign diseases. For the training set, validation set, and training and validation sets, the area under the curves (AUCs) were 0.80 (95% CI: 0.75–0.86, specificity: 87%, sensitivity: 62%), 0.77 (95% CI:0.69–0.86, specificity: 75%, sensitivity: 69%), and 0.80 (95% CI:0.76–0.84, specificity: 77%, sensitivity: 68%), respectively. CEA, CA153, and their combination yielded AUCs of 0.62 (95% CI: 0.56–0.67, specificity: 29%, sensitivity: 90%), 0.65 (95% CI: 0.60–0.71, specificity: 74%, sensitivity: 51%), and 0.67 (95% CI: 0.62–0.73, specificity: 60%, sensitivity: 68%), respectively.ConclusionsThe combination of DSHp-β N-glycopeptides, CEA, and CA153 might be a better serologic marker to differentiate between breast cancer and benign breast diseases. The dysregulated N-glycosylation of serum DSHp-β could provide insights into breast tumorigenesis.

Study on the differential diagnosis of benign and malignant breast lesions using a deep learning model based on multimodal images.

To establish a multimodal model for distinguishing benign and malignant breast lesions. Clinical data, mammography, and MRI images (including T2WI, diffusion-weighted images (DWI), apparent diffusion coefficient (ADC), and DCE-MRI images) of 132 benign and breast cancer patients were analyzed retrospectively. The region of interest (ROI) in each image was marked and segmented using MATLAB software. The mammography, T2WI, DWI, ADC, and DCE-MRI models based on the ResNet34 network were trained. Using an integrated learning method, the five models were used as a basic model, and voting methods were used to construct a multimodal model. The dataset was divided into a training set and a prediction set. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the model were calculated. The diagnostic efficacy of each model was analyzed using a receiver operating characteristic curve (ROC) and an area under the curve (AUC). The diagnostic value was determined by the DeLong test with statistically significant differences set at P < 0.05. We evaluated the ability of the model to classify benign and malignant tumors using the test set. The AUC values of the multimodal model, mammography model, T2WI model, DWI model, ADC model and DCE-MRI model were 0.943, 0.645, 0.595, 0.905, 0.900, and 0.865, respectively. The diagnostic ability of the multimodal model was significantly higher compared with that of the mammography and T2WI models. However, compared with the DWI, ADC, and DCE-MRI models, there was no significant difference in the diagnostic ability of these models. Our deep learning model based on multimodal image training has practical value for the diagnosis of benign and malignant breast lesions.

A Study Comparing Centchroman and Evening Primrose Oil in the Treatment of Benign Breast Disease

ABSTRACT Introduction: Females seeking medical attention at breast clinics commonly present with nonmalignant breast conditions, including nonspecific breast pain or distinct masses like fibroadenomas. Due to its variability, it may be difficult to quantify breast pain. The purpose of the research was to compare centchroman and evening primrose oil to identify a cost-effective, secure, and efficient treatment for benign breast disease. Material and Methods: In this prospective hospital-based observational study, 100 breast diseases with or without lumpiness for 1 year were included and divided into two groups with 50 cases each, Group-A (Centchroman) and Group-B (Evening primrose oil). Results: Centchroman exhibited a significantly greater treatment response for alleviating pain-free mastalgia compared to evening primrose oil. Additionally, centchroman showed an excellent response (P &lt; .05). Among participants with mastalgia, centchroman significantly reduced the number of mastalgia patients with tender nodularity post-treatment (P = .035) than evening primrose oil. On the basis of fibroadenoma, partial and complete response was significantly seen in higher number of cases in the centchroman group (P = .007). Conclusion: Centchroman therapy demonstrates that the treatment for benign breast disease is safe, effective, and economical.

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.

Machine learning and new insights for breast cancer diagnosis.

Breast cancer (BC) is the most prominent form of cancer among females all over the world. The current methods of BC detection include X-ray mammography, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and breast thermographic techniques. More recently, machine learning (ML) tools have been increasingly employed in diagnostic medicine for its high efficiency in detection and intervention. The subsequent imaging features and mathematical analyses can then be used to generate ML models, which stratify, differentiate and detect benign and malignant breast lesions. Given its marked advantages, radiomics is a frequently used tool in recent research and clinics. Artificial neural networks and deep learning (DL) are novel forms of ML that evaluate data using computer simulation of the human brain. DL directly processes unstructured information, such as images, sounds and language, and performs precise clinical image stratification, medical record analyses and tumour diagnosis. Herein, this review thoroughly summarizes prior investigations on the application of medical images for the detection and intervention of BC using radiomics, namely DL and ML. The aim was to provide guidance to scientists regarding the use of artificial intelligence and ML in research and the clinic.

Оцінка впливу гінекологічної патології на шанси живонародження серед жінок із повторними невдачами імплантації

Aim - to study the prognostic impact of the presence of gynecological pathology on live birth in women with multiple negative implantation attempts in the context of the proposed methods of examination and treatment, such as preimplantation genetic diagnosis of embryos and individualization of the endometrial preparation protocol, taking into account the results of the assessment of the implantation window. Materials and methods. The prospective cohort study included 93 women with infertility treated by in vitro fertilization (IVF). Patients had repeated failed implantation attempts and were divided into three groups: the Group 1 - patients who were treated with genetically untested embryos according to a standard fixed stimulation protocol, the Group 2 - patients who were treated with euploid embryos after preimplantation genetic screening according to a standard fixed protocol; the Group 3 - patients treated with euploid embryos after preimplantation genetic screening and determination of the implantation window with subsequent modification of the stimulation protocol, according to the results of the endometrial examination. The implantation window was determined by three-time aspiration biopsy of the endometrium during the luteal phase of the menstrual cycle. The samples were analyzed by scanning electron microscopy. Based on the results, the endometrial preparation protocol was individualized for the next IVF attempt. Preimplantation diagnostics of embryos was performed using the next generation method. Statistical analysis was performed using IBM SPSS V25.0 for Windows software. Results. According to the results obtained, the presence of genital pathology reduced the chance of live birth by 30% in patients with repeated failed implantation attempts. Pathologies such as endometriosis, including endometrioid ovarian cysts, benign breast disease and Asherman syndrome have a negative effect on the chance of live birth among patients who have undergone infertility treatment with IVF. Conclusions. The presence of gynecologic pathology reduces the chances of live birth in patients with repeated failed implantation attempts undergoing IVF treatment. The study was conducted in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee for all participants. Informed consent was obtained from the patients. No conflict of interests was declared by the authors.

Порушення менструального циклу в жінок репродуктивного віку: сучасний погляд на проблему (огляд літератури)

Menstrual health, as a component of reproductive health - a state of complete physical, mental and social well-being, and not just the absence of diseases, is an integral part of improving the health of women around the world, achieving the goals of sustainable development of society and realizing gender equality and human rights. Aim of the study is to analyze data on the problem of menstrual cycle disorders in women of reproductive age, modern classifications of menstrual cycle disorders, and also to propose an option for correcting these disorders. Preserving menstrual health is inextricably linked to the possibility of access to appropriate medical services and resources, including timely diagnosis of menstrual cycle disorders, their treatment and prevention. The article presents modern data on the nomenclature, definition of the norm and pathology of the menstrual cycle, classification systems of its violations. The expediency and application of the complex herbal preparation Normomens® is a highly effective alternative therapy for menstrual cycle disorders, PMS symptoms, dysmenorrhea, fibrocystic disease of the mammary glands, infertility and hyperproliferative processes of the pelvic organs in women of reproductive age. No conflict of interests was declared by the authors.

Using the DNA Integrity Number to Analyze DNA Quality in Specimens Collected from Liquid-Based Cytology after Fine-Needle Aspiration of Breast Tumors and Lesions

Introduction: Cancer genome analysis using next-generation sequencing requires adequate and high-quality DNA samples. Genomic analyses were conventionally performed using formalin-fixed paraffin-embedded sections rather than cytology samples such as cell block or smear specimens. Specimens collected from liquid-based cytology (LBC) have the potential to be sources of high-quality DNA suitable for genetic analysis even after long-term storage. Methods: We collected breast tumor/lesion fractions from 92 residual LBC specimens using fine-needle aspiration (FNA) biopsy, including breast carcinoma (1 invasive carcinoma and 4 ductal carcinomas in situ), papillomatous lesion (5 intraductal papillomas), and fibroepithelial lesion (19 phyllodes tumors and 53 fibroadenomas) samples, and others (1 ductal adenoma, 1 hamartoma, 1 fibrocystic disease, and 7 unknown). DNA was extracted from all samples and subjected to DNA integrity number (DIN) score analysis. Results: Average DIN score collected from 92 LBC specimens was significantly higher score. In addition, high-quality DNA with high DIN values (7.39 ± 0.80) was successfully extracted more than 12 months after storage of residual LBC specimens. Conclusion: Residual LBC specimens collected from FNA of the breast were verified to carry high-quality DNA and could serve as an alternate source for genetic analysis.

Fibrocystic changes of the mammary glands: interpretation of the diagnosis, issues of diagnosis and treatment (Literature review)

Fibrocystic changes of the mammary glands: interpretation of the diagnosis, issues of diagnosis and treatment (Literature review)