Detección de la infiltración de la cadena mamaria interna en pacientes con cáncer de mama mediante PET/RM con 18F-FDG y sus implicaciones terapéuticas / Detection of internal mammary chain infiltration in breast cancer patients by [18F]FDG PET/MRI: Therapy implications

Objetivo: Evaluar la tasa de detección y la implicación terapéutica de la infiltración de la cadena mamaria interna (ICMI) mediante tomografía por emisión de positrones (PET) y resonancia magnética (RM) con 18F-fluorodesoxiglucosa (18F-PET/RM) en la estadificación de pacientes con cáncer de mama. Método: Estudio prospectivo, 41 mujeres con cáncer de mama (estadio ≥ IIB) estadificadas mediante 18F-FDG-PET/RM. Estudio en dos fases: imágenes mamarias (decúbito prono), cuerpo completo (supino). Estadificación TNM por consenso entre especialista en Medicina Nuclear y Radiología. Estudio vaso aferente (VA) a cadena mamaria interna (CMI) por RM mamaria. Correlación ICMI con edad, VA-CMI, estadificación T, cuadrante, infiltración axilar y a distancia. Revaloración terapéutica en comité multidisciplinar. Resultados: Tasa de detección de ICMN de 34% (14/41), siendo 8/14 < 55 años. Todas las 14 pacientes con ICMI muestran VA-CMI, en seis de ellas (43,9%) sin VA-axilar. De 27/41 sin ICMI, en 13 (48,1%) solo VA-axilar, en los 14 restantes (51,9%) VA-axilar y VA-CMI. Un total de 57% (8/14) son multicéntricos y 42% (6/14) focales, en cuadrantes internos en 4/6 (66,7%). En 1/14 (7,1%) solo ICMI, en 9/14 (64,3%) axilar y CMI y en 4/14 (28,6%) lesiones a distancia. Decisión del comité: sin tratamiento adicional en 27/41 (65,8%), radioterapia torácica en 10/41 (24,4%) y terapia sistémica en 4/41 (9,7%). Conclusión: La tasa de detección de la ICMI en la estadificación del cáncer de mama mediante 18F-FDG PET/RM es de 34%. Son factores asociados la edad, los tumores multicéntricos, los de cuadrantes internos, la existencia de VA-CMI, la estadificación NM. La evidencia de ICMI permite la individualización de la terapia, indicando la radioterapia torácica en 24,4%.(AU)

Objective: To evaluate the detection rate and therapeutic implication of the infiltration of the internal mammary chain (IMCI) by [18F]FDG PET/MRI for staging of patients with breast cancer. Methods: Prospective study including 41 women with breast cancer (stage ≥IIB) staged by [18F]FDG PET/MR. Two-phase exam: breast imaging (prone), whole-body (supine). TNM stage assessed by peer consensus with Nuclear Medicine and Radiology specialists. Study of the afferent vessel (AV) to IMC by breast MRI. IMCI was correlated with age, AV-IMC, T stage, breast quadrants, axillary and distant infiltration. Therapeutic re-evaluation by a multidisciplinary committee. Results: IMCI detection rate of 34% (14/41), with 8/14 patients under 55 years of age. All 14 patients with IMCI showed AV-IMC, 6 of them (43.9%) without VA-axillary. Of 27/41 patients without IMCI, in 13 (48.1%) only AV-axillary was found, in the remaining 14 (51.9%), AV-axillary and AV-IMC was found. In 57% (8/14) tumours were multicentric and 42% (6/14) focal, in inner quadrants in 4/6 (66.7%). In 1/14 patient (7.1%) only IMCI was found, in 9/14 (64.3%) axillary and IMC, in 4/14 patients (28.6%) distant lesions were detected. Committee re-evaluation: no further treatment in 27/41 patients (65.8%), thoracic radiotherapy in 10/41 patients (24.4%), systemic therapy in 4/41 patients (9.7%). Conclusion: Our detection rate of IMCI in breast cancer staging by [18F]FDG PET/MR was 34%. Related factors were age, multicentric tumours, inner quadrants, detection of AV-IMC, NM staging.The evidence of IMCI allowed tailored therapy, with thoracic radiotherapy implementation in 24.4% of patients.(AU)

Concordancia entre SPECT portátil y la gammagrafía convencional para detección de ganglio centinela en cáncer de mama / Concordance between freehand SPECT and conventional scintigraphy for sentinel lymph node detection in breast cancer

Introducción: La SPECT portátil puede ser una técnica de imagen útil para la planificación preoperatoria de la biopsia selectiva del ganglio centinela (BSGC) ya que permite la localización del ganglio centinela (GC) mediante imágenes tomográficas en 3D y en tiempo real y determina su profundidad, después de unos minutos de exploración. El objetivo del estudio fue evaluar la correlación entre el número de GC detectados entre las imágenes de la SPECT portátil y la linfogammagrafía (LG). Materiales y métodos: Cien pacientes con diagnóstico de cáncer de mama infiltrante y sin evidencia clínica de afectación ganglionar, se sometieron prospectivamente a una BSGC. El estudio preoperatorio incluyó imágenes de SPECT portátil a los 15 min tras la inyección y de LG a los 25 y 60-90 min (precoz y tardía). Se analizó el acuerdo observado y se realizó un estudio de concordancia entre el número de GC detectados con SPECT portátil y LG. Resultados: El acuerdo observado en la detección de GC entre SPECT portátil y LG precoz fue del 72%; entre SPECT portátil y LG tardía del 85%, y entre la LG precoz y la tardía de un 87%. En el estudio de concordancia se registró una concordancia moderada entre la SPECT portátil y la LG precoz (coeficiente kappa: 0,42); una concordancia moderada-alta entre la SPECT portátil y la LG tardía (coeficiente kappa: 0,60), y una concordancia de moderada-alta entre la LG precoz y la tardía (coeficiente kappa: 0,70), sin diferencias significativas entre ellos (valor p=0,16). Conclusión: La SPECT portátil presentó una concordancia moderada-alta con los estudios de imagen convencional y podría ser una alternativa válida para el estudio prequirúrgico de la BSGC en el cáncer de mama.(AU)

Introduction: Freehand SPECT can be a useful imaging technique for preoperative planning of sentinel lymph node biopsy (SLNB) as it allows localization of the sentinel node by 3D and real-time tomographic imaging and determines its depth after a few minutes of scanning. The aim of the study was to evaluate the correlation between the number of detected SNs between freehand SPECT images and lymphoscintigraphy (LS). Materials and methods: One hundred patients with a diagnosis of invasive breast cancer and no clinical evidence of lymph node involvement prospectively underwent SLNB. The preoperative study included freehand SPECT imaging at 15min after injection and LS imaging at 25 and 60–90min after injection (early and late). The observed agreement was analyzed and a concordance study was performed between the number of SNs detected with freehand SPECT and LS. Results: The observed agreement in the detection of SNs between freehand SPECT and early LS was 72%; between freehand SPECT and late LS was 85%; and between early and late LS was 87%. In the concordance study, there was moderate concordance between freehand SPECT and early LS (kappa coefficient: 0.42); moderate-high concordance between freehand SPECT and late LS (kappa coefficient: 0.60); and moderate-high concordance between early and late LS (kappa coefficient: 0.70), with no significant differences between them (p-value=0.16). Conclusion: Freehand SPECT showed a moderate-high concordance with conventional imaging studies and could be a valid alternative for the presurgical study of SLNB in breast cancer.(AU)

Equipo multidisciplinar de cirugía radioguiada: Alternativa de cambio al paradigma actual / Multidisciplinary radio-guided surgery team: Alternative to change the current paradigm

IntroducciónAnte el aumento constante de la demanda asistencial de exploraciones relacionadas con cirugía radioguiada (CRG), nuestro hospital adoptó incluir en el equipo de CRG nuevos perfiles profesionales con el fin de reducir parcialmente el tiempo de dedicación de los médicos nucleares a esta tarea.Objetivos: Analizar el proceso de incorporación de los perfiles de Técnico Superior en Imagen para el Diagnóstico (TSID) y Enfermera Referente de Ganglio Centinela (ERGC), evaluando su despliegue en los procedimientos ligados a la técnica. Material y métodos: Análisis de la actividad de CRG durante el periodo 2018-2022, centrándolo en los procedimientos prequirúrgicos y quirúrgicos relativos a cáncer de mama (CaM) y melanoma maligno (MM), por ser aquellas patologías en las que se concentró la transferencia de competencias asistenciales. Evolución cronológica de las competencias asumidas por los diferentes perfiles durante su integración en el equipo de CRG. Resultados: La actividad asistencial de CRG durante el periodo analizado experimentó un incremento del 109%. CaM y MM son las patologías que aglutinaron con diferencia una mayor demanda asistencial. La transferencia de competencias en estas dos patologías se ha producido de manera progresiva, asumiendo en 2022 el 74% (460/622) de la fase de administración el ERGC y el 64% (333/519) de las cirugías el TSID. Conclusiones: La creación de un equipo multidisciplinar de CRG, que incluye distintos perfiles profesionales (MN, ERGC y TSID), es una eficaz estrategia para dar respuesta al incremento de la complejidad y número de todos los procedimientos relacionados con la CRG.(AU)

Introduction: Given the constant increase in the healthcare demand for examinations related to radio-guided surgery (RGS), our hospital adopted new professional profiles in the RGS team, in order to partially reduce the time spent by nuclear medicine physicians on this task. Aim: To analyze the process of incorporating the profiles of Superior Diagnostic Imaging Technician (TSID) and Sentinel Node Referent Nurse (ERGC), evaluating their deployment in the procedures linked to the technique. Material and methods: Analysis of RGS activity during the period 2018-2022, focusing on pre-surgical and surgical procedures related to breast cancer (BC) and malignant melanoma (MM), as they are those pathologies on which the transfer of care competencies was concentrated. Chronological evolution of the competencies assumed by the different profiles during their integration into the RGS team. Results: RGS's healthcare activity during the analyzed period experienced an increase of 109%. BC and MM were the pathologies that accounted for by far the greatest demand for care. The transfer of competencies in these two pathologies occurred in a progressive and staggered manner, with 74% (460/622) of the administration phase being carried out by the ERGC and 64% (333/519) of the surgeries by the TSID in 2022. Conclusions: The creation of a multidisciplinary RGS team that includes different professional profiles (NM, ERGC and TSID) is an effective strategy to respond to the increase in the complexity and number of all procedures related to RGS.(AU)

Zinc-Iron Bimetallic Peroxides Modulate the Tumor Stromal Microenvironment and Enhance Cell Immunogenicity for Enhanced Breast Cancer Immunotherapy Therapy.

Immunotherapy has emerged as a potential approach for breast cancer treatment. However, the rigid stromal microenvironment and low immunogenicity of breast tumors strongly reduce sensitivity to immunotherapy. To sensitize patients to breast cancer immunotherapy, hyaluronic acid-modified zinc peroxide-iron nanocomposites (Fe-ZnO2@HA, abbreviated FZOH) were synthesized to remodel the stromal microenvironment and increase tumor immunogenicity. The constructed FZOH spontaneously generated highly oxidative hydroxyl radicals (·OH) that degrade hyaluronic acid (HA) in the tumor extracellular matrix (ECM), thereby reshaping the tumor stromal microenvironment and enhancing blood perfusion, drug penetration, and immune cell infiltration. Furthermore, FZOH not only triggers pyroptosis through the activation of the caspase-1/GSDMD-dependent pathway but also induces ferroptosis through various mechanisms, including increasing the levels of Fe2+ in the intracellular iron pool, downregulating the expression of FPN1 to inhibit iron efflux, and activating the p53 signaling pathway to cause the failure of the SLC7A11-GSH-GPX4 signaling axis. Upon treatment with FZOH, 4T1 cancer cells undergo both ferroptosis and pyroptosis, exhibiting a strong immunogenic response. The remodeling of the tumor stromal microenvironment and the immunogenic response of the cells induced by FZOH collectively compensate for the limitations of cancer immunotherapy and significantly enhance the antitumor immune response to the immune checkpoint inhibitor αPD-1. This study proposes a perspective for enhancing immune therapy for breast cancer.

Therapeutic effects of compression therapy on taxane-induced peripheral neuropathy incidence, negative emotions, and sleep disorders in patients with breast cancer.

PURPOSE: To explore the effects of compression therapy on chemotherapy-induced peripheral neuropathy (CIPN), anxiety, depression, and sleep disorders in breast cancer patients administered taxanes. METHODS: Eighty patients with breast cancer undergoing chemotherapy at Tangshan People's Hospital between October 2022 and July 2023 were randomly divided into control (n = 40) and intervention (n = 40) groups. The control group received routine care, while intervention group received compression therapy in addition to routine care (30 min before the infusion of chemotherapy drugs, patients wore surgical gloves on their hands that were one size smaller than the appropriate size and elastic socks on their feet until 30 min after the infusion). The incidence of CIPN, anxiety, depression, and sleep scores, were compared between these groups before and after compression therapy during chemotherapy cycles 2, 4, and 6. RESULTS: The general characteristics did not differ significantly between the groups (P > 0.05). The CIPN incidence, anxiety and depression scores, and sleep scores also did not differ significantly between the two groups before and after the intervention period (P > 0.05). After the fourth and sixth cycles of intervention, the incidence of CIPN (≥ 1 and ≥ 2), anxiety and depression scores, and sleep scores were significantly lower in the intervention group than in the control group (P < 0.05). CONCLUSION: Compression therapy can effectively reduce the incidence of CIPN, as well as improve the level of anxiety, depression, and sleep disorders in chemotherapy patients. Therefore, medical personnel should closely observe the physical and psychological changes in patients undergoing chemotherapy and provide corresponding preventive measures. REGISTRATION NUMBER: RMYY-LLKS-2022-054. DATE OF REGISTRATION: September 25, 2022.

Iron Oxide Nanoparticles Inhibit Tumor Progression and Suppress Lung Metastases in Mouse Models of Breast Cancer.

Systemic exposure to starch-coated iron oxide nanoparticles (IONPs) can stimulate antitumor T cell responses, even when little IONP is retained within the tumor. Here, we demonstrate in mouse models of metastatic breast cancer that IONPs can alter the host immune landscape, leading to systemic immune-mediated disease suppression. We report that a single intravenous injection of IONPs can inhibit primary tumor growth, suppress metastases, and extend survival. Gene expression analysis revealed the activation of Toll-like receptor (TLR) pathways involving signaling via Toll/Interleukin-1 receptor domain-containing adaptor-inducing IFN-ß (TRIF), a TLR pathway adaptor protein. Requisite participation of TRIF in suppressing tumor progression was demonstrated with histopathologic evidence of upregulated IFN-regulatory factor 3 (IRF3), a downstream protein, and confirmed in a TRIF knockout syngeneic mouse model of metastatic breast cancer. Neither starch-coated polystyrene nanoparticles lacking iron, nor iron-containing dextran-coated parenteral iron replacement agent, induced significant antitumor effects, suggesting a dependence on the type of IONP formulation. Analysis of multiple independent clinical databases supports a hypothesis that upregulation of TLR3 and IRF3 correlates with increased overall survival among breast cancer patients. Taken together, these data support a compelling rationale to re-examine IONP formulations as harboring anticancer immune (nano)adjuvant properties to generate a therapeutic benefit without requiring uptake by cancer cells.

Adherence to adjuvant endocrine therapy for breast cancer: a qualitative exploration of attribution of symptoms among post-menopausal women.

PURPOSE: Oral adjuvant endocrine therapy (AET) is an effective treatment for hormone receptor positive breast cancer to decrease recurrence and mortality, but adherence is poor. This study explored post-menopausal women's experiences with AET, with a particular focus on adherence to AET as well as distress and symptoms experienced prior to and during AET treatment. METHODS: Participants were recruited from a hospital registry, stratified by adherence to/discontinuation of AET. Telephone interviews followed a semi-structured interview guide and were recorded and transcribed verbatim. Transcripts were systematically coded using team-based coding, with analysis of themes using a grounded theory approach. RESULTS: Thirty-three participants were interviewed; ages ranged from 57 to 86 years. Participants included 10 discontinued patients and 23 patients who completed their AET course or were adherent to AET at the time of interviewing. Both adherent and discontinued patients reported symptoms throughout their AET treatment course, and both attributed symptoms to factors other than AET (e.g., older age and pre-existing comorbidities). However, discontinued patients were more likely to attribute symptoms to AET and to describe difficulty managing their symptoms, with some directly citing symptoms as the reason for discontinuing AET therapy. Conversely, adherent patients were more likely to describe the necessity of taking AET, despite symptoms. CONCLUSIONS: AET adherence was associated with beliefs about AET, symptom attribution, and symptom management. Routine symptom monitoring during AET and addressing both symptoms and patients' understanding of their symptoms may promote adherence to AET.

Juvenile Papillomatosis of the Breast: a Report of Two Cases with Review of the literature.

Background: Juvenile papillomatosis (JP) of the breast is a rare and benign proliferative disorder affecting young women. The affected patients tend to have an increased risk of breast cancer development during follow-up. Objective: This article aims to highlight a rare entity of breast disease, that harbor risk of breast cancer. Case Presentation: Here, we present 2 cases of JP in young females; the first case is a 13 year-old presented with spontaneous nipple discharge, while the other patient is a 24 year-old presented with a right breast lump. Both patients had a total excision of the breast lesions, revealing JP at histology. Discussion: Juvenile Papillomatosis is considered a clinicopathological entity and is usually misdiagnosed as fibroadenoma clinically and radiologically, which requires histological correlation. The histologic findings are well-defined (hyperplasia, papillomatosis, and multiple cysts with foamy histiocytes).The controversy in management between surgery and observation is because of insufficient knowledge about the direct relationship between JP and subsequent cancer. Conclusion: Considering the risk of developing breast cancer in JP, enrolling patients and their families in a close follow-up and surveillance program is crucial.

Strong Protection by 4-Hydroxyestrone against Erastin-Induced Ferroptotic Cell Death in Estrogen Receptor-Negative Human Breast Cancer Cells: Evidence for Protein Disulfide Isomerase as a Mechanistic Target for Protection.

Ferroptosis is a recently identified form of regulated cell death, characterized by excessive iron-dependent lipid peroxidation. Recent studies have demonstrated that protein disulfide isomerase (PDI) is an important mediator of chemically induced ferroptosis and also a new target for protection against ferroptosis-associated cell death. In the present study, we identified that 4-hydroxyestrone (4-OH-E1), a metabolic derivative of endogenous estrogen, is a potent small-molecule inhibitor of PDI, and can strongly protect against chemically induced ferroptotic cell death in the estrogen receptor-negative MDA-MB-231 human breast cancer cells. Pull-down and CETSA assays demonstrated that 4-OH-E1 can directly bind to PDI both in vitro and in intact cells. Computational modeling analysis revealed that 4-OH-E1 forms two hydrogen bonds with PDI His256, which is essential for its binding interaction and thus inhibition of PDI's catalytic activity. Additionally, PDI knockdown attenuates the protective effect of 4-OH-E1 as well as cystamine (a known PDI inhibitor) against chemically induced ferroptosis in human breast cancer cells. Importantly, inhibition of PDI by 4-OH-E1 and cystamine or PDI knockdown by siRNAs each markedly reduces iNOS activity and NO accumulation, which has recently been demonstrated to play an important role in erastin-induced ferroptosis. In conclusion, this study demonstrates that 4-OH-E1 is a novel inhibitor of PDI and can strongly inhibit ferroptosis in human breast cancer cells in an estrogen receptor-independent manner. The mechanistic understanding gained from the present study may also aid in understanding the estrogen receptor-independent cytoprotective actions of endogenous estrogen metabolites in many noncancer cell types.

Assessment of breast cancer awareness among female pharmacy students at a university in Turkey.

BACKGROUND: Female breast cancer is the most frequently diagnosed cancer, and knowledge of breast cancer risk factors, and symptoms is crucial for early diagnosis and prevention. This study aims to evaluate breast cancer awareness among female students at a pharmacy faculty in Turkey. METHODS: A cross-sectional online survey study was conducted among female students at the Suleyman Demirel University Faculty of Pharmacy between 2 November and 17 November 2023, in Isparta, Turkey. RESULTS: This survey was answered by 237 (74.5%) female students. The median breast cancer risk factors score was 8 (IQR, 5-11), and the median breast cancer symptoms score was 5 (IQR, 2-8). Additionally, the breast cancer risk factors score was 46.16% (mean/max = 8.31/18, SD = 4.33) and the breast cancer symptom score was 58.5% (mean/max = 4.68/8, SD = 2.8). Few of the respondents (26.2%, and 20.3%, respectively) knew breast cancer risk factors such as late menopause, and no childbirth experience. Most respondents correctly answered symptoms of breast cancer, such as a painless and palpable breast lump, indrawing of the nipple, and sudden changes in breast shape (76.8%,44.3%, and 67.1% respectively). The students' sources of information were medical websites (29.5%), social media (27%), physicians (22.8%), friends & family (14.8%), and pharmacists (5.9%). CONCLUSIONS: This study showed that students' knowledge of breast cancer risk factors was poor, but their knowledge of breast cancer symptoms was acceptable. Breast cancer awareness courses should be included in faculties. Additionally, more attention should be given to different educational interventions such as social media, television, and brochure distribution.

Cellular plasticity in the breast cancer ecosystem.

The complex interplay between genetically diverse tumor cells and their microenvironment significantly influences cancer progression and therapeutic responses. This review highlights recent findings on cellular plasticity and heterogeneity within the breast cancer ecosystem, focusing on the roles of cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). We discuss evidence suggesting that breast cancer cells exhibit phenotypic plasticity driven by both intrinsic genetic factors and external microenvironmental cues, impacting treatment responses and disease recurrence. Moreover, single-cell RNA sequencing studies reveal diverse subtypes of CAFs and TAMs, each with distinct functional gene expression programs and spatial organization within the tumor microenvironment. Understanding the hierarchical relationships and niche cues governing cellular phenotypes offers new opportunities for targeted therapeutic interventions. By elucidating the organizational principles of the tumor ecosystem, future therapies may target phenotypic states or entire cellular niches, advancing precision medicine approaches in breast cancer treatment.

New hopes for the breast cancer treatment: perspectives on the oncolytic virus therapy.

Oncolytic virus (OV) therapy has emerged as a promising frontier in cancer treatment, especially for solid tumours. While immunotherapies like immune checkpoint inhibitors and CAR-T cells have demonstrated impressive results, their limitations in inducing complete tumour regression have spurred researchers to explore new approaches targeting tumours resistant to current immunotherapies. OVs, both natural and genetically engineered, selectively replicate within cancer cells, inducing their lysis while sparing normal tissues. Recent advancements in clinical research and genetic engineering have enabled the development of targeted viruses that modify the tumour microenvironment, triggering anti-tumour immune responses and exhibiting synergistic effects with other cancer therapies. Several OVs have been studied for breast cancer treatment, including adenovirus, protoparvovirus, vaccinia virus, reovirus, and herpes simplex virus type I (HSV-1). These viruses have been modified or engineered to enhance their tumour-selective replication, reduce toxicity, and improve oncolytic properties.Newer generations of OVs, such as Oncoviron and Delta-24-RGD adenovirus, exhibit heightened replication selectivity and enhanced anticancer effects, particularly in breast cancer models. Clinical trials have explored the efficacy and safety of various OVs in treating different cancers, including melanoma, nasopharyngeal carcinoma, head and neck cancer, and gynecologic malignancies. Notably, Talimogene laherparepvec (T-VEC) and Oncorine have. been approved for advanced melanoma and nasopharyngeal carcinoma, respectively. However, adverse effects have been reported in some cases, including flu-like symptoms and rare instances of severe complications such as fistula formation. Although no OV has been approved specifically for breast cancer treatment, ongoing preclinical clinical trials focus on four groups of viruses. While mild adverse effects like low-grade fever and nausea have been observed, the effectiveness of OV monotherapy in breast cancer remains insufficient. Combination strategies integrating OVs with chemotherapy, radiotherapy, or immunotherapy, show promise in improving therapeutic outcomes. Oncolytic virus therapy holds substantial potential in breast cancer treatment, demonstrating safety in trials. Multi-approach strategies combining OVs with conventional therapies exhibit more promising therapeutic effects than monotherapy, signalling a hopeful future for OV-based breast cancer treatments.

Identification of miR-125a and miR-106b signature as a potential diagnostic biomarker in breast cancer tissues.

MicroRNAs (miRNAs) have essential roles in the etiology of breast cancer and are regarded as possible markers in this malignancy. In order to find new markers for breast cancer, the current study has measured expression level of four miRNAs, namely miR-125a, miR-106b, miR-96 and miR-92a-3p in the paired breast samples. Expression levels of miR-125a and miR-106b were higher in tumoral tissues compared with control tissues (Expression ratios (95% CI) = 4.01 (1.96-8.19) and 3.9 (1.95-7.81); P values = 0.0005 and 0.0003, respectively). miR-106b and miR-125a differentiated between malignant and non-malignant tissues with AUC values of 0.7 and 0.67, respectively. We detected association between expression of miR-106b and clinical stage (P = 0.03), in a way that its expression was the lowest in the advanced stages. Finally, significant relationships were found between miR-96 and miR-125a in both tumoral and non-tumoral specimens (ρ = 0.76 and 0.69, respectively). This nonparametric measure of rank correlation also showed relationship between miR-106b and miR-96 in both sets of samples (ρ = 0.63 and 0.61, respectively). Cumulatively, the assessed miRNAs, particularly miR-125a and miR-106b are putative targets for further expression and functional assays in breast cancer.

The role of transcription factor FOXA1/C2/M1/O3/P1/Q1 in breast cancer.

Breast cancer is a common malignancy with the highest mortality rate among women worldwide. Its incidence is on the rise year after year, accounting for more than one-tenth of new cancers worldwide. Increasing evidence suggests that forkhead box (FOX) transcription factors play an important role in the occurrence and development of breast cancer. However, little is known about the relationship between the expression, prognostic value, function, and immune infiltration of FOX transcription factors in tumor microenvironment. We used bioinformatics to investigate expression and function of FOX factor in breast cancer. Our results revealed the expression levels of FOXA1 and FOXM1 were significantly higher in breast cancer tissues than in normal tissues. The high expression of mRNA in FOXA1 (P < .05), FOXM1 (P < .01), and FOXP1 (P < .05) groups was related to tumor stage. Survival analysis results showed that increased FOXP1 mRNA levels were significantly associated with overall survival (OS), recurrence-free survival (RFS), and distant metastasis-free survival (DMFS) in all patients with breast cancer (P < .05). Patients with the FOXA1 high-expression group had better RFS and DMFS than the low-expression group (P < .05), while patients with FOXM1 high-expression group had worse RFS, OS, and DMFS than the low-expression group (P < .05). Meanwhile, mutation analysis showed that genetic alterations in FOX transcription factors were significantly associated with shorter OS and progression-free survival (P < .05), but not with disease-free survival (P = .710) in patients with breast cancer. FOXP1, FOXA1, and FOXM1 may be used as potential biomarkers to predict the prognosis of patients with breast cancer. Functional enrichment indicated that FOX was mainly involved in cell division, cell senescence, cell cycle, and prolactin signaling pathway. In patients with breast cancer, FOXC2 expression was negatively correlated with the infiltration of B cells and positively correlated with the infiltration of neutrophils and dendritic cells. However, FOXM1 was negatively correlated with the infiltration of CD8 + T cells and macrophages and positively correlated with the infiltration of neutrophils and dendritic cells. These findings provided novel insights into the screening of prognostic biomarkers of the FOX family in breast cancer and laid a foundation for further research on the immune infiltration of the FOX transcription factor family members in tumors.

BREAST CANCER-MODULATED OMENTIN AND VASPIN PLASMA LEVELS.

Omentin and vaspin levels have been shown to change in many inflammatory diseases, the present study aimed to evaluate the omentin and vaspin levels in breast cancer patients. To do so serum samples were collected and analysed for omentin, vaspin, renal and liver function tests. The levels of creatinine (p<0.01) and urea (p<0.05) showed substantial increases, while omentin and Vaspin levels notably decreased (p<0.05). Additionally, breast cancer patients exhibited significantly higher levels of aspartate aminotransferase (AST), alkaline phosphatase (ALP), and alanine transaminase (ALT) compared to the control group (p<0.05). In comparison to the control group, individuals with breast cancer demonstrated reduced blood concentrations of omentin and vaspin and elevated levels of creatinine and urea. Additionally, liver function testing indicated lower levels of Alanine transaminase (ALT), Alkaline phosphatase (ALP), and Aspartate aminotransferase (AST) in breast cancer patients. Breast cancer patients had lower levels of omentin and vaspin, and higher levels of creatinine and urea compared to the control group. Liver function tests also indicated lower levels of AST, ALP, and ALT in breast cancer patients compared to the control group.

PARP14 Contributes to the Development of the Tumor-Associated Macrophage Phenotype.

Cancers reprogram macrophages (MΦs) to a tumor-growth-promoting TAM (tumor-associated MΦ) phenotype that is similar to the anti-inflammatory M2 phenotype. Poly(ADP-ribose) polymerase (PARP) enzymes regulate various aspects of MΦ biology, but their role in the development of TAM phenotype has not yet been investigated. Here, we show that the multispectral PARP inhibitor (PARPi) PJ34 and the PARP14 specific inhibitor MCD113 suppress the expression of M2 marker genes in IL-4-polarized primary murine MΦs, in THP-1 monocytic human MΦs, and in primary human monocyte-derived MΦs. MΦs isolated from PARP14 knockout mice showed a limited ability to differentiate to M2 cells. In a murine model of TAM polarization (4T1 breast carcinoma cell supernatant transfer to primary MΦs) and in a human TAM model (spheroids formed from JIMT-1 breast carcinoma cells and THP-1-MΦs), both PARPis and the PARP14 KO phenotype caused weaker TAM polarization. Increased JIMT-1 cell apoptosis in co-culture spheroids treated with PARPis suggested reduced functional TAM reprogramming. Protein profiling arrays identified lipocalin-2, macrophage migration inhibitory factor, and plasminogen activator inhibitor-1 as potential (ADP-ribosyl)ation-dependent mediators of TAM differentiation. Our data suggest that PARP14 inhibition might be a viable anticancer strategy with a potential to boost anticancer immune responses by reprogramming TAMs.

Navigating Breast Cancer Innovation in Uganda: Within and Without the Textbook.

The Center for Bioengineering Innovation and Design (CBID) at Johns Hopkins University (JHU) has established a comprehensive approach to addressing global health challenges. Central to CBID's modality on global health is a strategy that integrates education, research, and collaboration. Through its graduate program, CBID trains the next generation of health care innovators to address the specific needs of low- and middle-income countries (LMICs). Graduate student teams at CBID begin their year with a focus on a health care thematic area associated with a target country.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

BRCA2 Polymorphisms and Breast Cancer Susceptibility: a Multi-Tools Bioinformatics Approach.

BACKGROUND/AIMS: The main focus of this investigation is to identify deleterious single nucleotide polymorphisms (SNPs) located in the BRCA2 gene through in silico approach, thereby,providing an understanding of potential consequences regarding the susceptibility to breast cancer. METHODS: The GenomAD database was used to identify SNPs. To determine the potential adverse consequences, our study employed various prediction tools, including SIFT, PolyPhen, PredictSNP, SNAP2, PhD-SNP, and ClinVar. The pathogenicity associated with the deleterious snSNPs was evaluated bu MutPred and Fathmm. Additionally, I-Mutant and MuPro were used to assess the stability, followed by conservation and protein-protein interaction analysis using robust computational tools. The 3D structure of BRCA2 protein was generated by SwissModel, followed by validation using PROCHECK and Errat. RESULTS: The GenomAD database was used to identify a total of 7, 921 SNPs, including 1940 missense SNPs. A set of 69 SNPs predicted by consensus to be damaging across all platforms was identified. Mutpred and Fathmm identified 48 and 38 SNPs, respectively to be associated with cancer. While I- Mutant and MuPro assays suggested 22 SNPs to decrease protein stability. Additionally, these 22 SNPs reside within highly conserved regions of the BRCA2 protein. Domain analysis, utilizing InterPro, pinpointed 18 deleterious mutations within crucial DNA binding domains and one in the BRC repeat region. CONCLUSION: This study establishes a foundation for future experimental validations and the creation of breast cancer-targeted treatment approaches.

A Study on the Retrospective Reinterpretation of BRCA1 and BRCA2 Variants.

BACKGROUND: Hereditary breast/ovarian cancer is associated with BRCA gene mutations. As large volumes of clinical data on BRCA variants are continuously updated, their clinical interpretation may change, leading to their reclassification. This study analyzed the class and proportion of the changed clinical interpretations of BRCA variants to validate the need for periodic reviews of these variants. METHODS: This retrospective study reinterpreted previously reported BRCA1 and BRCA2 exon variants according to the 2015 American College of Medical Genetics and Genomics guidelines and the clinical significance of the recent public genomic database. Reanalyzed results were obtained for patients tested for BRCA genetic mutation for 10 years and 4 months. RESULTS: We included data from 4,058 patients, with 595 having at least one pathogenic variant (P), likely pathogenic variant (LP), or variant of uncertain significance (VUS) at a detection rate of 14.66%. The numbers of exon and intron variants were 562 (87.81%) and 78 (12.19%), respectively. BRCA1 exhibited a significantly higher P/LP detection rate of 6.96% compared to that of BRCA2 at 6.89% (p < 0.001). Conversely, BRCA2 demonstrated a significantly higher VUS rate of 10.38% compared to that of BRCA1 at 5.08% (p < 0.001). Among BRCA1 mutations, substitutions were the most prevalent in P/LP and VUS. Among BRCA2 mutations, deletions were most prevalent in P/LP, and substitutions were most prevalent in VUS. Among the 131 patients with P/LP in BRCA1 exons, the clinical interpretation was reclassified in two cases (1.53%), one VUS and one benign/likely benign (B/LB), and 48 cases (48.00%) with VUS were reclassified; one to P/LP and 47 to B/LB. Among the 138 patients with P/LP in BRCA2 exons, the clinical interpretation was reclassified in six (4.35%), five to VUS, and one to B/LB, and all 74 with VUS were reclassified to B/LB. CONCLUSIONS: We determined the class and proportion of reclassified BRCA variants. In conclusion, reviews are required to provide clinical guidance, such as determining treatment direction and preventive measures in the future.