Association of clinicopathologic and sonographic features with stromal tumor-infiltrating lymphocytes in triple-negative breast cancer.

BACKGROUND: Increased level of stromal tumor-infiltrating lymphocytes (sTILs) are associated with therapeutic outcomes and prognosis in triple-negative breast cancer (TNBC). This study aimed to investigate the associations of clinicopathologic and sonographic features with sTILs level in TNBC. METHODS: This study included invasive TNBC patients with postoperative evaluation of sTILs after surgical resection. Tumor shape, margin, orientation, echo pattern, posterior features, calcification, and vascularity were retrospectively evaluated. The patients were categorized into high-sTILs (≥ 20%) and low-sTILs (< 20%) level groups. Chi-square or Fisher's exact tests were used to assess the association of clinicopathologic and sonographic features with sTILs level. RESULTS: The 171 patients (mean ± SD age, 54.7 ± 10.3 years [range, 22‒87 years]) included 58.5% (100/171) with low-sTILs level and 41.5% (71/171) with high-sTILs level. The TNBC tumors with high-sTILs level were more likely to be no special type invasive carcinoma (p = 0.008), higher histologic grade (p = 0.029), higher Ki-67 proliferation rate (all p < 0.05), and lower frequency of associated DCIS component (p = 0.026). In addition, the TNBC tumors with high-sTILs level were more likely to be an oval or round shape (p = 0.001), parallel orientation (p = 0.011), circumscribed or micro-lobulated margins (p < 0.001), complex cystic and solid echo patterns (p = 0.001), posterior enhancement (p = 0.002), and less likely to have a heterogeneous pattern (p = 0.001) and no posterior features (p = 0.002). CONCLUSIONS: This preliminary study showed that preoperative sonographic characteristics could be helpful in distinguishing high-sTILs from low-sTILs in TNBC patients.

In silico analysis of potential inhibitors for breast cancer targeting 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1) catalyses.

Breast cancer (BC) is still one of the major issues in world health, especially for women, which necessitates innovative therapeutic strategies. In this study, we investigated the efficacy of retinoic acid derivatives as inhibitors of 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), which plays a crucial role in the biosynthesis and metabolism of oestrogen and thereby influences the progression of BC and, the main objective of this investigation is to identify the possible drug candidate against BC through computational drug design approach including PASS prediction, molecular docking, ADMET profiling, molecular dynamics simulations (MD) and density functional theory (DFT) calculations. The result has reported that total eight derivatives with high binding affinity and promising pharmacokinetic properties among 115 derivatives. In particular, ligands 04 and 07 exhibited a higher binding affinity with values of -9.9 kcal/mol and -9.1 kcal/mol, respectively, than the standard drug epirubicin hydrochloride, which had a binding affinity of -8.2 kcal/mol. The stability of the ligand-protein complexes was further confirmed by MD simulations over a 100-ns trajectory, which included assessments of hydrogen bonds, root mean square deviation (RMSD), root mean square Fluctuation (RMSF), dynamic cross-correlation matric (DCCM) and principal component analysis. The study emphasizes the need for experimental validation to confirm the therapeutic utility of these compounds. This study enhances the computational search for new BC drugs and establishes a solid foundation for subsequent experimental and clinical research.

Value of altered methylation patterns of genes RANBP3, LCP2 and GRAP2 in cfDNA in breast cancer diagnosis.

Background: The purpose of this study was to investigate the potential of plasma cfDNA methylation patterns in reflecting tumour methylation changes, focusing on three candidate sites, cg02469161, cg11528914, and cg20131654. These sites were selected for verification, with a particular emphasis on their association with breast cancer. Methods: We conducted a comprehensive analysis of 850k whole-methylation sequencing data to identify potential markers for breast cancer detection. Subsequently, we investigated the methylation status of the genes Ran-binding protein 3 (RANBP3), Lymphocyte cytoplasmic protein 2 (LCP2), and GRB2 related adaptor protein 2 (GRAP2), situated at the specified sites, using cancer and canceradjacent tissues from 17 breast cancer patients. We also examined the methylation patterns in different molecular subtypes and pathological grades of breast cancer. Additionally, we compared the methylation levels of these genes in plasma cfDNA to their performance in tissues. Results: Our analysis revealed that RANBP3, LCP2, and GRAP2 genes exhibited significant methylation differences between cancer and cancer-adjacent tissues. In breast cancer, these genes displayed diagnostic efficiencies of 91.0%, 90.6%, and 92.2%, respectively. Notably, RANBP3 showed a tendency towards lower methylation in HR+ breast cancer, and LCP2 methylation was correlated with tumour malignancy. Importantly, the methylation levels of these three genes in plasma cfDNA closely mirrored their tissue counterparts, with diagnostic efficiencies of 83.3%, 83.9%, and 77.6% for RANBP3, LCP2, and GRAP2, respectively. Conclusions: Our findings propose that the genes RANBP3, LCP2, and GRAP2, located at the identified methylation sites, hold significant potential as molecular markers in blood for the supplementary diagnosis of breast cancer. This study lays the groundwork for a more in-depth investigation into the changes in gene methylation patterns in circulating free DNA (cfDNA) for the early detection not only of breast cancer but also for various other types of cancer.

Crosstalk of methylation and tamoxifen in breast cancer (Review).

Tamoxifen is a widely used anti­estrogen drug in the endocrine therapy of breast cancer (BC). It blocks estrogen signaling by competitively binding to estrogen receptor α (ERα), thereby inhibiting the growth of BC cells. However, with the long­term application of tamoxifen, a subset of patients with BC have shown resistance to tamoxifen, which leads to low overall survival and progression­free survival. The molecular mechanism of resistance is mainly due to downregulation of ERα expression and abnormal activation of the PI3K/AKT/mTOR signaling pathway. Moreover, the downregulation of targeted gene expression mediated by DNA methylation is an important regulatory mode to control protein expression. In the present review, methylation and tamoxifen are briefly introduced, followed by a focus on the effect of methylation on tamoxifen resistance and sensitivity. Finally, the clinical application of methylation for tamoxifen is described, including its use as a prognostic indicator. Finally, it is hypothesized that when methylation is used in combination with tamoxifen, it could recover the resistance of tamoxifen.

Gene panel predicts neoadjuvant chemoimmunotherapy response and benefit from immunotherapy in HER2-negative breast cancer.

BACKGROUND: It is encountering the dilemma of lacking precise biomarkers to predict the response to neoadjuvant chemoimmunotherapy (NACI) and determine whether patients should use immune checkpoint inhibitors (ICIs) in early breast cancer (BC). We aimed to develop a gene signature to predict NACI response for BC patients and identify individuals suitable for adding ICIs. PATIENTS AND METHODS: Two I-SPY2 cohorts and one West China Hospital cohort of patients treated with NACI were included. Machine learning algorithms were used to identify key genes. Principal component analysis was used to calculate the ImPredict (IP) score. The interaction effects between biomarkers and treatment regimens were examined based on the logistic regression analysis. The relationship between the IP score and immune microenvironment was investigated through immunohistochemistry (IHC) and multiplex IHC. RESULTS: The area under the curves of the IP score were 0.935, 0.865, and 0.841 in the discovery cohort, validation cohort 1, and in-house cohort. Marker-treatment interaction tests indicated that the benefits from immunotherapy significantly varied between patients with high and low IP scores (p for interaction <0.001), and patients with high IP scores were more suitable for immunotherapy addition. CONCLUSIONS: Our IP model shows favorable performance in predicting NACI response and is an effective tool for identifying BC patients who will benefit from ICIs. It may help clinicians optimize treatment strategies and guide clinical decision-making.

Pharmacologic Hedgehog inhibition modulates the cytokine profile of osteolytic breast cancer cells.

The establishment and progression of bone metastatic breast cancer is supported by immunosuppressive myeloid populations that enable tumor growth by dampening the innate and adaptive immune response. Much work remains to understand how to target these tumor-myeloid interactions to improve treatment outcomes. Noncanonical Hedgehog signaling is an essential component of bone metastatic tumor progression, and prior literature suggests a potential role for Hedgehog signaling and its downstream effector Gli2 in modulating immune responses. In this work, we sought to identify if inhibition of noncanonical Hedgehog signaling alters the cytokine profile of osteolytic breast cancer cells and the subsequent communication between the tumor cells and myeloid cells. Examination of large patient databases revealed significant relationships between Gli2 expression and expression of markers of myeloid maturation and activation as well as cytokine expression. We found that treatment with HPI-1 reduced tumor cell expression of numerous cytokine genes, including CSF1, CSF2, and CSF3, as well as CCL2 and IL6. Secreted CSF-1 (M-CSF) was also reduced by treatment. Changes in tumor-secreted factors resulted in polarization of THP-1 monocytes toward a proinflammatory phenotype, characterized by increased CD14 and CD40 surface marker expression. We therefore propose M-CSF as a novel target of Hedgehog inhibition with potential future applications in altering the immune microenvironment in addition to its known roles in reducing tumor-induced bone disease.

Repositioning fluphenazine as a cuproptosis-dependent anti-breast cancer drug candidate based on TCGA database.

Breast cancer is one of the most prevalent malignancies among women. Enhancing the prognosis is an effective approach to enhance the survival rate of breast cancer. Cuproptosis, a copper-dependent programmed cell death process, has been associated with patient prognosis. Inducing cuproptosis is a promising approach for therapy. However, there is currently no anti-breast cancer drug that induces cuproptosis. In this study, we repositioned the clinical drug fluphenazine as a potential agent for breast cancer treatment by inducing cuproptosis. Firstly, we utilized the Cancer Genome Atlas (TCGA) database and Connectivity Map (CMap) database to identify 22 potential compounds with anti-breast cancer activity through inducing cuproptosis. Subsequently, our findings demonstrated that fluphenazine effectively suppressed the viability of MCF-7 cells. Fluphenazine also significantly inhibited the viability of triple negative breast cancer cells MDA-MB-453 and MDA-MB-231. Furthermore, our study revealed that fluphenazine significantly down-regulated the expression of potential prognostic biomarkers associated with cuproptosis, increased copper ion levels, and reduced intracellular pyruvate accumulation. Additionally, it up-regulated the expression of FDX1 at both the mRNA and protein levels, which has been reported to play a crucial role in the induction of cuproptosis. These findings suggest that fluphenazine has the potential to be used as an anti-breast cancer drug by inducing cuproptosis. Therefore, this research provides an insight for the development of novel cuproptosis-dependent anti-cancer agents.

Insights into the role of connexins and specialized intercellular communication pathways in breast cancer: Mechanisms and applications.

Gap junctions, membrane-based channels comprised of connexin proteins (Cxs), facilitate direct communication among neighbouring cells and between cells and the extracellular space through their hemichannels. The normal human breast expresses various Cxs family proteins, such as Cx43, Cx30, Cx32, Cx46, and Cx26, crucial for proper tissue development and function. These proteins play a significant role in breast cancer development, progression, and therapy response. In primary tumours, there is often a reduction and cytoplasmic mislocalization of Cx43 and Cx26, while metastatic lesions show an upregulation of these and other Cxs. Although existing research predominantly supports the tumour-suppressing role of Cxs in primary carcinomas through channel-dependent and independent functions, controversies persist regarding their involvement in the metastatic process. This review aims to provide an updated perspective on Cxs in human breast cancer, with a specific focus on intrinsic subtypes due to the heterogeneous nature of this disease. Additionally, the manuscript will explore the role of Cxs in immune interactions and novel forms of intercellular communication, such as tunneling nanotubes and extracellular vesicles, within the breast tumour context and tumour microenvironment. Recent findings suggest that Cxs hold potential as therapeutic targets for mitigating metastasis and drug resistance. Furthermore, they may serve as novel biomarkers for cancer prognosis, offering promising avenues for future research and clinical applications.

Causal role of blood metabolites in HER-positive and HER-negative breast cancer: a Mendelian randomization (MR) study.

BACKGROUND: Previous studies provide evidence that in vivo metabolites are associated with breast cancer (BC). However, the causal relationship between blood metabolites and BC remains unclear. METHOD: Comprehensive two-sample Mendelian randomization analysis was conducted to determine the causal association between 1400 publicly available genetic data on metabolic factors and human epidermal growth factor receptor positive (HER+) BC or HER- BC in this study. RESULT: Epiandrosterone sulfate levels (OR = 1.07, 95% CI = 1.02 ~ 1.10, p = 0.0013), 5alpha-androstan-3beta,17beta-diol monosulfate (2) levels (OR = 1.07, 95% CI = 1.03 ~ 1.12, p = 0.0012), glycohyocholate levels (OR = 0.85, 95% CI = 0.77 ~ 0.93, p = 0.0007) and etiocholanolone glucuronide levels (OR = 1.12, 95% CI = 1.05 ~ 1.20, p = 0.0013) were causally correlated with HER+ BC. 5 metabolites were causally correlated with HER- BC: Vanillic acid glycine levels (OR = 1.14, 95% CI = 1.06 ~ 1.22, p = 0.0003), Thyroxine levels (OR = 1.26, 95% CI = 1.11 ~ 1.44, p = 0.0004), 1-palmitoyl-2-linoleoyl-GPI (16:0/18:2) levels (OR = 0.86, 95% CI = 0.79 ~ 0.94, p = 0.0010), N-acetylphenylalanine levels (OR = 1.12, 95% CI = 1.05 ~ 1.19, p = 0.0007) and Glucose-to-mannose ratio (OR = 1.15, 95% CI = 1.06 ~ 1.24, p = 0.0008). Two common causally related metabolites were identified: Gamma-glutamyl glutamate and X-12849 levels. CONCLUSIONS: Our study has respectively demonstrated the connection between blood metabolites and HER+ or HER- BC by genetic means, thereby offering opportunities for therapeutic targets.

FBLN2 is associated with basal cell markers Krt14 and ITGB1 in mouse mammary epithelial cells and has a preferential expression in molecular subtypes of human breast cancer.

BACKGROUND: Fibulin-2 (FBLN2) is a secreted extracellular matrix (ECM) glycoprotein and has been identified in the mouse mammary gland, in cap cells of terminal end buds (TEBs) during puberty, and around myoepithelial cells during early pregnancy. It is required for basement membrane (BM) integrity in mammary epithelium, and its loss has been associated with human breast cancer invasion. Herein, we attempted to confirm the relevance of FBLN2 to myoepithelial phenotype in mammary epithelium and to assess its expression in molecular subtypes of human breast cancer. METHODS: The relationship between FBLN2 expression and epithelial markers was investigated in pubertal mouse mammary glands and the EpH4 mouse mammary epithelial cell line using immunohistochemistry, immunocytochemistry, and immunoblotting. Human breast cancer mRNA data from the METABRIC and TCGA datasets from Bioportal were analyzed to assess the association of Fbln2 expression with epithelial markers, and with molecular subtypes. Survival curves were generated using data from the METABRIC dataset and the KM databases. RESULTS: FBLN2 knockdown in mouse mammary epithelial cells was associated with a reduction in KRT14 and an increase in KRT18. Further, TGFß3 treatment resulted in the upregulation of FBLN2 in vitro. Meta-analyses of human breast cancer datasets from Bioportal showed a higher expression of Fbln2 mRNA in claudin-low, LumA, and normal-like breast cancers compared to LumB, Her2 +, and Basal-like subgroups. Fbln2 mRNA levels were positively associated with mesenchymal markers, myoepithelial markers, and markers of epithelial-mesenchymal transition. Higher expression of Fbln2 mRNA was associated with better prognosis in less advanced breast cancer and this pattern was reversed in more advanced lesions. CONCLUSION: With further validation, these observations may offer a molecular prognostic tool for human breast cancer for more personalized therapeutic approaches.

Induction of Cell Death by Bifidobacterium infantis DS1685 in Colorectal and Breast Cancers via SMAD4/TGF-Beta Activation.

Therapeutic advancements in treatments for cancer, a leading cause of mortality worldwide, have lagged behind the increasing incidence of this disease. There is a growing interest in multifaceted approaches for cancer treatment, such as chemotherapy, targeted therapy, and immunotherapy, but due to their low efficacy and severe side effects, there is a need for the development of new cancer therapies. Recently, the human microbiome, which is comprised of various microorganisms, has emerged as an important research field due to its potential impact on cancer treatment. Among these microorganisms, Bifidobacterium infantis has been shown to significantly improve the efficacy of various anticancer drugs. However, research on the role of B. infantis in cancer treatment remains insufficient. Thus, in this study, we explored the anticancer effect of treatment with B. infantis DS1685 supernatant (BI sup) in colorectal and breast cancer cell lines. Treatment with BI sup induced SMAD4 expression to suppress cell growth in colon and breast cancer cells. Furthermore, a decrease in tumor cohesion was observed through the disruption of the regulation of EMT-related genes by BI sup in 3D spheroid models. Based on these findings, we anticipate that BI sup could play an adjunctive role in cancer therapy, and future cotreatment of BI sup with various anticancer drugs may lead to synergistic effects in cancer treatment.

The deubiquitinating enzymes-related signature predicts the prognosis and immunotherapy response in breast cancer.

BACKGROUND: Breast cancer is a prevalent disease that has a dismal prognosis for patients and a bad outlook for treatments. Ubiquitination is a reversible biological process that regulates protein production and degradation, as well as plays a vital role in protein transport, localization, and biological activity. METHODS: We obtained the breast cancer patient sample data and used a machine learning technique to create a novel index called Deubiquitinating enzyme related index (DUBRI) by gathering genes associated to deubiquitinating enzymes. Based on DUBRI, we systematically analyze patients' prognosis, clinical characteristics, tumor immune microenvironment, chemotherapy response and immunotherapy response. Finally, the function of OTUB2 was explored in breast cancer cells. RESULTS: DUBRI, which consists of five deubiquitinating enzyme genes (OTUB2, USP41, MINDY2, YOD1, and PSMD7), is a reliable predictor of survival in breast cancer patients. We found that the high DUBRI group presented higher levels of immune cell infiltration. We performed molecular docking prediction of core target proteins in deubiquitinating enzymes. In vitro experiments verified that knockdown of OTUB2 could inhibit the proliferation and migration of breast cancer. CONCLUSIONS: The DUBRI discovered in this research may effectively evaluate the outlook of breast cancer patients and identify groups of patients who would gain advantages from immunotherapy, offering vital knowledge for the future targeted treatment of breast cancer patients.

Integrated nomogram to predict HER2 expression in breast tumor: Clinical, Ultrasound, and Photoacoustic imaging approaches.

BACKGROUND: HER2 is a key biomarker for breast cancer treatment and prognosis. Traditional assessment methods like immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are effective but costly and time-consuming. Our model incorporates these methods alongside photoacoustic imaging to enhance diagnostic accuracy and provide more comprehensive clinical insights. MATERIALS AND METHODS: A total of 301 breast tumors were included in this study, divided into HER2-positive (3+ or 2+ with gene amplification) and HER2-negative (below 3+ and 2+ without gene amplification) groups. Samples were split into training and validation sets in a 7:3 ratio. Statistical analyses involved t-tests, chi-square tests, and rank-sum tests. Predictive factors were identified using univariate and multivariate logistic regression, leading to the creation of three models: ModA (clinical factors only), ModB (clinical plus ultrasound factors), and ModC (clinical, ultrasound, and photoacoustic imaging-derived oxygen saturation (SO2)). RESULTS: The area under the curve (AUC) for ModA was 0.756 (95 % CI: 0.69-0.82), ModB increased to 0.866 (95 % CI: 0.82-0.91), and ModC showed the highest performance with an AUC of 0.877 (95 % CI: 0.83-0.92). These results indicate that the comprehensive model combining clinical, ultrasound, and photoacoustic imaging data (ModC) performed best in predicting HER2 expression. CONCLUSION: The findings suggest that integrating clinical, ultrasound, and photoacoustic imaging data significantly enhances the accuracy of predicting HER2 expression. For personalised breast cancer treatment, the integrated model could provide a comprehensive and reproducible decision support tool.

LYMPH-Q translation, cultural adaptation and validation in Italian language: A prospective PROMs-based study on breast cancer-related arm lymphedema for patients' education.

BACKGROUND: Upper Extremity Lymphedema following oncological breast surgery affects not only the patient's physique, but also the patient's psychological sphere. One of the best known PROMs-based questionnaires for investigating the condition is the LYMPH-Q. The study aimed to perform the Italian translation and cultural adaptation of the LYMPH-Q and to assess if, independently from disease evolution, arm sleeve improves QoL in these patients. MATERIALS AND METHODS: Translation included 4 steps: Forward translation, Back translation, Back translation review and Patient interviews. The questionnaire was administered to 50 female patients older than 18 years of age with UEL who received a prescription for daily use of a compression sheath. A second administration took place 30 days after. Forty-four patients completed the study (Group 1: 26 patients with indication to use compression sleeve who wore it; Group 2:18 patients who despite the prescription did not want to wear it. A descriptive statistical analysis was performed with Prism 9 software. RESULTS: T-tests showed statistical significance for changes in "Symptoms," "Function," "Appearance" and "Psychological" scales. There were no statistically significant changes for "Information scale" in Group 1 and for all scales in Group 2. CONCLUSION: Data from this observational study show that HR-QOL analyzed from the patients' perspective also tends to improve in terms of symptoms, function, appearance, and psychological sphere in patients with BCRL when using a compression sheath. The Lymph-Q has proven to be a valuable ally of the physician attempting to improve treatment approaches for BCRL based not only on scientific evidence but also on PROMs.

The associations of emotion regulation, self-compassion, and perceived lifestyle discrepancy with breast cancer survivors' healthy lifestyle maintenance.

PURPOSE: Unhealthy lifestyle increases the risk of comorbidities, reduced quality of life, and cancer recurrence among breast cancer survivors. It is important to identify emotional and cognitive factors that may affect the maintenance of a healthy lifestyle over time. This study examined the associations of perceived lifestyle discrepancy, self-compassion, and emotional distress with the maintenance of a healthy lifestyle among breast cancer survivors and the mediating role of emotion regulation patterns (cognitive reappraisal and expressive suppression) in these associations. METHODS: A total of 145 female breast cancer survivors aged 31-77 completed self-reports on healthy lifestyle maintenance, perceived lifestyle discrepancy, self-compassion, emotional distress, and emotion regulation patterns. Structural equation modeling was used to analyze the data. RESULTS: Mean physical activity and healthy diet maintenance scores were moderate. The structural equation modeling analysis showed good fit indicators (χ2 = 4.21, df = 10, p = .94; χ2/df = 0.42; NFI = .98; TLI = 1.09; CFI = 1.00; RMSEA = .00, 95% CI (.00, .02)). Lower perceived lifestyle discrepancy was directly associated with higher physical activity (ß = -.34, p < .01) and healthy diet (ß =-.39, p < .01). Cognitive reappraisal was associated with higher physical activity (ß = .19, p < .01), and expressive suppression was associated with lower physical activity (ß = -.19, p < .01), and both mediated the association between self-compassion and physical activity. CONCLUSIONS: The mediated associations reported in this study indicate that psychosocial factors, especially self-compassion, perceived lifestyle discrepancy, and emotional regulation patterns, are relevant to healthy lifestyle maintenance among breast cancer survivors, because solely providing healthy lifestyle recommendations does not motivate individuals to adhere to them. IMPLICATIONS FOR CANCER SURVIVORS: Short-term structured psychosocial interventions designed to reduce perceived health discrepancy and strengthen self-compassion should be implemented and their effect on lifestyle should be further evaluated.

Insights into the Refusal of Free Screening Mammograms: Exploring Contributing Factors.

Background: Despite the availability of free screening mammograms (SMG) through the Breast Cancer Early Detection (BCED) Program in the Qassim region of Saudi Arabia, a notable gap exists between program implementation and the actual uptake of SMG. This study aims to assess the refusal rate, identify barriers to participation, and shed light on the factors influencing women's decisions regarding SMG. Methods: A cross-sectional study was conducted among consecutive women aged 40-69 participating anonymously in the BCED program in September 2023. The participants were administered a validated Arabic language survey encompassing breast cancer screening backgrounds and knowledge, reasons for refusal, and factors influencing SMG reconsideration. Logistic regression was employed to identify factors linked with SMG refusal using SPSS version 28. Results: Of the 2446 eligible women in the study, 576 (23.6%) declined to undergo SMG. The median age of participants was 49 years, primarily married (91.5%) and residing in central cities (60.3%). Previous mammogram history was reported by 21.4%, with only 12.9% performing regular SMGs every 1-2 years. Married women had a 31% lower refusal likelihood to SMG compared to widowed/divorced women (Adjusted Odds Ratio [aOR] = 0.69, p = 0.02). Women residing in peripheral areas showed approximately 1.45 times higher odds of refusal compared to those in central cities (aOR = 1.45, p < 0.001), and women without prior history of SMG had 2.13 times higher odds of refusal (aOR = 2.14, p < 0.001). Conclusion: The refusal rate for SMG in the Qassim region aligns closely with rates observed in developed countries. Despite this progress, significant barriers to SMG uptake persist, and tailored interventions targeting specific demographic groups and addressing these barriers are essential to improving screening participation, promoting a culture of proactive screening behavior, and ensuring equitable access to screening services for all eligible women.

Barriers to Breast Cancer Screening in Saudi Arabia: A Systematic Review and Meta-Analysis.

Breast cancer is a significant public health concern globally, and early detection through screening programs can improve treatment outcomes and reduce mortality rates. However, the uptake of breast cancer screening among women in Saudi Arabia is hindered by various barriers. This systematic review and meta-analysis aimed to elucidate the barriers to breast cancer screening among women in Saudi Arabia, providing insights into the multifaceted challenges hindering screening uptake and informing tailored interventions and policy recommendations. A comprehensive literature search was conducted across electronic databases and grey literature sources to identify relevant studies on barriers to breast cancer screening in Saudi Arabia. Studies conducted between 2017 and 2023, employing diverse settings and methodologies, were included in the analysis. Data on the prevalence of barriers, family history of breast cancer, and self-reported breast examination practices were extracted and synthesized. A total of 14 studies met the inclusion criteria, encompassing diverse populations and methodologies. The included studies predominantly employed cross-sectional survey designs and targeted various populations across different regions of Saudi Arabia. The barriers to breast cancer screening were investigated, revealing concerns such as fear of discovering cancer, embarrassment due to breast-related tests, fear of pain related to clinical examination, and lack of awareness. Additionally, a substantial proportion of participants reported a family history of breast cancer, indicating a significant risk factor for the disease. Self-reported breast examination practices varied among participants, with disparities in screening behaviors observed. Our review identified fear of diagnosis, embarrassment, and lack of awareness as key barriers to breast cancer screening in Saudi Arabia. Targeted interventions, including education and improved access, are essential to address these challenges and enhance early detection efforts, reducing the burden of breast cancer.

Metastasis of breast cancer to the thyroid gland.

Metastases to the thyroid gland from nonthyroidal malignant tumors are rare but significant. They are often asymptomatic, indicating advanced-stage primary tumors and poor prognosis. Although infrequently, breast cancer (BC) can metastasize to the thyroid gland. We present the case of a 56-year-old woman with a history of BC who presented with a nodular goiter. Physical examination and imaging revealed a thyroid nodule and cervical lymph nodes with suspicious features. Fine-needle aspiration biopsy (FNAB) confirmed the presence of atypical epithelial cells in the thyroid nodule and lymph nodes. Further evaluation, including positron emission tomography, histological biopsy, and immunohistochemistry, supported the diagnosis of metastatic BC to the thyroid gland. Due to the local extent of the disease, total thyroidectomy was not feasible. The treatment with ribociclib and letrozole was initiated, but unfortunately, the patient had an unfavorable progression with the development of metastasis in the nervous system. Metastatic carcinoma to the thyroid gland is rare but has increased due to improved diagnostic techniques. BC can metastasize to the thyroid. Diagnosis involves imaging, FNAB, and immunohistochemistry. Treatment options include surgery, radiotherapy, and chemotherapy, but the prognosis is generally poor.

Las metástasis en la glándula tiroides a partir de tumores malignos no tiroideos son raras pero significativas. A menudo son asintomáticas, lo que indica tumores primarios en etapas avanzadas y un mal pronóstico. Aunque infrecuentemente, el cáncer de mama puede metastatizar en la glándula tiroides. Presentamos el caso de una mujer de 56 años con antecedente de cáncer de mama que consultó por bocio nodular. El examen físico y las imágenes revelaron un nódulo tiroideo y ganglios linfáticos cervicales con características sospechosas. La punción aspiración con aguja fina confirmó la presencia de células epiteliales atípicas en el nódulo tiroideo y los ganglios linfáticos. Una evaluación adicional, que incluyó tomografía por emisión de positrones, biopsia histológica e inmunohistoquímica, respaldó el diagnóstico de cáncer de mama metastásico en la glándula tiroides. Debido a la extensión local de la enfermedad, no fue factible realizar una tiroidectomía total. Se inició el tratamiento con ribociclib y letrozol, pero desafortunadamente la paciente tuvo una progresión desfavorable con el desarrollo de metástasis en el sistema nervioso. El carcinoma metastásico en la glándula tiroides es raro, pero ha aumentado debido a las técnicas de diagnóstico mejoradas. El cáncer de mama puede metastatizar en la tiroides. El diagnóstico implica imágenes, punción aspiración con aguja fina e inmunohistoquímica. Las opciones de tratamiento incluyen cirugía, radioterapia y quimioterapia, pero el pronóstico generalmente es desfavorable.

Bioinformatics and computational studies of chabamide F and chabamide G for breast cancer and their probable mechanisms of action.

Globally, the prevalence of breast cancer (BC) is increasing at an alarming level, despite early detection and technological improvements. Alkaloids are diverse chemical groups, and many within this class have been reported as potential anticancer compounds. Chabamide F (F) and chabamide G (G) are two dimeric amide alkaloids found in a traditional medicinal plant, Piper chaba, and possess significant cytotoxic effects. However, their scientific rationalization in BC remains unknown. Here, we aimed to investigate their potential and molecular mechanisms for BC through in silico approaches. From network pharmacology, we identified 64 BC-related genes as targets. GO and KEGG studies showed that they were involved in various biological processes and mostly expressed in BC-related pathways such as RAS, PI3K-AKT, estrogen, MAPK, and FoxO pathways. However, PPI analysis revealed SRC and AKT1 as hub genes, which play key roles in BC tumorigenesis and metastasis. Molecular docking revealed the strong binding affinity of F (- 10.7 kcal/mol) and G (- 9.4 and - 11.7 kcal/mol) for SRC and AKT1, respectively, as well as the acquisition of vital residues to inhibit them. Their long-term stability was evaluated using 200 ns molecular dynamics simulation. The RMSD, RMSF, Rg, and SASA analyses showed that the G-SRC and G-AKT1 complexes were excellently stable compared to the control, dasatinib, and capivasertib, respectively. Additionally, the PCA and DCCM analyses revealed a significant reduction in the residual correlation and motions. By contrast, the stability of the F-SRC complex was greater than that of the control, whereas it was moderately stable in complex with AKT1. The MMPBSA analysis demonstrated higher binding energies for both compounds than the controls. In particular, the binding energy of G for SRC and AKT1 was - 120.671 ± 16.997 and - 130.437 ± 19.111 kJ/mol, respectively, which was approximately twice as high as the control molecules. Van der Waal and polar solvation energies significantly contributed to this energy. Furthermore, both of them exhibited significant interactions with the binding site residues of both proteins. In summary, this study indicates that these two molecules could be a potential ATP-competitive inhibitor of SRC and an allosteric inhibitor of AKT1.