Treatment Of Breast Cancer Research Articles

UGCG promotes chemoresistance and breast cancer progression via NF-κB and Wnt/β-catenin pathway activation.

Taxane-based chemotherapy is the primary treatment for triple-negative breast cancer (TNBC), yet clinical outcomes remain unsatisfactory due to the persistence of chemoresistance. Identifying key factors that contribute to chemoresistance and understanding the associated molecular mechanisms is therefore essential. The GEO databases were utilized to pinpoint factors related to chemoresistance, which were subsequently validated using clinical tissue samples. The role of UGCG in the malignant progression and chemoresistance of TNBC was assessed through various functional assays. Western blotting, qRT-PCR, and immunohistochemistry were employed to investigate the signaling pathways associated with UGCG in TNBC. UGCG expression was notably elevated in chemoresistant breast cancer tissues and cells, as identified in GEO databases and confirmed through immunohistochemistry. Additionally, findings from our cohorts indicated that higher levels of UGCG expression correlated with a lower rate of pathological complete response (pCR), suggesting it could serve as an independent predictor of chemotherapy effectiveness. Gain- and loss-of-function experiments demonstrated that UGCG enhanced the proliferation, metastasis, and stemness of breast cancer cells. Furthermore, treatment with paclitaxel or docetaxel resulted in increased UGCG expression, which in turn reduced chemotherapy-induced cell apoptosis and improved drug resistance and metastatic capabilities. Mechanistically, UGCG was found to amplify the activation of NF-κB and Wnt/β-catenin pathways, and the use of inhibitors targeting these pathways diminished the UGCG-induced malignant effects. Our findings underscore the significant role of UGCG in the chemoresistance and progression of breast cancer, suggesting it as a predictive biomarker and potential therapeutic target to combat chemoresistance in this disease.

Implementation of model-informed precision dosing for tamoxifen therapy in patients with breast cancer: A prospective intervention study.

Tamoxifen is an estrogen-receptor (ER) antagonist, used as adjuvant treatment of ER-positive breast cancer. It is converted by CYP2D6 into endoxifen, its most active metabolite. Patients with endoxifen plasma concentrations <16nM face a higher risk of recurrence. The use of a priori model-informed precision dosing (MIPD) may lead to faster target attainment and thus potentially improve patient outcomes. In total, 106 evaluable patients were prospectively included in this single-arm MIPD-intervention study. Patients received a model-predicted tamoxifen dose when starting tamoxifen-treatment (65.1% of patients received 20mg, 16.0% received 30mg and 18.9% received 40mg). Seventy-five percent of the 40mg group was predicted to be unable to reach the threshold of 16nM despite receiving the highest registered dose. After attaining steady-state, 84.0% of patients reached endoxifen levels ≥16nM, which was not significantly higher compared to a historical control cohort (77.9%, p=0.17). The model showed adequate performance and correctly identified patients requiring 40mg tamoxifen. Endoxifen samples that were acquired 4-6 weeks after treatment initiation, are informative of steady-state endoxifen levels and can be used to inform MIPD and adjust tamoxifen dosing prior to steady-state attainment. In this first MIPD implementation study for patients treated with tamoxifen, MIPD did lead to more patients achieving endoxifen levels ≥16nM as compared to the one-dose-fits-all strategy, albeit insignificant. This may partly be explained by a larger proportion of patients who were recommended to switch to an aromatase inhibitor (AI) in the intervention cohort. In conclusion, MIPD seems beneficial compared to one-size-fits-all-dosing, but TDM still remains an important addition.

Therapeutic strategies and landscape of metaplastic breast cancer.

Metaplastic breast cancer is a rare and heterogeneous subtype of breast cancer, associated with a poor prognosis. Its distinct biological behavior and morphological features contribute to resistance to standard treatment regimens. Hitherto, the optimal therapeutic strategy for metaplastic breast cancer remains underexplored. Herein, we review the literature on the treatment of metaplastic breast cancer, summarizing current local and systemic therapies, and discuss potential therapeutic targets and novel strategies based on its pathological and molecular characteristics. Targeted therapy and immunotherapy may provide more personalized treatment options, with the potential to improve the prognosis of this disease.

Analysing the apoptotic potential of green synthesized Nyctanthes arbor-tristis chitosan nanoparticles in MDA-MB-231 and SKOV3 cell lines

Gynecological tumors are highly aggressive cancers in women, often treated with conventional treatments that can cause significant side effects. This study focuses on the preparation of chitosan nanoparticles from Nyctanthes arbor-tristis leaves, which possess anti-tumor properties, to address and overcome these issues. The successfully synthesized nanoparticles were characterized by UV-spectroscopy, DLS, TEM, and FTIR spectroscopy to analyze their physiochemical properties. In vitro studies, including cytotoxicity and scratch wound healing assays, along with staining and qRT-PCR, revealed the nanoparticles' anticancer efficacy against breast and ovarian cancer cells. The formation of Nat-CSNPs showed an absorbance peak at 221nm, a particle size range of 41-56nm with a spherical shape, polydispersity, and a positive surface charge. FTIR spectroscopy demonstrated the presence of functional groups associated with the synthesized Nat-CSNPs. It exhibited dose-dependent cytotoxicity, with IC50 values of 62.40μg/ml for MDA-MB-231 and 44.7μg/ml for SKOV3 cells. Further assays such as wound healing assay, and DAPI/AO/EtBr staining demonstrated their antiproliferative and apoptotic effects on MDA-MB-231 and SKOV3 cells. Induction of apoptosis by the chitosan-nanoparticle via upregulation of the pro-apoptotic genes (Bax, Cas3, Cas9) and downregulation of antiapoptotic genes (Bcl2) was assessed using qRT-PCR analysis. In vivo acute toxicity assessments of Nat-CSNPs on Danio rerio revealed no significant impact on glucose levels or AST, ALT, and AChE activity, indicating low toxicity. These findings underscore the potent anticancer effects of Nat-CSNPs, particularly inducing apoptosis in MDA-MB-231 and SKOV3 cell lines. While demonstrating low toxicity in Danio rerio, Nat-CSNPs are considered a promising novel anti-cancer drug for breast and ovarian cancer treatment.

In Silico Studies of Phytoconstituents to Identify Potential Inhibitors for ERα Protein of Breast Cancer

Background: It is noteworthy that a wide array of plants and nutraceuticals are effectively utilized in the treatment of various cancers, demonstrating potent effects on different cancer targets with fewer side effects. Notably, estrogen alpha has been identified as a crucial factor in breast cancer cell proliferation. Agents that can antagonize its action hold promise as potential drug leads for the treatment of breast cancer. Objective: This study aims to discover and identify the potential inhibitors against the most influential ERα receptor by the computational approach of 134 phytochemicals from 17 medicinal plants by using in silico docking studies. Methods: The molecular docking was performed by a genetic algorithm using the Auto Dock Vina program, and the validation of docking was also performed by using Molecular Dynamic (MD) simulation by the Desmond tool of Schrödinger molecular modeling. Drug-likeness properties and toxicity studies were conducted using SWISS PRO. Results: The top ten highest binding energy phytochemicals ginicidin (-10.8 kcal/mol), lemairone (-10.5 kcal/mol), ixoratannin (-10.0 kcal/mol), hydnocarpine (-9.8 kcal/mol), arabelline (-9.8 kcal/mol), acutilobine E (-9.8 kcal/mol), chaparinone (-8.9 kcal/mol), plumieride coumerate (-8.8 kcal/mol), acutilobine C (-8.7 kcal/mol), and mezerein (-8.7 kcal/mol) were taken for drug-likeness test and ADMET profile prediction with the help of web-based server SWISS ADME and protoxII. Docking's study dictated that ten phytochemical constituents showed greater binding interactions than standard tamoxifen (-6.6 kcal/mol) towards the target protein ERα. MSD study was achieved for the most active 4 phytoconstituents, and the stability of the ligand-protein complex was confirmed and showed that all the four compounds possess comparatively stable ligand-protein complexes with ERα target as compared to the tamoxifen-ERα complex. Conclusion: Among the top ten phytochemicals, ginicidin (glycoside) formed a more stable complex and had greater binding affinity than standard tamoxifen with better safety profiles. Hence, this compound can be further studied for lead optimization and drug development for the treatment of breast cancer.

Curcumin modified Fe3O4 with efficient SDT for the treatment of breast cancer

Sonodynamic therapy (SDT) is a non-invasive anti-tumor strategy with good efficacy, strong penetration and few side effects. However, the microenvironment of tumor hypoxia and high expression of hydrogen peroxide (H2O2) limits the efficiency of SDT. In this work, we have prepared a ultrasound-enhanced anti-tumor material by hydrothermal method, and the nanomaterials with optimal catalytic ability are identified by controlling the quality of curcumin (Fe3O4/Cur). The Fe3O4/Cur is not only capable of generating ROS by ultrasound excitation, but also generates ROS by the Fenton reaction with H2O2, and the SDT effect of Fe3O4/Cur is further enhanced. Under ultrasound stimulation, the Fe3O4/Cur can effectively kill the breast cancer cells within 15 min. This work provides a new idea for the treatment of breast cancer.

Design and implication of a breast cancer-targeted drug delivery system utilizing the Kisspeptin/GPR54 system.

Kisspeptins function as endogenous ligands for the G protein-coupled receptor GPR54. While the primary role of the Kisspeptin/GPR54 signaling pathway pertains to reproduction, several studies have shown that GPR54 is highly expressed in breast cancer, and we further confirmed this result that GPR54 expression is significantly upregulated in breast cancer cells. Based on this finding, we developed a liposomal drug delivery system utilizing the Kisspeptin/GPR54 system to treat breast cancer after confirming the safety of Kp-10-228. By surface-modifying liposomes with Kp-10-228 (228-K3-EG8-Liposome), we demonstrated enhanced accumulation of these liposomes in tumor cells, both in vitro and in vivo. Doxorubicin-loaded 228-K3-EG8-Liposome exhibited a remarkable inhibition of cancer cell proliferation, significantly extending the median survival time in mice with breast tumors compared to model mice treated with non-targeted liposomes or free doxorubicin. Our results suggest that the liposomal drug delivery system utilizing the Kisspeptin/GPR54 system is a promising novel strategy for the management of breast cancer.

Two sides of the same coin-sexuality from the perspective of women diagnosed with breast cancer and their partners: A qualitative study.

After the diagnosis of breast cancer, women's sexuality becomes complex, and the sexual lives of couples are strongly affected by the treatment process of the disease. The aim of this study is to determine the perceptions, experiences, expectations, and needs related to sexuality from the perspective of women diagnosed with breast cancer and their partners. In this study, a descriptive qualitative design based on a thematic analysis approach was used. The data were collected through individual semi-structured interviews with women diagnosed with breast cancer (n=22) and their partners (n=14). The thematic analysis approach was used to analyse the data. The main themes of this study that came out from both the patients' and partners' perspectives were 'suspension (postponement) of sexual life' and 'unmet need for care related to sexuality'. The main themes consist of four sub-themes: 'changes in sexual dynamics', 'unsatisfied sexuality', 'barriers to accessing information and support', and 'demand for individualised and tailored comprehensive counselling'. Women with breast cancer and their partners were found to have difficulty in asking for help about sexuality and to postpone their sexual lives. Findings of the present study suggest that sexual counselling is of critical importance at every stage of the breast cancer treatment process, and the patients and their partners need a culturally sensitive, individualised care thereof and expect a continuous support.

Association between chemotherapy and the risk of developing breast cancer-related lymphedema: a nationwide retrospective cohort study.

Breast cancer-related lymphedema (BCRL) is a well-known complication of breast cancer treatment, which often includes chemotherapy. This study aimed to investigate the association between chemotherapy and the risk of developing BCRL in patients with new-onset breast cancer. This nationwide retrospective cohort study utilized data from the Korean National Health Insurance database and the Korea National Cancer Incidence Database (2006-2017). Using 1:1 propensity score matching, 37,202 participants who received chemotherapy and 37,202 who did not receive chemotherapy were included in the analysis. Cox proportional hazard regression models were employed to examine the association between chemotherapy and the risk of developing BCRL. Among the 74,404 participants, 11,508 (15.5%) were diagnosed with BCRL during the follow-up period. Compared with patients who did not receive chemotherapy, the risk of BCRL was higher in patients undergoing chemotherapy (hazard ratio [95% confidence interval]: 1.95 [1.87-2.04]). Furthermore, compared to patients who did not receive chemotherapy, the risk of BCRL was confirmed in the taxane (3.38 [3.19-3.58]), antimetabolite (1.79 [1.67-1.91]), and anthracycline (1.49 [1.41-1.56]) chemotherapy groups. Chemotherapy administration following a diagnosis of breast cancer increases the risk of BCRL. Therefore, vigilant monitoring for BCRL, particularly in patients undergoing chemotherapy with taxanes, antimetabolites, or anthracyclines, is warranted during follow-up.

Microfluidic fabrication of lipid nanoparticles for co-delivery of siRNA and hydroxychloroquine: An engineered theranostic platform for enhanced breast cancer treatment

Microfluidic fabrication of lipid nanoparticles for co-delivery of siRNA and hydroxychloroquine: An engineered theranostic platform for enhanced breast cancer treatment

Influence of the ERK/CHGB pathway in breast cancer progression under chronic stress.

Breast cancer is one of the most common malignancies among women, and its development involves a variety of complex molecular mechanisms. Extracellular signal-regulated kinase (ERK) and Chromogranin B (CHGB) are known to play key roles in various cancers. This study aims to explore the impact of the ERK/CHGB pathway in a chronic stress environment simulated by salbutamol on the development of breast cancer. This study utilized female BALB/c mice to establish a breast cancer model, dividing them into control, salbutamol-treated, and salbutamol-inhibitor-treated groups. Cell culture, immunohistochemistry, Western Blot, real-time fluorescent quantitative PCR, and Transwell migration assays were employed to assess the effects of salbutamol and the ERK/CHGB pathway. Salbutamol treatment significantly enhanced the proliferation, migration, and invasiveness of breast cancer cells, associated with the activation of the ERK pathway and the inhibition of CHGB. The salbutamol-inhibitor-treated group exhibited a marked suppression of these effects. Additionally, the interaction of the ERK/CHGB pathway in an extracellular stress environment provided advantages for the survival and proliferation of breast cancer cells. This study demonstrates that a chronic stress environment simulated by salbutamol can promote malignant behaviors in breast cancer cells through the ERK/CHGB pathway. These findings offer new molecular targets for breast cancer treatment and highlight the potential importance of managing chronic stress and blocking specific molecular pathways in cancer therapy.

Identification of 8-(2-methyl phenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a novel and selective TGFβ RII kinase inhibitor for breast cancer therapy.

Transforming growth factor-beta (TGF-β) plays a pivotal role in breast development by modulating tissue composition during the developmental phase. The TGFβ type II receptor (TGFβ RII) is implicated in breast cancer and represents a valuable therapeutic target. Due to the off-target side effects of many existing TGFβI/TGFβ RII inhibitors, a more targeted approach to drug discovery is necessary. This study used computational modeling and molecular dynamics simulations to screen the ChemBridge small molecule library against TGFβ RII. This study employed high-throughput virtual screening, molecular dynamics simulations, and binding free energy calculations to identify potential inhibitors targeting TGF-β RII. MDA-MB 231 and MCF-7 breast cancer cells were used in anti-proliferative, tans-endothelial migration, and flow cytometric assays for in vitro validations. We identified 8-(2-methylphenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a potent and selective inhibitor. Protein-ligand modeling analysis revealed that C-5635020 targets the kinase domain of TGFβ RII with superior binding affinities compared to the standard drug, staurosporine. Computational results suggest that C-5635020 selectively binds and inhibits TGFβ RII activity, thereby controlling cell proliferation in breast cancer. In vitro, experiments corroborated these predictions, where C-5635020 inhibited TGFβ RII and p-Smad 2/3 positive population in MDAMB-231 and MCF-7cells. The compound dose-dependently inhibited cell proliferation, trans-endothelial migration, and increased apoptosis in both breast cancer cell lines. The strong binding affinity, stability, and favorable thermodynamics of C-5635020 with established in vitro efficacy highlight its potential as a lead compound for further preclinical and clinical developments for breast cancer treatment.

Molecular Dynamics of Breast Cancer Subtypes: The Role of FAM83H-AS1 Long Non-coding RNA in Breast Cancer Metastasis.

Breast cancer is the leading cause of cancer-related deaths in women. Long non-coding RNAs (lncRNAs) play an important role in gene regulation and are emerging as major players in cancer biology, This study investigates the expression of FAM83H-AS1 in breast cancer and its association with tumor grade, hormone receptors, pathological diagnosis, and molecular markers related to epithelial-mesenchymal transition (EMT). The expression of the long non-coding RNA FAM83H-AS1 in 80 breast cancer patients was assessed using quantitative real-time PCR (qRT-PCR). Clinical significance was evaluated through histopathological and immunohistochemical analyses. The associations of FAM83H-AS1 expression with tumor grade, hormone receptor status, and epithelial-mesenchymal transition (EMT) markers were analyzed. A positive correlation was observed between tumor grade and the expression of FAM83H-AS1, N-cadherin, E-cadherin, and vimentin, whereas FGF-18, TGF-β, and β-catenin were downregulated. Estrogen receptor positivity was associated with CLDN1 and Snail-1 expression, while HER2 positivity was linked to vimentin expression. Snail-1 expression correlated positively with Ki-67 levels. All genes except MMP2 were significantly associated with lymph node metastasis. Comparative analysis revealed significant differences in FGF-18, TGF-β, N-cadherin, β-catenin, and MMP2 expression among luminal A, luminal B, and triple-negative breast cancer (TNBC) subtypes. FAM83H-AS1 was upregulated in TNBC compared to luminal A and inflammatory breast cancer (IBC), although the difference was not statistically significant. TNBC Exhibited upregulation of TGF-β, N-cadherin, and β-catenin, suggesting their role in the aggressive nature of this subtype. In contrast, MMP2 was downregulated in TNBC compared to IBC, potentially indicating a suppressive role in tumor invasion in TNBC. Vimentin was upregulated in IBC compared to luminal A, indicating its involvement in IBC's aggressive behavior. MMP2 and MMP9 were significantly upregulated in IBC compared to luminal A. FAM83H-AS1 shows potential as a prognostic biomarker and therapeutic target, especially in TNBC and IBC, with implications for personalized breast cancer treatment strategies. Its expression correlates with tumor grade, hormone receptor status, and EMT markers, suggesting a role in cancer progression and metastasis.

Curcumin chemo-sensitizes intrinsic apoptosis through ROS-mediated mitochondrial hyperpolarization and DNA damage in breast cancer cells.

Curcumin (CUR), a polyphenol phyto-compound extracted from turmeric rhizome (Curcuma longa), suppresses cancer by inducing apoptosis while also limiting cell survival and proliferation. This in vitro and in silico research work focuses on the synergistic sensitization of Doxorubicin (DOXO) on regulating ROS-mediated apoptosis of the breast cancer cells (MDA-MB-231 and MCF-7) in DOXO-CUR co-treatment. We observed dose-dependent cytotoxicity, increased ROS production, and mtDNA fragmentation by reduced membrane potential. The combined molecular docking of Bcl2, Bax, and Caspase3 proteins with DOXO and CUR with lower binding energies proves the stable interactions of protein-ligand complexes in the combination doses. Cell survival was measured by MTT and flow cytometry assays. Mitochondrial ROS production, mtDNA condensation, and MMP depletion were documented using fluorescence micrographs. The enrichment analysis of the ROS pathway genes by RT-qPCR (relative fold change) indicates the activation of Caspase3-mediated intrinsic apoptosis. Autodock 4.2 and Gromac 2022.4 were performed for in silico binding interaction and stability analysis. Our study calculates the DOXO and CUR combination (0.33 + 33 μM in MDA-MB-231 and 0.14 + 14 μM in MCF-7) shows maximum growth inhibition (70-75 %) by elevated oxidative stress and reduced membrane potential, which suggests that CUR could be a potential therapeutic agent for treating breast cancers in near future. The method of apoptosis was further analyzed, where elevated cellular ROS level by CUR + DOXO combination therapy depleted mitochondrial membrane potential and enhanced the DNA condensation. The mitochondrial pro-apoptotic genes BAX, BAK, BIM, CASPASE9, and CASPASE3 and anti-apoptotic BCL2 gene expressions depicted triggering intrinsic apoptosis pathway, co-relating with the in silico molecular docking, simulation, and MM-PBSA energy calculations. The synergism between CUR and DOXO was also validated by increased binding affinity and reduced inhibitory constant against key proteins Bcl2, Bax, and Caspase3. Bcl2-DOXO showed BE: -5.03 and Bcl2-DOXO-CUR showed BE: -4.7. Whereas, Bax-DOXO binding energy was -5.49 and Bax-DOXO-CUR binding was -3.83. The most preferable synergistic binding was found with Caspase3 protein, where Caspase3-DOXO docking energy was -1.63 but Caspase3-DOXO-CUR combined docking energy was -3.51. The stability of protein-ligand complexes was accessed with MD simulations and binding free energy calculations, Bcl2-CUR-DOXO combination complex showed ∆G: -25.62, Bax-DOXO-CUR complex showed the maximum ∆G: -34.18, with Caspase-CUR-DOXO complex (∆G: -15.18), indicating the proteins most stable conformation while interacting with CUR + DOXO combination. The correlation between the in vitro and in silico analysis of apoptosis pathway components widens the further research scope for proteomics and organoid studies, which might be worthy for successful clinical trials.

Diet quality and cardiometabolic health in breast cancer survivors: the Pathways Study.

Breast cancer (BC) survivors experience higher rates of cardiometabolic conditions, partly due to treatment. While healthy eating decreases the risk of these conditions in the general population, its association in BC survivors is unclear. We included 3415 participants from the Pathways Study, a prospective cohort of women diagnosed with invasive BC between 2005 and 2013 and followed through 2021. Concordance of food intakes from food frequency questionnaires was estimated for five healthy eating patterns at BC diagnosis: Dietary Approaches to Stop Hypertension (DASH), healthy Plant-based Dietary Index (hPDI), 2020 Healthy Eating Index (HEI), American Cancer Society nutrition guidelines (ACS), and the alternate Mediterranean Diet Index (aMED). Incident hypertension, diabetes, and dyslipidemia were identified through electronic health records. Cumulative incidence rates (CIRs) were estimated accounting for the competing risk of death. Covariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Fine and Gray regression models, stratified by BC treatment status. Over an average 11.5years (range = 0.3-16.3) of follow-up, 554 (16.2%) participants developed hypertension, 362 (10.6%) developed diabetes, and 652 (19.1%) developed dyslipidemia. CIRs for any cardiometabolic condition 15years after BC diagnosis were 39.2% for women in the highest HEI quartile compared to 49.3% in the lowest. After adjustment, women in the highest HEI quartile had lower risks of any cardiometabolic condition (HR = 0.70, 95% CI 0.54-0.91,Ptrend = 0.006), including hypertension (HR = 0.71, 95% CI 0.54-0.94,Ptrend = 0.007), diabetes (HR = 0.57, 95% CI 0.41-0.79,Ptrend < 0.001), and dyslipidemia (HR = 0.77, 95% CI 0.59-0.99,Ptrend = 0.04). Similar associations were observed for DASH, hPDI, and ACS with diabetes incidence. Healthier diets at BC diagnosis, particularly those aligned with the HEI, were associated with lower cardiometabolic risks.

Regulation of the β‑catenin/LEF‑1 pathway by the siRNA knockdown of RUVBL1 expression inhibits breast cancer cell proliferation, migration and invasion.

RUVBL1 is a protein characterized by its DNA‑dependent ATPase activity and DNA deconjugating enzyme function. It is a member of the ATPase (AAA+) protein family associated with various cellular processes. Available research confirms that the expression of RUVBL1 is upregulated in breast cancer (BRCA) cell lines; however, the mechanisms underlying its functional role in BRCA remain unclear. The β‑catenin/lymphoid enhancer factor‑1 (LEF‑1) pathway plays a crucial role in the occurrence and development of BRCA. The aim of the present study was to investigate whether RUVBL1 regulates the proliferation, migration and invasion of BRCA cells by participating in the β‑catenin/LEF‑1 signaling pathway. Reverse transcription‑quantitative PCR (RT‑qPCR) and western blot analysis were employed to compare the RUVBL1 expression levels between normal mammary epithelial cells (MCF‑10a) and BRCA cell lines (MDA‑MB‑231 and MCF‑7). Scratch, Cell Counting Kit‑8 and Transwell assays were utilized to assess the effects of RUVBL1 knockdown on the proliferation, migration and invasion of BRCA cells. Following the downregulation of RUVBL1 expression in vitro, western blot analysis and RT‑qPCR were conducted to investigate its role in regulating the β‑catenin/LEF‑1 pathway. The aforementioned experiments proved that the knockdown of RUVBL1 expression inhibited BRCA cell proliferative, migratory and invasive capabilities, modulating the β‑catenin/LEF‑1 pathway. Collectively, the findings of the present study provide preliminarily confirmation that RUVBL1 participates in the molecular mechanisms of the β‑catenin signaling pathway, which may provide a novel target for BRCA treatment.

The Role of Apparent Diffusion Coefficient (ADC) in Differentiating Between Benign and Malignant Breast Lesions in a Sample of Iranian Women

Background: Breast cancer is the most prevalent cancer among women, emphasizing the need for early detection and accurate diagnosis. This study investigates the role of the Apparent Diffusion Coefficient (ADC) in distinguishing between benign and malignant breast lesions using Magnetic Resonance Imaging (MRI) and Diffusion-Weighted Imaging (DWI). A retrospective cross-sectional study was conducted involving 96 patients with breast lesions who underwent MRI and DWI scans. Methods: Patients were selected from among those who had MRI and DWI scans with b-values of 0, 800, and 1000 s/mm². ADC values were calculated by plotting the Region of Interest (ROI) and extracting corresponding values. Histological evaluations confirmed the diagnosis of the lesions. Statistical analyses included calculating accuracy, sensitivity, and specificity, along with Receiver Operating Characteristic (ROC) curve analysis to determine the optimal cut-off value. Results: The ADC values demonstrated an accuracy of 92.5%, sensitivity of 93.2%, and specificity of 91.2% in differentiating between benign and malignant lesions. The ROC curve analysis established a cut-off value of 1.44 × 10⁻³ mm²/s for effective differentiation. Conclusion: ADC values can serve as a reliable biomarker for distinguishing breast lesions, potentially reducing unnecessary biopsies for benign cases and aiding clinicians in treatment decisions. The integration of ADC measurements into clinical practice could enhance patient management in breast cancer. Further research is warranted to validate these findings and explore additional markers to improve diagnostic accuracy in breast cancer management.

Harnessing the Power of Alkaloids in Breast Cancer Treatment: A Review of Therapeutic Efficacy and Challenges

Harnessing the Power of Alkaloids in Breast Cancer Treatment: A Review of Therapeutic Efficacy and Challenges

NELBI score: a new clinical calculator of thirty-day mortality following systemic anticancer therapy in breast cancer patients near the end of life.

Appropriately timed cessation of systemic anticancer treatments is an important part of a patient's quality of life (QoL). We aimed to determine the right time to discontinue systemic anticancer therapy (SACT) and switch to the best supportive care for patients with advanced breast cancer (BC) who are nearing the end of life. We identified 200 BC patients who died within 30days after palliative SACT. Laboratory parameters and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were recorded when the patients received their last SACT and at the time of their penultimate treatment. The (Neutrophil-ECOG-LDH-Bilirubin) 'NELBI' score, created on the basis of the optimum cut-off points of ECOG PS, neutrophil count, bilirubin level, and lactate dehydrogenase (LDH) level, which can predict mortality within 30days after SACT, was scored between 0 and 4. Patients were stratified on the basis of the NELBI score. A total of 4164 patients receiving palliative treatment for advanced BC were examined. A total of 4.8% of patients died within 30days after SACT. The percentage of patients who died within 30days after SACT among all deceased patients was 19.4%. The median time from the last systemic treatment to death was 19.5 ± 7.85 (95% CI 18.06-20.26) days, and the median time from the penultimate treatment to death was 43.0 ± 24.65 (95% CI 46.81-53.85) days. A total of 21.3%, 58.0%, 70.7%, and 88.9% of patients with NELBI scores of 0, 1, 2, and 3-4, respectively, died within 30days after SACT. Compared with a NELBI score of 0, a NELBI score of 1 (OR = 5.095; 95% CI 2.654- 9.784; p < 0.001), a NELBI score of 2 (OR = 8.911; 95% CI 4.299-18.474; p < 0.001), and a NELBI score of 3-4 (OR = 29.500; 95% CI 6.135- 141.847; p < 0.001) was associated with significantly greater 30-day mortality. The AUC of the NELBI scoring for 30-day mortality prediction after SACT was 0.713. The 'NELBI' scoring system has the potential to significantly improve patient care by guiding the appropriate discontinuation of SACTs in patients with BC.

Radiation therapy and immigration status in women with breast cancer.

Radiation therapy (RT) is an essential component of treatment for breast cancer (BC), and while indications and delivery techniques evolve, inequities in access remain. Immigrant women face barriers navigating the healthcare system, but impact of immigration status on delivery of adjuvant RT for BC has not been studied. A population-level study using provincial databases was conducted including women with Stage I-III breast cancer diagnosed between 2010-2016 in Ontario, Canada undergoing breast conserving surgery (BCS). Co-variates including age, co-morbidity, socioeconomic factors, stage, receptor status and treatment facility factors were collected. Primary outcome was the proportion of women undergoing RT and secondary outcome was time from surgery to RT. Of 30,712 women, 4,293 (14 %) were immigrants. Immigrants were younger (54.6 vs. 62.5 years) and less often had Stage I (49.4 % vs. 57.0 %) disease. Odds of receiving RT after BCS was 0.81 (95 %CI 0.74-0.89p < 0.0001) for immigrant vs. non-immigrant women. When stratified by age, immigrant women < 70 were less likely to receive RT when compared to non-immigrants, while no differences were observed for those ≥ 70. There was a small, though significant difference in mean wait-time from surgery to RT in patients who did not receive chemotherapy [immigrant vs non-immigrant 72.7 days (28.8 SD) vs. 77.7 days (31.0 SD), p < 0.0001]. Our study demonstrates a lower proportion of immigrant women receiving RT after BCS compared to non-immigrant women. There was a small difference in wait-time to radiation. Further research is needed to explore system, provider, and patient factors driving this difference.