Treatment Of Breast Cancer Research Articles

Long-Term Results of Intensity Modulated Radiotherapy (IMRT) with Helical Tomotherapy in Non-Metastatic Breast Cancer Patients: Final Analysis

Background: Intensity modulated radiotherapy with helical tomotherapy (IMRT-HT) is used in the breast cancer (BC) treatment for years now to obtain homogeneous dose distribution in the treated volumes and reduce the doses to organs at risk. The purpose of this study was to evaluate our experience in terms of local control, overall survival, progression free survival and adverse events in BC patients treated with IMRT-HT with long term follow-up. Methods: This study is a retrospective data analysis of patients irradiated with IMRT-HT. Overall survival (OS) and progression free survival (PFS) curves were plotted with Kaplan-Meier method. We also analyzed the OS and PFS data by molecular subgroups of the population. Long-term toxicities including skin, cardiac and pulmonary complications were also evaluated. Multivariant logistic regression analysis was performed to determine the independent predictors of the side effects. Results: Between 2009 and 2015, a total of 194 breasts in 179 women with nonmetastatic breast cancer were treated. Most of the tumors were grade III and N+. With a median follow-up of 10 years, we observed 9 local recurrences, 2 loco-regional recurrences, and 29 patients experienced metastatic disease. Only 18 patients are dear, of them 7 cases with breast cancer death. At 10 years, the Local recurrence free survival was 95.3% [95%CI: 92.1–98.5], the loco-regional relapse free survival was 94.5% [91.1–98.1]. The metastases free survival was 82.9% [76.9–89.3]. The progression free survival was 79.9 [73.6–86.7]. The cancer specific survival was 94.3%, and the overall survival 88% [82.8–93.5]. At long term, there were no cardiac, lung, thyroid, digestive radio induced toxicities. A small number of patients experienced grade I or II fibrosis. Conclusions: IMRT-HT could be safely used for adjuvant breast cancer irradiation in patients with complex anatomy. IMRT-HT provides favourable long-term prognosis, while late toxicity is acceptable.

Cyclin-dependent kinase 4/6 inhibitor resistance mechanisms and strategies for subsequent treatment in breast cancer: A comprehensive review

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have transformed the therapeutic landscape for hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer, demonstrating significant efficacy in both early and advanced stages of the disease. Combined with endocrine therapy, these inhibitors have dramatically improved survival outcomes. However, resistance to CDK4/6 inhibitors inevitably develops, posing a significant challenge in clinical management. Resistance to CDK4/6 inhibitors can develop through inherent and acquired fashions, and their mechanisms are explored in this comprehensive review. Inherent resistance arises from pre-existing genetic or signaling pathway alterations that diminish cancer cell sensitivity to CDK4/6 inhibitors. Acquired resistance, on the other hand, develops over time through mechanisms, such as the activation of alternative signaling pathways or changes in the tumor microenvironment. The review also examines potential biomarkers for predicting resistance, especially circulating tumor DNA markers, and discusses strategies to overcome resistance. These include combination therapies targeting multiple pathways simultaneously, sequential approaches to delay the onset of resistance, and the development of next-generation CDK4/6 inhibitors with improved efficacy and reduced resistance potential. Understanding resistance mechanisms and developing effective countermeasures are crucial for optimizing patient outcomes and extending the clinical benefits of CDK4/6 inhibitors in cancer therapy. Leveraging these insights will enable clinicians to personalize treatment strategies, ultimately enhancing the long-term effectiveness of CDK4/6 inhibitors in managing breast cancer.

Endothelial cell pY397-FAK expression predicts risk of breast cancer recurrences after radiotherapy in SweBCG91-RT cohort.

Identifying biomarkers of radiotherapy (RT) response is important for optimising the treatment of early breast cancer (BC). Here we tested the interaction between endothelial cell (EC) expression of phospho-Tyr397-FAK (pY397-FAK) and adjuvant-RT on clinical outcomes after breast-conserving surgery (BCS) within a randomised study. Preclinical data suggests an enhanced effect of RT with low EC_ pY397-FAK expression. We analysed tissue microarrays (TMAs) from the SweBCG91-RT (stage I-II, lymph node-negative) BC cohort, consisting of 1,178 patients randomly assigned to receive either BCS alone or BCS plus adjuvant-RT. TMA sections were immunostained for pY397-FAK, CD31, α-smooth-muscle-actin (αSMA) and pan-cytokeratin (panCK). HALO analysis scored mean pY397-FAK intensity in CD31+ ECs, panCK+ tumour epithelial cells (TCs) and αSMA+ mural/stromal cells per core. For 822 patients, multivariable Cox regression analysis was performed for the primary and secondary 5-year endpoints, locoregional recurrence (LRR) and 'all recurrence', respectively, as dependent variables, and RT and EC_pY397-FAK as independent variables. EC_ pY397-FAK expression was not predictive for the primary endpoint, LRR (p=0.098), but the direction of the RT effect was in line with preclinical findings. For the secondary endpoint, all recurrence, there was a significant interaction (p=0.026) between EC_ pY397-FAK and RT. Without RT, higher EC_ pY397-FAK expression resulted in lower risk for all recurrence (HR 0.74 per SD, CI 95% 0.57-0.96, p=0.026). Within the first 5-years post-BCS, patients with low EC_pY397-FAK expression derive greater benefit from RT than patients with high EC_pY397-FAK expression. However, without RT low EC_pY397-FAK expression is associated with a higher risk of recurrence.

Reactive Oxygen Species Inducing Triazolylpyridine-Based Ru(II)/Ir(III) Complexes for Therapeutically Enhanced Triple-Negative Breast Cancer Treatment.

The effectiveness of existing systemic and targeted therapies remains limited in triple-negative breast cancer (TNBC) treatment. Much research has been conducted on reactive oxygen species (ROS)-mediated cancer cell death to overcome the shortcomings of the currently applied chemotherapeutic treatments. Herein, we have developed novel Ru(II)/Ir(III)-mediated triazolylpyridine complexes as ROS inducers. Upon entering the TNBC cells, the Ru(II) complex effectively accumulated in mitochondria and triggered the creation of ROS, facilitating dysfunction of mitochondria and oxidative DNA damage, ultimately causing death of cells through G2/M phase cell cycle arrest. Eventually, this complex induced the upregulation of BAX (pro-apoptotic protein) and downregulation of BCL-2 (antiapoptotic protein) and triggered the caspase 3/9 pathway and released cytochrome c in the cytosol for apoptosis. The complex JRu (RuII triazolylpyridine) significantly reduced the integrity and viability of TNBC 3D spheroids.

Perceived barriers to reaching equity in effective access to diagnosis and treatment for women with breast cancer in Chile

Globally, it has been reported inequities in breast cancer effective access to health care. The objective of this study was to explore perceived inequities in access to effective diagnosis and treatment in women with breast cancer according to Tanahashi model and social determinants of health model. An exploratory case study, under a qualitative paradigm, was conducted. Theoretical sampling guided the selection of diverse participant profiles, comprising breast cancer patients, healthcare professionals and a civil society leader. The strategies for the recruitment process included social networks, civil society organizations, health professionals, and the snowball technique. Online semi-structured interviews were conducted. Interviews were transcribed, anonymized, and coded using ATLAS.Ti for deductive thematic analysis. Barriers to effective healthcare access were identified in all components of Tanahashi model. Accessibility and acceptability were the components with most perceived barriers. From the determinants of health model, a woman from the public health system, with low income, under 30 or over 40, and residing in a different region from the metropolitan region faces more barriers to access to an effective healthcare. The main barriers were for the high centralisation of healthcare in Chile, not integrated health system network, misinformation to the patient, and non-humanized healthcare. The results of this study offer a comprehensive exploration of perceived barriers to effective breast cancer diagnosis and treatment in Chile, using a qualitative approach incorporating diverse perspectives. Findings underscore significant systemic challenges across Tanahashi’s model components, impacting the overall care experience. The study reveals structural inequities hindering healthcare access, reflecting global patterns in fragmented health systems.

Breast Cancer Risk and Management in the Endocrine Clinic: A Comprehensive Review.

This review seeks to provide endocrine clinicians with a comprehensive analysis of breast cancer risk, diagnostic modalities and management strategies in women with endocrine disorders, with particular emphasis on the influence of metabolic factors such as diabetes and obesity, and the role of Menopausal Hormone Therapy (MHT). The review examines a spectrum of endocrine disorders commonly encountered in clinical practice, including Multiple Endocrine Neoplasia Types 1 (MEN1), 2 (MEN2) and 4 (MEN4), Von Hippel-Lindau syndrome (VHL), Pheochromocytoma and Paraganglioma (PPGL), Acromegaly, Hyperprolactinaemia, Polycystic Ovary Syndrome (PCOS), Congenital Adrenal Hyperplasia (CAH), Turner Syndrome, alongside metabolic conditions such as diabetes and obesity and the effects of MHT. The review critically appraises each disorder's association with breast cancer risk, screening implications and therapeutic management. This analysis focuses on women with the aforementioned endocrine and metabolic disorders, assessing their specific breast cancer risk profiles, informed by the latest clinical evidence and molecular insights. The review comprehensively evaluates current evidence-based approaches to screening, diagnostic accuracy and treatment in this patient cohort. Emphasis is placed on the metabolic derangements, hormonal influences and genetic predispositions that modulate breast cancer risk, providing disorder-specific recommendations for individualised care. The findings indicate a significantly elevated breast cancer risk in patients with MEN1, necessitating early initiation of MRI screening by age 40. In MEN2, emerging evidence suggests that combining RET inhibitors with endocrine therapy may yield clinical benefits, although further research is needed to validate this approach. The breast cancer risk associated with MEN4 and VHL syndromes, while documented, remains less well-characterised, requiring further investigation. Diabetes and obesity are confirmed as major modifiable risk factors, particularly in postmenopausal women, where hyperinsulinemia and metabolic dysfunction contribute to increased incidence and poorer outcomes, notably in triple-negative breast cancer (TNBC). The role of MHT, particularly combined oestrogen-progestogen therapy, is strongly associated with increased breast cancer risk, particularly for hormone receptor-positive malignancies, necessitating cautious use and personalised treatment planning. In contrast, oestrogen-only MHT appears to confer a reduced risk in women post-hysterectomy. For patients with PCOS, CAH and Turner Syndrome, while definitive evidence of elevated breast cancer risk is lacking, individualised screening strategies and careful hormone therapy management remain essential due to the complex interplay of hormonal and metabolic factors. The review highlights the need for personalised breast cancer screening and management protocols in women with endocrine and metabolic disorders. For high-risk groups such as MEN1 patients, early initiation of MRI screening is warranted. In women with diabetes and obesity, targeted interventions addressing hyperinsulinemia and metabolic dysfunction are critical to mitigating their increased cancer risk. The association between MHT and breast cancer underscores the importance of individualised risk stratification in hormone therapy administration, particularly in women with predisposing genetic or endocrine conditions. Enhanced surveillance tailored to the unique risk profiles of endocrine disorder patients will facilitate early detection and improve clinical outcomes. However, further large-scale studies are necessary to refine these associations and develop robust, evidence-based guidelines.

Molecular Insights into Breast Cancer Treatment: An Integrated Approach of Network Pharmacology and Component Analysis for Lansium parasiticum Bark Extract

Medicinal plants containing multi-components have the potential for multi-target genes, multi-pathways, and various effects on diverse diseases. With the increasing technological advancements, understanding the complex interactions between multi-component substances and biological systems is becoming more crucial. In this context, conventional experimental research might have limitations as it typically focuses on the impact of one component on one gene. The objective of this research is to identify compounds in the bark extract of Lansium parasiticum and elucidate the molecular mechanisms of these compounds in inhibiting the progression of breast cancer cells using a network pharmacology approach. Compound identification in Lansium parasiticum bark extract (LPBE) has been conducted using Liquid Chromatography Tandem Mass Spectrophotometry (LC-MS/MS) technique. ADMET predictions were utilized to determine the absorption and bioavailability profiles. A network pharmacology approach employing Cytoscape 3.9.1, GeneCards, Disgenet, STRING 2.0.0, SRplot, and Kyoto Encyclopedia of Genes and Genomes (KEGG) was used to predict the anti-cancer molecular mechanisms of these compounds. Seventeen active compounds have been successfully identified via LC-MS/MS. Among these, the compounds Moronic Acid, 4-Morpholineacetic Acid, and Ursolic Aldehyde were found in the highest concentrations. The results of the network pharmacology analysis indicate that the compounds in LPBE are involved in three potential pathways for breast cancer treatment: the NF-κß signaling pathway (hsa 04064), microRNA in cancer (hsa05206), and apoptosis (hsa04210). Target genes implicated in these pathways include BAX, BCL2, TNF-α, PARP1, STAT3, NOTCH1, and NF-κß1. It can be concluded that LPBE contains compounds with potential for treating breast cancer, as they are predicted to interact with relevant target pathways and genes. Therefore, further research is highly recommended, particularly in the development of drugs for breast cancer.Keywords: apoptosis, microRNA, NF-κß, TNF-α, STAT3.

Research trends on lymphedema after mastectomy for breast cancer patients from 2000 to 2023: a scientometric analysis

BackgroundBreast cancer-related lymphedema (BCRL) is a common and debilitating complication following breast cancer treatment. Despite its significant impact on patients’ quality of life, bibliometric analyses focusing on BCRL are scarce. This study aims to explore global research trends on BCRL from 2000 to 2023, identify existing knowledge gaps, and highlight emerging focus areas through a bibliometric approach.MethodsA comprehensive search was conducted using the Web of Science (WOS) database to retrieve literature published between January 2000 and November 2023. Bibliometric analyses and visualizations were performed using R Studio, CiteSpace, and VOSviewer. Key data extracted included publication trends, contributing countries and institutions, leading authors, journals, research categories, and keywords. Outcome measures for analysis included the number of publications, citation counts, author productivity, and keyword co-occurrence.ResultsA total of 919 eligible publications from 52 countries and regions, 1,163 institutions, and 3,550 authors were identified. These publications appeared in 255 journals, with “Lymphology” emerging as the journal with the highest citation count. The USA was the most prolific contributor to the field. The annual number of publications demonstrated a consistent upward trend. Keyword co-occurrence analysis revealed prominent research hotspots, including “lymphedema,” “women,” “breast cancer,” “arm lymphedema,” and “quality of life.” Emerging keyword trends from 2021 to 2023 highlighted “prevention” and “validity” as pivotal research frontiers.ConclusionsThis bibliometric study highlights the growing interest in breast cancer-related lymphedema research and identifies key areas for future investigation, including prevention, diagnosis, and treatment strategies. The results underscore the need for further exploration of these emerging research areas to improve patient outcomes.

Quantifying the tumour vasculature environment from CD-31 immunohistochemistry images of breast cancer using deep learning based semantic segmentation

BackgroundTumour vascular density assessed from CD-31 immunohistochemistry (IHC) images has previously been shown to have prognostic value in breast cancer. Current methods to measure vascular density, however, are time-consuming, suffer from high inter-observer variability and are limited in describing the complex tumour vasculature morphometry.MethodsWe propose a method for automatically measuring a range of vascular parameters from CD-31 IHC images, which together provide a detailed description of the vasculature morphology. We first used a U-Net based convolutional neural network, trained and validated using 36 partially annotated whole slide images from 27 patients, to segment vessel structures and tumour regions from which the measurements are taken. The model also segments the vascular smooth muscle, benign epithelium, adipose tissue, stroma, lymphocyte clusters, nerves and CD-31 positive leukocytes, and we applied it to an additional 21 images from 15 patients. Using these segmentations, we investigated the relationship between the various tissue types and the vasculature and studied the relationship of various vascular parameters with clinical parameters. We also performed a 3D histology analysis on a separate tumour sample as a proof of principle, providing a more comprehensive visualization of vasculature morphology compared to the standard 2D cross-section of a tissue sample.ResultsUsing two-way cross-validation, we show that vessels were accurately segmented, with Dice scores of 0.875 and 0.856, and were accurately identified, with F1 scores of 0.777 and 0.748. All vascular parameters exhibit strong (r>0.70.7$$\\end{document}]]>) and significant (p<0.001) correlations with measurements taken from the manual ground truth vessel segmentations. A significant relationship between the major/minor axis ratio, a measure of elongation, and the tumour grade was found.ConclusionOur proposed method shows promise as a tool for studying the tumour vasculature and its relationship with surrounding cells and tissue types. Furthermore, the correlation with tumour grade highlights the clinical relevance of our approach. These findings suggest that our method could have substantial implications for improving prognostic assessments and personalizing therapeutic strategies in breast cancer treatment.

Meta-analysis of the association between overexpression of RAD51 family genes and prognosis and clinical features in breast cancer.

The RAD51 family of genes play a crucial role in the repair of DNA damage, and increasing evidence suggests a close link between the aberrant expression of RAD51 family genes and the development of breast cancer. However, their prognostic and clinical relevance remains subjects of ongoing debate. This study aims to systematically investigate the relationship between the overexpression of RAD51 family genes and breast cancer prognosis, as well as their association with clinicopathological characteristics, through a comprehensive meta-analysis. PubMed, EMBASE, OVID, Web of Science, Scopus, and Cochrane Library were systematically searched for relevant studies published up to August 25, 2024. Two independent researchers screened the literature according to predefined inclusion and exclusion criteria and extracted relevant data. Statistical analyses were conducted using the Meta package in R 4.2.2. Thirteen studies comprising 20,222 breast cancer patients were included. High expression of RAD51 family genes was associated with poorer overall survival (OS) [HR = 1.305, 95%CI (1.145-1.488), P < 0.01], disease-free survival/distant metastasis-free survival (DFS/DMFS) [HR = 1.588, 95%CI (1.208-2.089), P < 0.01], and disease-specific survival (DSS) [HR = 1.403, 95%CI (1.066-1.846), P = 0.02]. In addition, subgroup analyses further showed that high RAD51 expression was associated with worsened OS [HR = 1.475, 95%CI (1.275-1.706), P < 0.01], DFS [HR = 1.584, 95%CI (1.133-2.215), P < 0.01] and progression-free survival (PFS) [HR = 2.439, 95%CI (1.172-5.075), P = 0.02]. In contrast, high expression of RAD51 paralogs was linked to improved PFS prognosis [HR = 0.870, 95%CI (0.797-0.949), P < 0.01]. Regarding clinical characteristics, high expression of RAD51 family genes was significantly associated with human epidermal growth factor receptor 2 (HER2) positivity [OR = 1.782, 95%CI (1.328-2.392), P < 0.01]. The overexpression of RAD51 family genes is correlated with unfavorable prognosis in breast cancer and exhibits a strong association with HER2-positive subtypes. These findings underscore the potential of RAD51 family genes as prognostic biomarker and therapeutic targets in breast cancer management.

PEGylated Nanoliposomes Encapsulated with Anticancer Drugs for Breast and Prostate Cancer Therapy: An Update

There are different types of cancer treatments, including surgery, radiotherapy, and chemotherapy. However, the complexity of cancer has resulted in treatment challenges to medicinal scientists and a socio-economic burden to the public health system globally. The pharmacological limitations associated with the current conventional anticancer drugs include lack of specificity, poor bioavailability, toxicity, drug resistance, and poor delivery mechanisms, which make cancer treatment challenging. Thus, the number of cancer cases is escalating rapidly, especially breast and prostate cancer in women and men, respectively. The application of nanoformulations is gaining momentum for treating different cancer types. However, they also exhibit challenges that must be addressed for effective cancer treatment. Nanoliposomes are nanoformulations that are widely explored for cancer treatment with interesting therapeutic outcomes. They have been functionalized with PEG to further improve their therapeutic outcomes. Hence, this review provides an update on PEGylated nanoliposomes loaded with anticancer drugs for the treatment of breast and prostate cancer, focusing on pre-clinical studies published in the last decade (2015 to 2024) to reflect the recent advancements made in the design of PEGylation nanoliposomes. Highlights of the clinically and commercially available PEGylation nanoliposomes are also presented in this review.

Exosome Platform with Three-in-One Functionality of mRNA Therapy, Immune Checkpoint Blockade, and Mild Photothermal Therapy for the Treatment of Triple-Negative Breast Cancer.

Immune checkpoint blockade (ICB) has shown promising potential for treating triple-negative breast cancer (TNBC), but its efficacy is limited, mainly due to the "cold," suppressive immune tumor microenvironment (TME). Therefore, improving the TME is crucial for enhancing therapeutic effects against TNBC. Here, we presented a multifunctional nanotherapeutic platform (ALEvs@LNPs) designed to combine cytokine-sensitized mild photothermal therapy, ICB, and interleukin-2 (IL2) mRNA therapy to reprogram the TME, thereby improving the efficacy of ICB therapy in TNBC. Tumor cell-derived exosome-camouflaged lipid nanoparticles with antilymphocyte activation gene-3 (LAG3) were developed to codeliver the photothermal agent IR806, IL2 mRNA, and LAG3 inhibitory antibody (anti-LAG3). Mild photothermal therapy facilitated the reprogramming of "cold" tumors into "hot," thereby enhancing the therapeutic effects of ICB. Meanwhile, ICB also promoted cytokine secretion, increasing the sensitivity of tumor cells to heat. Additionally, IL2 mRNA therapy induced T-cell proliferation and activation, further augmenting the efficacy of ICB. Together, these three therapies established a positive feedback loop that enhanced the therapeutic effects of ICB. This multifunctional nanotherapeutic platform effectively reprogrammed the "cold," suppressive immune TME, offering a promising strategy for TNBC treatment.

Treatment and reasons for choosing treatment in breast cancer patients who underwent next-generation sequencing test.

Next-generation sequencing (NGS) is commonly used in clinical practice to decide treatment based on genomic information. This study was performed to optimize the proportion of actionable gene profiling and treatment based on genetic alterations in breast cancer at one of cancer centers in Japan. Patients with breast cancer who reported NGS results at one of cancer centers in Japan from August 2019 to December 2023 were retrospectively investigated by reviewing their electronic medical records. Patients were examined using the OncoGuideTM NCC Oncopanel System, FoundationOne® CDx, or FoundationOne® Liquid CDx. The evidence levels for drug recommendation were added for each gene alteration according to the guidelines from three Japanese oncology-related societies. ''Actionable alterations'' were those at evidence levels A-D, including high microsatellite instability and high tumor mutation burden status. "Patients with recommended drug" (approved, investigational, and off-label drugs) were defined as those who were selected by the Molecular Tumor Board. Of the 106 patients, 54 were tested using the NCC Oncopanel System and 50 using FoundationOne CDx. The most frequent alterations were TP53 mutations (52.8%) and PIK3CA mutations (31.1%). Of the 56 patients (52.8%) with recommended drugs, 11 (10.4%) received genome-matched therapy and only three (2.8%) participated in clinical trials. The most common reason for not receiving genome-matched therapy was patient refusal for personal reasons, although clinical trials were available (18 patients). The top reasons for patients not receiving the recommended genome-matched therapy were factors related to the patient, including a number of prior treatments higher than what was allowed by the eligibility criteria of the clinical trials, and poor physical condition. Most patients received four or more regimens of cytotoxic chemotherapy before NGS. NGS is only available at the late phase of treatment in Japan, which would constitute a problem for the treatment of breast cancer.

Impact of Breast Cancer Systemic Therapies on Fertility

Abstract Purpose of Review This review examines the impact of breast cancer treatments on fertility in young women and explores strategies for fertility preservation. It highlights what is known about the effects of chemotherapy, hormonal therapies, and targeted treatments for breast cancer on ovarian function, emphasizing the importance of integrating fertility preservation into oncology care. Recent Findings Systemic treatments, including chemotherapy and targeted agents like PARP inhibitors and CDK4/6 inhibitors, have the potential to significantly affect ovarian reserve and fertility. As treatment protocols become more prolonged, patients may consider treatment interruption to attempt pregnancy, and studies such as the POSITIVE trial offer new insights into the safety of pregnancy after breast cancer. Summary Personalized fertility preservation strategies are essential for optimizing outcomes in young breast cancer patients. Ongoing research to better understand the effects of treatment on future fertility, as well as mitigation strategies, is necessary to support informed decision-making and improve quality of life.

Prediction of Secondary Metabolite Compounds in Lotus (Nelumbo nucifera Gaertn.) Targeting Androgen-α Receptors for Breast Cancer Treatment Using Molecular Docking

Breast cancer (BC) is a malignant tumor that grows in the breast tissue and can spread to other organs. BC is often found at an advanced stage and therefore has a poor prognosis. With 68,858 cases, BC is the most common type of cancer in Indonesia. The development of breast carcinoma is strongly influenced by steroid hormones and their receptors, such as estrogen, progesterone, and androgen. Androgen receptors (AR) are found more (70-90%) compared to estrogen receptors (60-80%) and progesterone receptors (50-70%). Therefore, research on natural compounds that inhibit cancer cell proliferation influenced by AR needs to be increased. The lotus plant (Nelumbo nucifera Gaertn.) has been used as a traditional herbal medicine and food in Asia. Bioactive compounds in lotus have therapeutic potential against BC. In the pharmacophore screening results, five hit compounds were found: isorhamnetin, luteolin, catechin, kaempferol, and apigenin. The compound with the best pharmacophore fit score value is isorhamnetin with a value of 41.31, while the compound with the best binding affinity to AR is kaempferol with a binding affinity of -9.44 and an inhibitor constant of 121.12 nM.Keywords: breast-cancer, androgen-α receptor, lotus, molecular docking.

Identifying Core Self-reported Adverse Events Associated With Chemotherapy Among Patients With Breast Cancer: A Network Analysis.

Women in treatment for breast cancer and undergoing chemotherapy often experience multiple chemotherapy-related adverse events simultaneously, making it essential for healthcare providers to pinpoint the core adverse event that can be targeted for more precise interventions. To identify the core chemotherapy-related adverse events using network analysis in Chinese patients with breast cancer. Data were collected from September 1, 2022, to November 30, 2022. Network analysis was used to construct an adverse events network. Node centrality was assessed using strength, closeness, and betweenness centralities. Comparisons of networks by different chemotherapy cycles were also made. A total of 195 patients were eligible for data analysis. In the overall network, fatigue (rS = 7.0612, rC = 0.0136, rB = 76) was the most central adverse event, followed by decreased appetite (rS = 6.8378, rC = 0.0124, rB = 42). In the comparison of networks by different chemotherapy cycles, muscle pain was the most central adverse event in the early phase of chemotherapy; fatigue was the most central adverse event in the middle phase of chemotherapy and remained the most central adverse event in the late phase of chemotherapy. This study confirmed the core roles of fatigue and decreased appetite in chemotherapy-related adverse events in patients with breast cancer from patient-reported outcomes. Healthcare providers should focus their interventions on core adverse events to improve the efficiency of managing adverse events in patients with breast cancer undergoing chemotherapy.

Enhancing breast cancer prediction through stacking ensemble and deep learning integration

Breast cancer is one of the most common types of cancer in women and is recognized as a serious global public health issue. The increasing incidence of breast cancer emphasizes the importance of early detection, which enhances the effectiveness of treatment processes. In addressing this challenge, the importance of machine learning and deep learning technologies is increasingly recognized. The aim of this study is to evaluate the integration of ensemble models and deep learning models using stacking ensemble techniques on the Breast Cancer Wisconsin (Diagnostic) dataset and to enhance breast cancer diagnosis through this methodology. To achieve this, the efficacy of ensemble methods such as Random Forest, XGBoost, LightGBM, ExtraTrees, HistGradientBoosting, AdaBoost, GradientBoosting, and CatBoost in modeling breast cancer diagnosis was comprehensively evaluated. In addition to ensemble methods, deep learning models including convolutional neural network (CNN), recurrent neural network (RNN), gated recurrent unit (GRU), bidirectional long short-term memory (BILSTM), long short-term memory (LSTM) were analyzed as meta predictors. Among these models, CNN stood out for its high accuracy and rapid training time, making it an ideal choice for real-time diagnostic applications. Finally, the study demonstrated how breast cancer prediction was enhanced by integrating a set of base predictors, such as LightGBM, ExtraTrees, and CatBoost, with a deep learning-based meta-predictor, such as CNN, using stacking ensemble methodology. This stacking integration model offers significant potential for healthcare decision support systems with high accuracy, F1 score, and receiver operating characteristic area under the curve (ROC AUC), along with reduced training times. The results from this research offer important insights for enhancing decision-making strategies in the diagnosis and management of breast cancer.

Efficacy and safety of mirogabalin therapy for paclitaxel-induced peripheral neuropathy (MICHEL Study): A pilot study

Introduction Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent adverse event without an established, standard treatment. As mirogabalin is a gabapentinoid confirmed useful for diabetic, peripheral neuropathic pain, we examined the efficacy of mirogabalin for CIPN using quantitative sensory and pain analytical devices. Methods This was a single-arm, open-label, prospective study conducted at the University of Tsukuba Hospital between April 2022 to April 2024. Patients with grade 2 or higher CIPN during weekly paclitaxel treatment for primary breast cancer were enrolled and received mirogabalin orally for 4 weeks. The primary endpoint was the Visual Analogue Scale (VAS) for peripheral neuropathy. Patient Neurotoxicity Questionnaire (PNQ) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) scores were obtained and PainVision was used as an objective CIPN evaluation. Results A total of 20 patients were enrolled. The median VAS score before starting mirogabalin was 13.50 for the hands and 25.00 for the feet. After 4 weeks of treatment, there was significant worsening in the hands (VAS score of 37.00) but no significant difference was observed for the feet. There were no significant differences in PNQ of the limbs between before and 4 weeks after the mirogabalin treatment, although the mean of the NEUROTOXICITY SUBSCALE of FACT/GOG-NTX significantly worsened. Median PainVision scores for feet also significantly worsened from 50.30 to 89.40, but no significant change was observed for hands. PainVision feet score changes negatively correlated with FACT/GOG-NTX total scores. In the patient satisfaction survey, 14 patients (70%) were satisfied with mirogabalin and 15 patients (75%) wanted to continue. Conclusions Although mirogabalin was not wholly effective for CIPN caused by paclitaxel treatment in breast cancer patients, the satisfaction survey suggests some patient-perceived benefits which cannot be detected by conventional evaluation methods.

An initial benchmark of the quality of the diagnosis and surgical treatment of breast cancer in South Africa

Background. Monitoring quality indicators to improve breast cancer care is well established in high-income countries. This is the first evaluation of diagnostic and surgical quality indicators for initial benchmarking of breast cancer care in South Africa (SA). Objective. To measure the adherence rates to quality indicators among women with breast cancer in SA. Methods. Ten quality indicators were evaluated for 3 545 breast cancer patients across four SA surgical breast units using a shared electronic patient record system. Data quality and adherence rates with differences between units were determined. The effect of HIV status on adherence was assessed by multivariate Poisson regression analyses. Results. Our electronic patient record reliably measured most quality indicators. Rates of positive margins (5.7%), overall axillary surgery (95.8%) and appropriate treatment sequencing in locally advanced breast cancer patients (98.4%) consistently reached minimum international standards. Rates of multidisciplinary team discussion (72.2%), radiotherapy (66.7%) and sentinel node biopsy (39.6%) showed wide cross-site variance. Histopathology reporting (62.0%), breast-conserving surgery (19.4%) and number of nodes excised with axillary dissection (47.3%) and sentinel node biopsy (82.7%) were consistently below minimum standards. Unit volumes were achieved consistently in Gauteng Province, but only for some years in KwaZulu-Natal Province; surgeon volumes were achieved across all units. HIV status did not affect adherence levels. Most quality indicators were well measurable, but data quality on reoperations and surgeon volumes was poor. Conclusion. We evaluated local quality indicators for an initial benchmark, and the most emergent gaps in care are the receipt of radiotherapy and underutilisation of sentinel node biopsy.

Protective Factors Associated with Normal Lymphatic Function After Axillary Lymph Node Dissection for Breast Cancer Treatment.

Risk factors associated with developing lymphedema following axillary lymph node dissection (ALND) are well-described in the literature. However, lymphedema diagnosis criteria is arbitrary and can vary between studies. This study instead aims to identify protective factors associated with normal lymphatic function after ALND for treatment of breast cancer. This was a prospective study of women treated with unilateral ALND for breast cancer between 2020 and 2023. Patients with normal lymphatic function were defined as meeting all of four criteria: <10% arm volume change from baseline, <10 bioimpedance change from baseline, no compression use, and Stage 0 on ICG lymphography at one year follow-up. All other patients were classified as having abnormal lymphatic function. Univariable and multivariable logistic regression were used to examine variables possibly associated with normal lymphatic function. Of 150 patients with 1-year follow-up, 39 patients (26%) had normal lymphatic function and 111 patients (74%) had abnormal lymphatic function. On multivariable analysis, immediate lymphatic reconstruction (ILR) and younger age were significantly associated with normal lymphatic function. The odds of normal lymphatic function in patients who had ILR were 2.79 times higher than that of patients who did not undergo ILR (odds ratio [OR] = 2.79, 95% confidence interval [CI] = 1.23-6.69, p = 0.017). Meanwhile, increased age was associated with decreased odds of normal lymphatic function (OR = 0.93, 95% CI = 0.89-0.97, p = 0.001). Immediate lymphatic reconstruction and younger age are significantly associated with normal lymphatic function 1 year after ALND. These findings suggest that undergoing ILR may be protective against developing breast cancer-related lymphedema.