SACM - United Kingdom
Permanent URI for this collectionhttps://drepo.sdl.edu.sa/handle/20.500.14154/9667
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Item Restricted The Supportive Care of Saudi Women with Breast Cancer(Saudi digital library, 2025) Alkhyat, Alhanouf; Topping, Anne; Hallett, NutmegSupportive Care Needs of Saudi Women with Breast Cancer: A Mixed Methods Convergent Design Study Women with breast cancer can experience a range of informational, psychological, and physical supportive care needs at different stages of the cancer journey. There is limited insight and understanding of the breast cancer experience and supportive care needs from the perspective of the Middle East and North Africa (MENA), region and specifically Saudi Arabian women. Further, it is less clear which needs are most pressing to women, and at what point in the care pathway these needs arise. In this study, I aimed to fill that gap by exploring the supportive care needs of women in Saudi Arabia and evaluating the applicability of a supportive care framework to determine its relevance to the care of women with breast cancer in Saudi Arabia and more broadly the MENA region. Methods: A mixed methods exploratory convergent design was used. Cross-sectional surveys were applied, including the Supportive Care Needs Survey short form 34 (SCNS-SF34 – Arabic version), with eight supplementary questions that were specific to breast cancer patients, plus 15 additional items derived from the MENA region scoping review conducted by the researcher. All items were mapped against the identified supportive care needs framework and modified based on the scoping review findings. Then, the instruments were piloted to assess face validity and subsequently administered to Saudi women with breast cancer (n=85) recruited from one specialist cancer centre. Descriptive statistics were used, followed by Rasch modelling to estimate reliability, validity and dimensionality. Semi-structured interviews with a maximum variation sub- sample of Saudi women (n=20) were analysed using the framework method. Joint display integration was used to enhance the findings. Results: Physical needs (median=3.75, IQR=1.50), health system informational needs (median=3.67, IQR=1.67), and psychological needs (median=3.60, IQR=1.85) were ranked highest, whereas intimacy-related needs (median=2.22, IQR=1.6) were the lowest ranked domain. Correlations of supportive care needs with demographics showed significant associations with employment status, hormonal therapy, and age. Cognitive needs were significantly higher in younger women, while receiving hormonal therapy was significantly associated with higher spiritual and family-related needs. Also, employed women showed less need for physical and practical support and patientclinician communication. Interview findings suggested expanded results in most domains and showed that needs differ at various points in the cancer journey. Chemotherapy treatment specifically was identified as the most difficult period, requiring the most support. Joint display integration was used to synthesise findings and showed nuanced insights across most of the domains, such as how women still face social stigma, and the important role of religion in their cancer journey. These insights highlight the need to redefine supportive care needs and develop a tailored, culturally specific framework to fit the context of the MENA region. Conclusion: The findings from the scoping review confirm that women’s unique needs in the MENA region require redefining and redevelopment of the Paterson framework and adaptation to this context. The mixed-methods design provided rich evidence that illuminated women's needs and could contribute to informing the design of culturally specific supportive care interventions for Saudi Arabian women and provide recommendations for service improvement.53 0Item Restricted Exploring Nonlinear Associations and Interactions of Risk Factors for Breast Cancer Incidence Using Machine Learning Approaches(Imperial College London, 2024-08) Alqarni, Lina; Heath Alicia; Berrington, AmyBACKGROUND: Breast cancer is influenced by a complex array of risk factors. This study aimed to identify nonlinear associations and interactions between various risk factors and breast cancer incidence using computationally efficient, interpretable methods. METHODS: Data from the Generations Study, a long-term prospective cohort of 104,423 women, were analysed. Risk factors evaluated included demographic, medical, reproductive, hormonal, and lifestyle variables. We compared the performance of traditional Cox proportional hazards models with tree-based methods, including Classification and Regression Trees (CART) and random forests, using the C-statistic. SHapley Additive exPlanations (SHAP) values were extracted to interpret random forest outputs, highlighting key risk factors and interactions. Stability selection was applied to enhance computational efficiency and identify the most stable and important variables. RESULTS: The multivariable Cox model achieved the highest predictive accuracy with C-index of 0.657, slightly outperforming the random forest model (C-index of 0.650). However, the random forest model revealed nonlinear associations and interactions not captured by the Cox model. Age, family history of breast cancer, and benign breast disease were among the most critical factors identified, with complex interactions noted between age, body mass index at entry, and family history with other risk factors such as hormone replacement therapy duration, oral contraceptive duration, and smoking pack-years. Stability selection effectively reduced the number of variables without compromising model performance. CONCLUSIONS: While linear models capture dominant associations, tree-based models like random forests offer additional insights into complex, nonlinear relationships among breast cancer risk factors, highlighting the potential for more personalised screening and prevention strategies16 0Item Restricted Advanced diffusion-weighted MRI of breast cancer: response to neoadjuvant chemotherapy and correlation with dynamic contrast-enhanced MRI(University of Leeds, 2025) Almutlaq, Zyad; Buckley, David; Wilson, DanielBackground: Previous studies showed promising applications of intravoxel incoherent motion (IVIM) and stretched-exponential (SEM) models of diffusion-weighted imaging (DWI) in breast imaging; however, their ability to predict early breast cancer response to neoadjuvant chemotherapy (NACT) was minimally investigated. Aims: To evaluate accuracy, bias, precision, and in-vivo repeatability of IVIM parameters estimated using different curve-fitting methods and determine the optimum for analysing the acquired clinical breast DWI data. To investigate the value of conventional monoexponential versus advanced (IVIM and SEM) DWI models parameters estimated from whole-tumour, tumour diffusion cold-spot, and perfusion hot-spot regions to assess early breast cancer response to NACT. To explore relationships between IVIM and dynamic contrast-enhanced (DCE)-MRI perfusion-related parameters, and between DWI diffusion coefficients and DCE-MRI cellularity-related measures in the same three tumour regions. Materials: MRI dataset of primary breast cancer patients acquired at pretreatment and after one and three NACT cycles. Simulated data represent IVIM parameter ranges observed in these patients. Results: Constrained oversegmented-fitting was the optimum IVIM curve-fitting method, producing parameter estimates with the smallest errors, highest precision, and best repeatability. Tumour volume was significantly larger in non-responders across all time-points and demonstrated reasonable predictive performance (AUC=0.84-0.88; p<0.05). The monoexponential model was unable to predict response (p>0.05), while IVIM and SEM models differentiated response groups at pretreatment tumour hot-spot regions and after one NACT cycle in three tumour regions, displaying reasonable predictive performance (AUC=0.71-0.79 at pretreatment, 0.71-0.83 after one cycle; p<0.05). IVIM and DCE-MRI perfusion-related parameters were uncorrelated (p>0.5), but statistically significant, moderate between-subject (r=0.405-0.461; p<0.05) and within-subject (rrm=0.514-0.619; p<0.05) correlations between diffusion coefficients and DCE-MRI cellularity-related measures were observed in the whole-tumour regions. Conclusion: IVIM and SEM models demonstrated better predictive capabilities for response than the monoexponential model. While IVIM and DCE-MRI perfusion-related parameters were uncorrelated, diffusion coefficients and DCE-MRI cellularity-related measures correlated.28 0Item Restricted Potential epigenetic biomarkers of circulating tumour DNA to improve detection of endocrine therapy resistance in breast cancer(Saudi Digital Library, 2023-03-07) Alahmari, Areej; Guttery, DavidBackground and aims: Endocrine therapy resistance is a major clinical problem and leading cause of metastatic breast cancer (MBC) death. Epigenetic changes via aberrant DNA methylation play an important role in therapy resistance. This thesis aimed to investigate aberrant methylation in oestrogen responsive elements (EREs) as a biomarker of hormone therapy resistance using MCF7 BC cell lines resistant to tamoxifen (TAMR-MCF7) and fulvestrant (FULVR-MCF7), with a view to utilising these signatures for early detection of hormone therapy resistance through circulating-tumour DNA (ctDNA). Methods: The four methylation conversion kits were compared for DNA recovery of to select the most efficient method for ctDNA methylation analysis. Aberrant DNA methylation was analysed in cell lines by shallow-depth whole genome bisulfite analysis (WGBS), and correlated with RNA-Seq data. Lastly, sets of primers were designed and validated the analysis of aberrant ctDNA methylation to apply to longitudinal plasma from patients with MBC. Results: The Premium bisulfite kit from Diagenode was the optimal kit for methylation conversion. EREs were hypermethylated and oestrogen target genes significantly downregulated in hormone therapy resistant cell lines. The hypermethylation phenotype existed more in ERE enhancers than promoters. EREs were not the dominant responsive elements in the aberrant DNA methylation analysis. FOX and AP-1 responsive elements were the top hits for hypermethylation in both resistant cell lines, while TEAD and MYC responsive elements were hypomethylated in FULVR and TAMR, respectively. The designed methylated-specific assays for OSMR promoter, and the enhancer of CBX4, TFF1, TRAF7 TERT, and RASA3 validated the enriched methylation level of these regions at resistant cell line. Conclusions: Results generated in this thesis has identified potential candidate regions that can be applied to longitudinal ctDNA samples from MBC patients to determine whether aberrant ctDNA methylation in EREs can be analysed as a marker of endocrine resistance.13 0Item Open Access Breast cancer extracellular vesicles transfer viral cargo following oncolytic virotherapy(2025) Alzahrani, Hyfa; Muthana, MunittaBackground: Breast cancer is the major kind of cancer among women in the United Kingdom. To treat radio-/chemo-resistant cancer as well as advanced illness, novel medicines are necessary. Oncolytic viruses (OV) are naturally cytotoxic and infect and kill tumour cells whilst sparing healthy tissues. The full mechanism by which this occurs remains to be elucidated, but it may in part be mediated by extracellular vesicles (EVs). EVs are nanosized, membrane-enclosed vesicles that contain molecular cargo. EVs can be taken up by cells, for instance immune cells, at local or distant sites, causing phenotypic changes in the recipient cells. We hypothesise that infection of breast cancer cells with an oncolytic virus causes release of EVs carrying viral and immunogenic cargo that leads to activation of anti-tumour immunity. Methods: To determine this, we infected breast cancer cells lines MCF-7 and MDA-MB-231 with the herpes simplex virus (HSV1716). EVs were isolated from the OV conditioned medium of infected cells and control cells by differential ultra-centrifugation (dUC). Characterization of these EVs' physical properties in order to determine the size ranges and rates of EV generation in breast cell lines and investigation on the oncolytic potential of EV-OV was carried out using Nanoparticle tracking analysis (NTA), Transmission electron microscopy (TEM) and mass spectroscopy. The antitumour efficacy of purified EVs was tested in an immunocompetent mouse model of mammary cancer using the luciferase labelled triple negative breast cancer cell line E0771. Results: EVs were isolated from MCF-7 and MDA-MB-231 cells after infection with OV, these are typically exosome-like with a diameter of ~ 150 nm. The purified EVs expressed exosome markers including CD9, CD63, TSG101 and carried viral and immune cargo. These EVs were internalised by breast cancer cells and inhibited tumour cell migration in vitro. Furthermore, systemic delivery of EVs derived from OV (EV-OV) infected breast cancer cells was able to inhibit primary tumour growth and pulmonary metastasis in vivo, more effectively that OV given alone. Conclusion: This indicates that EVs generated from cells that have been infected with OV may have antitumour characteristics. The use of EV-OV as a treatment with other cancer medications, such as immune checkpoint inhibitors, which may attract and activate T cells, changing a "cold" tumour into a "hot," tumor might lead to the creation of a new therapeutic approach for treating breast cancer.24 0