published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Medicine / Master / Master of Research in Medicine

published_or_final_version / Public Health / Master / Master of Public Health

published_or_final_version / Pathology / Master / Master of Philosophy

published_or_final_version / Pharmacology and Pharmacy / Doctoral / Doctor of Philosophy

published_or_final_version / Public Health / Master / Master of Public Health

Breast cancer comprises of 22.9% of all cancers worldwide in females. In the year 2008, it has caused 458,503 deaths worldwide. De-regulation of transcription factors has been shown to play an important role in the progression of breast cancers. Snail and TWIST genes have been found to promote epithelial-mesenchymal transition (EMT). It has been suggested that the level of expression of each of these genes correlates with poor prognosis in different types of solid tumors. For breast cancer, the up-regulation of Snail was associated with recurrence and higher tumor grade, while the up-regulation and up-regulation of TWIST was associated with shorter survival and metastatic development. However, in recent studies conflicting results have been observed. Our collaborator had analyzed mRNA expression data obtained from the Gene Expression Omnibus (GEO) database together with patient survival data from the breast cancer cohort datasets, and found that expression of Snail when stratified against TWIST expression levels or vice versa, gave more significant association with survival than when expression levels of Snail or TWIST was considered on their own. To investigate whether these findings could be demonstrated at a protein level, we performed imrnuno-histochemisty analysis on breast cancer samples in tissue microarray blocks. Nuclear and cytoplasmic scores of TWIST were successfully assessed separately in 114 invasive breast cancer patients. The Snail scores were obtained from previous studies. As Snail and TWIST are both transcription factors, nuclear expression of each was examined for correlation of Snail and TWIST with pathological features and patient survival. Our results showed that nuclear Snail expression did not correlate with survival (p=0.498) but when stratified with nuclear TWIST, high levels of nuclear Snail expression associated with poorer survival in patients with low nuclear TWIST expression (p=O.2l2), though not statistically significant which agreed with the mRNA results of our collaborator. For nuclear TWIST expression, association with survival was in reverse from that of the mRNA findings. Low expression levels of TWIST mRNA was associated with shorter survival, however immuno-histochemistry showed that high levels of nuclear TWIST expression marginally correlated with poorer survival (p=O.079). Low levels of cytoplasmic TWIST expression on the other hand, correlated with poorer survival in patients (p=O.024), and when stratified against high nuclear Snail, expression was associated with shorter survival (p=O.022), which is in keeping with mRNA findings. The results show that Snail and TWIST expression gave more prognostic value when considered together than when considered individually, which suggests that Snail and TWIST might be functionally similar in the promoting of EMT mediated breast. It also highlights the importance of nuclear and cytoplasmic localization by immuno-histochemistry in evaluating results and in assessing its role in promoting breast cancer progression. In conclusion Snail and TWIST should be considered together for prognostication of breast cancer as they may complement each other in predicting the progression of the disease. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Breast cancer is the leading malignancy among Asian women, which often have a young disease onset pattern. Germline mutation in high-penetrance breast cancer susceptibility genes are known to play an important role in early disease onset, but only 5-10% cases are associated with mutations in BRCA1 or BRCA2 gene. By contrast, common variants might also have deleterious effect in breast cancer development. A BRCA2 coding SNP rs1799944 (N991D) was found to have no association with breast cancer risk among Hong Kong Chinese population, but significantly confers a better disease-free survival in the breast cancer patients. In this study, the relevance of this association was further verified by using an enlarged sample pool of Hong Kong Chinese breast cancer patients. A total of 483 Hong Kong Chinese breast cancer subjects were unselectively recruited between 1976 and 2011. SNP N991D genotype of patients was determined by Taqman allelic discrimination genotyping assay. Pearson’s Chi-Square and logistic regression were used to assess the association between the SNP genotypes and breast cancer disease characteristics. Kaplan-Meier survival and multivariate Cox proportional hazards regression analyses were used to examine the relationship between the SNP genotypes and overall survival as well as disease-specific survival of the patients. Of the 449 breast cancer patients successfully genotyped, 16.9% had heterozygous AG genotype and 0.4% had rare homozygotes GG genotype. The variant allele G had a MAF of 8.91% among Hong Kong Chinese breast cancer patients. Patients harboring the SNP N991D variant allele G had longer disease-free survival period compared to the non-carriers (HR = 0.28; 95% CI: 0.09 – 0.92; p=0.036), which was confounded by patients’ local and/or distant metastasis status at diagnosis stage (HR=3.00; 95% CI: 1.57 – 5.74; p=0.001). Although N991D carriers also had a better overall survival pattern than the non-carriers, the difference between them was not statistically significant. Moreover, the association of SNP N991D variant allele G carriers with a lower disease recurrence rate (OR= 0.27; 95% CI: 0.82 - 0.90; p=0.023) was owing to the association of the variant with fewer distant metastases (OR = 0.11; 95% CI: 0.02 – 0.83; p=0.010) but not the local relapse status (OR= 0.38; 95% CI: 0.85 – 1.67; p=0.182) of the clinical outcome when comparing to the non-carriers. In conclusion, the missense BRCA2 N991D SNP has indicated an association with better clinical outcome as well as disease-free survival in Hong Kong Chinese breast cancers. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Background: Breast cancer is the most common cancer diagnosis in women. Treatments of breast cancer are constantly developing which leads to a high rate of surviving women. Being affected of breast cancer can result in many intense feelings and a changed body. Most of the women who get affected by breast cancer are treated with surgical treatment. One operation that is used is mastectomy, an surgical operation where one or both breasts are being removed. This may lead to several feelings, changed body image and the women have to adapt to their new body. Aim: The aim of the overview was to explore women's experiences, thoughts and emotions after a mastectomy, due to breast cancer. Method: A literature overview study based on seven qualitative and three quantitative studies. Results: In the result four themes emerged, The body betrays and is no longer complete, You are not the same person anymore, Femininity and sexuality are lost and The social limitations. Conclusion: One of the main findings shown in the result was how the mastectomy changed the women's body image. It seemed to be difficult to accept the changed body, which became a constant reminder of the disease. The women no longer recognized themselves and therefore had a hard time when it came to show themselves in front of people in the surroundings. The women also felt limitations in social situations and the body became an obstacle; they did not feel comfortable, isolated themselves and avoided everyday activities. This is important to acknowledge as a nurse and be able to give adequate support in both short term and long term.