Thesis (Ph. D.)--University of Wisconsin--Madison, 2002. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 145-165).

Thesis (Ph. D.)--University of Washington, 2006. / Vita. Includes bibliographical references (leaves 41-49).

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 73-84).

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2008. / Vita. Includes bibliographical references.

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A research report submitted to the Faculty of Medicine university of tho Witwatersrand, Johannesburg, in partial fulfilment of the requirements for the Degree of Master of science in Medicine. / Breast cancer is a major health problem, afflicting up to 1 in 9 women in developed countries with Western diet and life style. While screening programs have led to earlier diagnosis, including diagnosis at a pre-invasive stage in a number of women, the majority of patients with breast cancer still present with clinically detectable, invasive breast cancer, which even if clinically localised still carries the risk of systemic micrometastases, Such patients have been shown to benefit both in terms of disease free as well as of overall survival from the addition of adjuvant systemic treatment. The identification of progostic factors which can be used to tailor specific forms of adjuvant treatment to the patient's disease has been an important goal of breast cancer research during the last 20 years. A particularly important goal is the early identification of poor risk patients, who may benefit from aggressive intervention with intensive chemotherapy, While many prognostic markers, including nodal status, hormone-receptor-status, ploidy and growth fraction and the expression of various oncogenes and proto-oncogenes by the tumor cells have been proposed as prognostic factors, the results, to date, have been equivocal for a number of these. Recently there has been much. interest in the prognostic importance of cerbB- 2 protein in breast cancer. Most of these studies have concentrated on immunohistochemically stainable e-erb-2 in tumor tissue. This dissertation focusses on the prognostic impact of the soluble c-erbB-2 protein in the serum of breast cancer patients treated at the Breast Clinic of tne Johannesburg Hospital and University of the Witwatersrand. The results of this investigation have been reported under the title "Soluble c-erhB-2 fragment in Serum Correlates With Disease Stage and Predicts for Shortened Survival in Patients with Early Stage and Advanced Breast Cancer" by H. Kandt, L. Seymour & W.R. Bezwoda, Published in British Journal of Cancer, Vo170 p739-742" 1994. / Andrew Chakane 2018

Introduction: Radiosensitivity (RS) of South African women with breast cancer was investigated as it has been studied in European women, but to date this has not been studied in South African women. The micronucleus assay was used to determine the amount of DNA damage on lymphocytes of breast cancer patients. Materials and Methods: The first component to this study involved the collection of blood samples from breast cancer patients and healthy individuals. For the second component, blood samples from breast cancer patients were collected before and after the completion of radiotherapy (RT). A centromeric micronucleus assay using the Fluorescent in situ Hybridisation (FISH) pancentromeric probe was used to investigate the origin of the micronuclei (MN) and to distinguish between radiation-induced [centromere negative (CM-)] and spontaneous [centromere positive (CM+)] MN. Results: Micronucleus frequencies were slightly higher in breast cancer patients than those observed in lymphocytes of healthy donors. This was noted for the different radiation doses and indicated a trend towards an enhanced chromosomal radiosensitivity in this cancer population. Results were compared before and after radiotherapy. The micronucleus scores for the 0 Gy (sham irradiated samples) were significantly higher (p < 0.05) post radiotherapy. This is an expected result as ionising radiation causes more damage. However, blood samples from post-therapy patients, were shown to have fewer MN after subsequent in vitro 2 Gy and 4 Gy irradiation respectively. When assessing the centromeric micronucleus assay results, a significantly (p < 0.05) higher number of CM- MN was observed than CM+ MN after RT, thereby indicating that ionising radiation causes more breaks in the chromosomes (clastogenic damage). Discussion and Conclusion: This study demonstrates that a group of South African breast cancer patients have slightly higher micronucleus frequencies compared to a population of healthy women, indicating a trend towards a higher sensitivity to radiation.