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Title: Alterations in the apoptotic-mitotic ratio : an early indicator of breast cancer sensitivity to tamoxifen
Author: Cameron, David
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1997
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The use of the Gompertz function, an accurate model of xenograft growth, could be used to predict subsequent tumour behaviour and thus identify responsive disease. The aim of this study was therefore to determine the relationship between tumour response to tamoxifen and changes in apoptosis and mitosis, to confirm their chronology and specificity in a model system, and to assess the possibility of identifying these changes in fine needle aspirates (FNAs) rather than biopsy material. In a cohort of 50 post-menopausal women with ER positive breast cancer treated with tamoxifen, the level of expression of both ER and the cell-survival gene bcl-2 predicted for tumour response. After three months' treatment there was a significant fall in proliferation in most tumours, but no overall change in apoptosis, as assessed by morphology. There was a significant trend for tumour response to correlate with the change in the apoptotic:mitotic ration (p < 0.05). To determine more accurately the timing of these changes, mice bearing xenografts of the ER positive ZR-75-1 and ER negative MDA-MB-231 breast cancer cell lines were treated with tamoxifen. After 2 days, an increase in apoptosis and the apoptotic:mitotic ratio was seen in the sensitive ZR-75-1 tumours (p < 0.05), and on day 7 there was also evidence for reduced proliferation (p < 0.05); however clear evidence of tumour regression only occurred after 14 days. On day 7 there was however a significant correlation between the apoptotic:mitotic ratio and the difference between the actual and the Gompertz-predicted tumour volumes (p < 0.02). These changes were not apparent in tamoxifen treated MDA-MB-231 tumours. No changes in bcl-2 expression were seen. Furthermore, although similar changes were seen in tumour FNAs, statistically they were not as significant, suggesting that they do not offer an alternative to repeat histological examination of the tumours. Early changes in the apoptotic:mitotic ratio during tamoxifen treatment of breast cancer may aid in the prediction of endocrine sensitivity.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available