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Title: The response to the primary systemic therapy of breast cancer
Author: Keen, Jeremy C.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1998
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The primary tumour response in terms of reduction in volume was monitored by serial breast ultrasound scans in 95 patients treated with the anti-oestrogen tamoxifen and in 15 patients treated with the cytotoxic agents adriamycin and cyclophosphamide. After three months of treatment 74% of patients treated with tamoxifen and 93% of those treated with chemotherapy had demonstrated a response. Serial tumour fine needles aspirates were also taken during treatment from subgroups of patients undergoing either endocrine or cytotoxic therapy. These were analysed by flow cytometric methods that were initially validated in human cancer cell lines grown both in tissue culture systems and as xenografts. The results derived from patients receiving chemotherapy, whilst interesting, were limited by the small number of patients studied and an almost universally good response to treatment. However, larger numbers of patients and a broad spectrum of tumour responses produced more meaningful results in the tamoxifen-treated group. Several biological markers such as the expression of oestrogen receptors, P-glycoprotein, Ki-Sl and Bcl-2 were significantly related to the observed clinical response after multivariate analysis. Pre-treatment oestrogen receptor expression, measured by two different methods, correlated with the subsequent reduction in tumour volume after tamoxifen treatment with a high degree of significance. P-glycoprotein expression was significantly higher in post-treatment samples from tumours that had not responded to tamoxifen in comparison to responding tumours. This has potentially important implications for tumour sensitivity to second line treatment with certain cytotoxic agents. The expression of both Ki-Sl, a nuclear antigen acting as a marker of proliferation, and Bcl-2, a marker of cellular resistance to cell death by apoptosis, were observed to significantly decrease in responding tumours. These effects occurred independently and it is proposed that this may reflect two different pathways through which tamoxifen may exert its anti-tumour action, both by decreasing proliferation and/or increasing susceptibility to apoptosis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available