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Title: Studies relating to the breast, its tumours and fluids
Author: Miller, William Russell
ISNI:       0000 0001 3407 7637
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1988
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This thesis comprises 61 papers which describe work undertaken between 1972 and 1985. The research was performed in order to obtain basic information on the environment and the biochemical processes existing within the female breast. It was thereby hoped to achieve a better understanding of events which occur during the development of breast disease, particularly breast cancer. Hormones are involved not only in the natural development of normal breast but also in the aetiology of many breast abnormalities and, most importantly, in the continued growth of a proportion of breast cancers. A major aspect of the research described in this thesis is concerned with the measurement of steroid hormones, their metabolism and receptors in the breast, its tumours and secretions. Additionally studies have been performed to assess the significance of other markers of tumour behaviour and to determine whether agents such as LHRH analogues have direct effects within the breast. The potential of the breast to modify its own hormonal environment has been investigated by performing in vitro incubations with steroid precursors. Pathways leading to both active androgens and oestrogens have been identified. Biosynthesis of 5 reduced androgens occurs in all types of breast tissue but is particularly associated with apocrine differentiation. The production of oestrogen or "aromatization" was detected in a proportion of breast cancers but not in non-malignant tissue. The significance of tumour aromatase is controversial but it may be important in oestrogen-dependent cancers growing in post-menopausal women who have low circulating levels of oestrogen. In order to estimate levels of androgen precursors within the breast, measurements of DHA sulphate have been made in breast secretions obtained by nipple aspiration and breast cyst fluids. Remarkably high, but variable, concentrations have been detected. Further investigations of the composition of such breast fluids have shown them to have a distinctive composition in terms of ionic content, major types of immunoglobulins and concentrations of plasma-, platelet-associated and other proteins. Cyst fluids may be subdivided into two major populations which are lined by different epithelium and have a differing natural history. Several series of breast cancers have been analysed for either androgen receptors, progestogen receptors, cyclic AMP binding proteins, prostaglandins or expression of lectin binding. These have been suggested to be markers of metastatic potential or hormone-responsiveness. Inter-relationships have been made with oestrogen receptors and other tumour/patient characteristics but assessment of clinical value awaits patient follow-up. The possibility that polypeptide hormones have direct actions on the breast was investigated by culturing breast cancer cells with LHRH and its analogues. Marked inhibitory effects which appear to be mediated by a specific recognition mechanism have been demonstrated. These findings are reviewed in terms of their significance to the management of patients with breast disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (D.Sc.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Breast disease aetiology