Clinical, histological and immunological studies in human breast cancer
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Part 1 (Volume 1) A clinico-pathological investigation into the significance of metastases and reactive changes in regional lymph nodes draining breast cancer. In the introduction, an extensive review of the literature is presented. The original work, which involved review of clinical records, histological techniques, radio-isotope scanning and data processing, is then described. The principal findings were: 1. Lower axillary sampling was only useful for indicating prognosis in primary breast cancer if more than one node was found. However, a trial of sampling versus clearance demonstrated that, if done correctly, sampling was equally capable of detecting metastases. 2. Nodal metastases were shown to correlate significantly with tumour size, tumour border, histological grade, oestrogen receptor status and duration of symptoms. 3. A grading system incorporating all the major histological reactive changes was shown to be an effective prognostic index, but favourable reactive changes were found to be associated with favourable tumour factors, suggesting that these nodal reactions may merely reflect the nature of the tumour rather than represent an effective host response. Furthermore, sinus histiocytosis, a reactive change which is widely recognised to be a favourable prognostic factor, was shown to be induced by breast biopsy. 4. The prognostic significance of lymphocytic infiltration of breast cancer was found to be dependent on reactive changes in the regional nodes. 5« The inaccuracy of clinical examination in detecting axillary metastases or assessing reactive changes was confirmed. Axillary lymphoscintigraphy was found to be no more effective than clinical examination in detecting nodal metastases, but a computer-based combination analysis of several parameters related to metastases was a significant improvement. Part 2 (Volume 2) An investigation into some of the properties of monocytes and macrophages in breast cancer patients and normal subjects. In the introduction, a review of the literature is presented. The original work, which involved the identification and characterisation of monocytes and macrophages using rosetting techniques and immunoperoxidase staining, is then described. The principal findings were: 1. Peripheral blood monocytes from breast cancer patients were activated in terms of lysozyme content and Fc (IgG) receptor expression. 2. Tumour-infiltrating macrophages showed depressed lysozyme and alpha-1-antitrypsin contents and defective phagocytosis of IgG-coated red blood cells. 3« A higher macrophage content was found in tumours with a poor prognosis when compared to tumours with a good prognosis. These findings suggest that tumour-infiltrating macrophages are selectively depressed, accounting for their lack of anti-tumour activity in vivo. 4. Studies on normal monocytes revealed that the third component of complement can stimulate lysozyme synthesis, and that phagocytosis may induce the release of alpha- 1-antitrypsin. Both of these findings may represent important regulatory mechanisms in monocyte/macrophage physiology.