Despite the recent advances in the detection, treatment and management of breast cancer, with an increasing range of hormonal, cytotoxic and more recently MAb targeted drug regimes available in the clinic, between 40% and 50% o f patients diagnosed will eventually die from this disease. Identification of biological factors which can function as reliable markers of both prognosis and chemoresponsiveness will allow for more precise targeting of treatment for individual breast cancer patients. During the course of this thesis the expression of a panel of MDR associated proteins was correlated with patient and tumour characteristics and relapse and overall survival in a series of invasive breast carcinomas. In order to address the multifactorial nature o f this disease, expression of individual proteins was analysed in relation to other markers. The results presented show that MRP-1 protein at diagnosis is an independent prognostic factor for overall survival in node positive breast cancer patients treated with CMF based chemotherapy, absence o f MRP-1 expression at diagnosis was significantly associated with increased overall survival. Results also indicated that this prognostic role of MRP-1 is likely to be stronger in patients with high grade i.e. grade III tumours. It also appeared that expression of cerbB-2 may be associated with reduced relapse and overall survival times in node positive patients treated with a CMF based chemotherapeutic regime. On preliminary analysis it appeared that the co-expression of MRP-1 with cerbB-2 in these patients may be a stronger prognostic tool than either cerbB-2 or MDR-1 alone. MDR-1 and survivin expression levels appeared to correlate in 71% of patients. There was no correlation observed between the other markers studied. Investigation of MDR-3 Pgp (which has recently been shown to transport several cytotoxic drugs) expression was also investigated in these breast cancer patients using a novel monoclonal antibody (MAb), 6/1G, which was produced during the course of this research; this MAb specifically recognises the MDR-3 encoded gene product. Preliminary results indicate that MDR-3 Pgp was expressed in a high proportion (73.3%) of invasive breast carcinomas studied. The exact significance of this expression and the contribution, if any, of MDR-3 Pgp in the resistance of breast cancer or other solid cancers further investigation. Immunocytochemical studies with antibody 6/1G on a panel of B cell malignancies suggest that MDR-3 Pgp may possibly be associated with a more malignant phenotype in B-CLL and that its expression may be associated with certain stages of B cell development. In an attempt to identify new breast cancer drug resistance associated antigens, MAb 5C3 was generated using paraffin wax embedded formalin fixed archival breast tumour tissue from a biopsy showing no P-170 or MRP-1 expression, as an immunogen. Immunohistochemical analysis with this novel MAb of pre and post treatment tumours however, did not reveal any apparent association with resistance for the antigen recognised by antibody 5C3. Extensive immunocytochemical and Western blot analysis of both cell lines and tissues with antibody 5C3 suggested that the reactive antigen did not appear to be tumour specific and was more likely to be an unidentified breast antigen also expressed in the normal breast. Results o f internal sequencing analysis of a 175Kda band which was obtained from immunoprécipitation of the ductal breast carcinoma cell line, ZR-75-1 revealed that MAb 5C3 is recognising a heteropolymer of cytokeratin 6 and cytokeratin 9. The expression o f this novel complex in human breast cancer should be further investigated to address any possible prognostic implications.