| Summary: | Radiotherapy (RT) is a component of treatment for breast cancer in more than 50% of cases. Patients are selected for RT on the basis of limited clinical and histopathological factors with no reference to the molecular phenotype of tumours. Breast cancer is a highly heterogeneous disease and some tumours are refractory to RT treatment. Selection of patients for RT using predictive markers may improve RT efficacy and cancer outcomes. The aims of the work described in this thesis were to identify and test potential predictive markers for RT in cancer treatment. I examined whether the classic histopathological breast cancer subtypes or the levels of expression of five molecular markers, 26S proteasome, GRP78, HJURP, IGFlR and PARPl, would provide predictive insights into response to RT in the context of both cultured breast cancer cell lines, and archival patient samples supported by clinical follow up. Clonogenic survival assays revealed that cell lines representative of luminal or basal breast cancers did not display subtype specific responses to RT. Similarly, expression levels of 26S proteasome, GRP78, HJURP, IGFlR and PARPl did. not correlate with specific responses to RT in cell lines. In breast cancer patients who underwent RT high expression of 26S proteasome was significantly associated with increased rates of local recurrence. High expression of HJURP was associated with reduced rates of local recurrence, as was high expression of PARPl. Importantly, these associations were not found in patients who were treated without RT, suggesting that these markers provide predictive in sights into RT response, rather than prognostic insights into the likelihood of local recurrence overall. Finally, high expression of 26S proteasome was also found to be associated with increased rates of local recurrence in bladder cancer patients, suggesting that this marker may have predictive value for RT in a range of cancer settings.
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