This is a cluster of activities aimed primarily at developing better predictors for identifying women at increased risk of the disease, but also examining the side effect profiles and the durability of preventive interventions. Both tamoxifen and the aromatase inhibitor anastrozole are being studied. This is a central part of our programme, has the highest priority and includes many of the centre’s staff to work on different aspects of this area. Breast cancer is the commonest cancer in the UK and identifying high risk in individuals and developing preventive strategies is of central importance to the work of CR-UK, as well as our own.
The last quinquennium was devoted to assembling this cohort of 2,500 men managed by watchful waiting, producing papers based on clinical features, and creating TMAs from the ~1000 TURP specimens. We have just begun to use the pathology material, and will be analyzing the ability of IHC markers in the TMAs made from the TURP specimens to predict death from prostate cancer. Markers being investigated include the androgen receptor, Ki-67, pTEN, p53, p21, p16, E2F3, PKC-Z, hsp27, ARG2,ECAD, hepsin and T(4:6) translocation. Preliminary work by Dr Ho has shown that the material is suitable for mRNA expression analysis and this, plus methylation profiling will be a major activity outlined in the molecular epidemiology section. Markers identified using the TURP specimens, will be further studied and validated with needle biopsies in the remaining 1500 men in the cohort.
Given the uniqueness of this large cohort of patients treated by watchful waiting with available biopsy material, baseline PSA values and long term follow up, we propose to extend the cohort by another 1500 cases, to provide an additional validation cohort for the findings in the initial study.