1. Biomarker studies in advanced breast cancer Dr Phil Murray (CHUFT) & Dr Dawn Farrar (UOE)

2. Metastatic Breast Cancer 10% of breast cancer. 30+ patients per year in Colchester All incurable but median survival 2 to 3 years with current therapy Endocrine Therapy Response takes up to 3 months Chemotherapy Toxic and expensive

3. STUDY RATIONALE Novel protein BORIS discovered in WBC of Breast Cancer Patients Ongoing Study suggests that BORIS could be a Biomarker for response to treatment in Primary Breast Cancer ? Role of BORIS in monitoring response in metastatic breast cancer ? Role in predicting response Identification of other proteins in metastatic breast cancer

4. STUDY DESIGN Endocrine Therapy: Research Bloods at baseline, 6 weeks and 12 weeks Clinical assessment, standard blood tests 6 12 Scan, Final clinical assessment 12 week Chemotherapy: Research Bloods at baseline, 3 weekly x 6 Clinical assessment, standard blood tests 3 weekly Scan, post 3 cycles, post 6 cycles Final clinical assessment post 6 cycles

5. BIOMARKER BENEFIT Prediction of response to therapy ER/PR Monitoring of response to therapy AFP Prediction of relapse CA 125

6. Current Status of Project Target of 30 patients Patient 31 just enrolled ( in six months) 11 endocrine, 20 chemotherapy 21 patients completed study 50% responding to treatment 50% progressing on treatment In next 3 months all samples collected and clinical responses documented

8. Scientific Perspective  Previous study- BORIS in WBC of breast cancer patients.  Investigate BORIS in WBC of patients with metastatic breast disease.  Find a new blood biomarkers to monitor treatment efficacy.

9. How? Blood collection Plasma WBC RBC WBCPlasma 2D gel electrophoresis Western Blot Analysis Immunocytochemistry Abundant protein depletion Western Blot Analysis 2D gel electrophoresis ? Cell smears Cell pellets X

10. WBC Boris? Identify/quantify BORIS levels - monitor pre & during treatment Comparison of ‘normal’ versus patient- pre-treatment Comparison of patient- pre-treatment versus final treatment New Biomarkers? Protein Profile of patients WBC Identify candidate blood biomarkers

11. Plasma/Serum markers? Currently used CEA (Carcineoembryonic antigen) CA 15.3 (Cancer Antigen breast) Candidate markers- - collaborative study with Metodiev group (Uni). Novel markers?

12. So far…………….. BORIS? New biomarker-2D gels? Normal (healthy) V Patient 005 Differences in protein profile? Protein ID? Protein absent?

13. So far…………….. 30 patients- 15 analysed pre-treatment. Candidate novel markers? Normal ABS 008ABS 009 Protein ID?

14. Patient 003 –pre-treatment v final treatment Pre-treatmentFinal Pre-treatmentFinal Protein ID?

15. Correlation with clinical data Chemotherapy or hormone therapy? Clinical response? Metastatic disease? BORIS and/or new biomarker?