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Biomarker studies in advanced breast cancer Dr Phil Murray (CHUFT) & Dr Dawn Farrar (UOE) 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 Chemotherapy Response takes up to 3 months Toxic and expensive 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 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 BIOMARKER BENEFIT Prediction of response to therapy ER/PR Monitoring of response to therapy AFP Prediction of relapse CA 125 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 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. How? Blood collection Plasma WBC RBC X WBC Cell smears Cell pellets Plasma 2D gel electrophoresis Abundant protein depletion Western Blot Analysis Western Blot Analysis Immunocytochemistry 2D gel electrophoresis ? WBC Boris? Identify/quantify BORIS levels - monitor pre & during treatment New Biomarkers? Protein Profile of patients WBC Comparison of ‘normal’ versus patient- pre-treatment Comparison of patientpre-treatment versus final treatment Identify candidate blood biomarkers Plasma/Serum markers? Currently used CEA (Carcineoembryonic antigen) CA 15.3 (Cancer Antigen breast) Candidate markers- collaborative study with Metodiev group (Uni). Novel markers? So far…………….. BORIS? New biomarker-2D gels? Protein ID? Protein absent? V Differences in protein profile? Normal (healthy) Patient 005 So far…………….. 30 patients- 15 analysed pre-treatment. Candidate novel markers? Protein ID? Normal ABS 009 ABS 008 Patient 003 –pre-treatment v final treatment Protein ID? Pre-treatment Final Protein ID? Pre-treatment Final Correlation with clinical data Chemotherapy or hormone therapy? Clinical response? Metastatic disease? BORIS and/or new biomarker?