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 Response takes up to 3 months Chemotherapy 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 WBCPlasma 2D gel electrophoresis Western Blot Analysis Immunocytochemistry Abundant protein depletion Western Blot Analysis 2D gel electrophoresis ? Cell smears Cell pellets X

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

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? Normal (healthy) V Patient 005 Differences in protein profile? Protein ID? Protein absent?

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

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

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