Transcript Biomarker studies in advanced breast cancer

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?