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 Plasm

aWBC

RBC

WBC Plasma

2D gel electrophoresis

Western Blot Analysis

Immunocytochemistry

Abundant protein depletion

Western Blot Analysis

2D gel electrophoresis ?

Cell smearsCell pelletsX

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-treatment

Final

Pre-treatment

Final

Protein ID?

Protein ID?

Correlation with clinical data

Chemotherapy or hormone therapy?

Clinical response?

Metastatic disease?

BORIS and/or new biomarker?