1. An introduction to Breast Cancer and Unmet Clinical Needs
Michael Douek
Reader in Surgery & Consultant Surgeon
King’s College London
Guy’s and St Thomas’ Hospitals
Benny, thank you , this is my second trip to Enschede and we now now have a successful collaboration which I hope we can strengthen even further.

2. Guy’s & St Thomas’
12,500 members of Staff
1100 beds
400 new breast cancer patients pa
230 immediate breast reconstructions
5 breast surgeons / 6 plastic surgeons
1 nurse consultant / 5 breast nurses

5. Breast Cancer Commonest cancer in women
49,900 new cases per year in UK (30%)
12,400 deaths pa (17%)
1:9 women
UK highest incidence in the world

6. Patient management of cancer
Detection
of gene
activity
Tumor
cells
RNA
Gene
expression
profile
DIAGNOSIS
TREATMENT

7. Changing Landscape Global Financial crisis
Reduced funding opportunities
Merging of grant bodies in the USA
Ageing population
Modern clinical trials changing
Early generation: 1 group stratified by ER
Modern trials: ‘individualised medicine’
3 groups: ER+/HER2-; HER2+; triple negative;
Device trials
Lets consider the changing landscape

8. Major Unmet Clinical Needs
Contrast agents for Breast MRI
New techniques for sentinel node biopsy
Devices for assessment of tumour margins
Percutaneous ablation / resection of small tumours
Devices for breast reconstruction
Drugs for triple negative tumours
60-100%
70-80%
60%
30-40%
20-25%
20%
Lets consider the imaging modalities available:

9. Novel technique for SLNB

10. The combined technique using a radioisotope (technidium -99m labelled albumin) and the injection of blue dye, allow the surgeon to use a gamma probe to find the node intra-operatively, and to easily identify the blue node as you can see here.
Both dyes are injected subcutaneously, usually periareolar or subareolar.
But it is of course the histological examination of the lymph nodes that establishes lymph node status. Sentinel nodes that contain a macrometastasis (over 2mm in size) or a micrometastasis (between 0.2 and 2mm in size ) are regarded as involved and an axillary node clearance is recommended.

11. Prototype:
SQUID
Processor
Design brief: to be able to detect 100 μg of magnetic dye 30 mm from the probe’s tip. 11

12. Hand-held magnetometer
Magnetic Tracer
Sienna+
black/brownish liquid, which is a composed of a suspension of carboxydextran-coated superparamagnetic iron oxide nanoparticles
CE marker injectable device

14. Inclusion criteria: Exclusion criteria:
Norfolk and Norwich University Hospitals (UK)
Bromfield Hospital (UK)
Guy’s & St Thomas’ (UK)
MST, Enschede (NL)
Non-randomized trial (patients received both techniques)
Centers selected for experience with SLNB and high numbers
As trial coordinator responsible for designing protocol, acquiring approvals etc
Inclusion criteria:
Patients with primary cutaneous melanoma scheduled for SLNB
Clinically AJCC stages IB-IIC
Exclusion criteria:
Intolerance to iron, dextran compounds and / or blue dye
Patients who cannot / do not receive radioisotope for SLNB
Patient with iron overload disease
Patients with pacemakers or other implantable devices
Patients who had previous surgery or a scar between the primary site and likely draining lymph node field(s)
Patient with pre-existing lymphoedema at the primary biopsy site
Patients who subsequently shown to have more than stage III disease
SLNB identification rate 97%
Sample size n=160
80% Power; limit difference -5%

15. Future development in breast cancer – unmet needs
Patient centred:
Identify clinical need / strength of product
Value / cost
Funding / timeline
Regulatory / IP aspects
Recognise benefit of robust clinical trials in the longer term
Lets consider the imaging modalities available: