BRIDGE version 1
Research type
Research Study
Full title
Breast Cancer Immune, Drug and Gene (BRIDGE) Study
IRAS ID
330219
Contact name
Kalnisha Naidoo
Contact email
Sponsor organisation
King’s College London
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
5 years, 0 months, 1 days
Research summary
Sentinel lymph nodes (SLN) in the armpit (‘axilla’) are the first site that breast cancer spreads to (‘metastasis’). These SLN are linked, in a chain, to other axillary lymph nodes (ALN). SLN can help patients by generating an anti-tumour immune response but can also harm patients by permitting further axillary spread. In fact, the presence of axillary metastasis significantly decreases survival.
Our study includes patients with all types of breast cancer (i.e. oestrogen (ER)-receptor positive; Her2-positive; and triple-negative). We aim to discover how metastatic cancer in the first SLN affects downstream ALN. We will study how cancer changes ALN structure and function (‘microenvironment’). Specifically, we will determine how/if cancerous ALN secrete soluble factors that travel to an adjacent non-cancerous ALN, altering the microenvironment to attract incoming tumour.
First, we will compare archival cancerous and non-cancerous ALN, for which we have follow-up data, using a technique called ‘immunohistochemistry’. We aim to identify target molecules (‘biomarkers’) that alter the ALN microenvironment, thereby decreasing survival.
Second, we will harvest one cancerous and one non-cancerous node prospectively from breast cancer patients who are having their ALN routinely removed. Using a modified heart-lung bypass machine, we will pump fluid (containing soluble factors) from the cancerous node into the non-cancerous node and study how the non-cancerous ALN microenvironment changes in response to this. We will do this using different laboratory techniques, including in vitro culture, microscopy, histology, immunohistochemistry, immunofluorescence, flow cytometry and/or multi-omic technologies (including shotgun proteomics and next generation sequencing of nucleic acids).
Finally, we will inject the perfusion fluid into mice. Unlike humans, mice are exposure-naïve. We can be sure, therefore, that any changes we see are due to the injected soluble factors.
Ultimately, we hope to identify biomarkers of metastatic risk and novel drug targets to improve how we treat patients with breast cancer.
REC name
North West - Greater Manchester East Research Ethics Committee
REC reference
24/NW/0079
Date of REC Opinion
25 Mar 2024
REC opinion
Further Information Favourable Opinion