EVOLUTION VERSION 1
Research type
Research Study
Full title
Evolution of resistance to systemic therapies in patients with breast cancer.
IRAS ID
153142
Contact name
Jillian Noble
Contact email
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
It is unknown if resistance to first-line systemic therapies in patients with metastatic breast cancer emerges by selection of sub-clones in the primary tumour disseminated with first metastases or as a consequence of random genetic/epigenetic changes originating after metastases are established. Whole-body diffusion-weighted magnetic resonance imaging (WB-DWI) is emerging as a valuable technique for monitoring the response and progression of malignancy, including liver metastases. The objective is to apply WB-DWI alongside the routine imaging of patients requiring systemic therapy for metastatic breast cancer to compare the time to progression of individual liver metastases within and between patients following stable disease or partial response to palliative systemic therapy.
The primary purpose is to use the within-patient and between-patient variation in time to progression of individual metastases to test the likely origin of resistance. A high level of synchrony or concordance in time to progression would not be consistent with random genetic/epigenetic changes within metastases as the dominant driver of resistance, at least at the time of first relapse following primary treatment. The implication would be that resistance to neo-adjuvant and adjuvant systemic therapies for patients with early breast cancer, and possibly for other cancers, is a function of resistant sub clones present in the primary tumour and shed at the time of first metastasis. The secondary purpose is to conduct the same comparison as above in the estimated 50% of patients who also have skeletal metastases, compare the within-organ and between organ (liver and bone) variation in time to progression of individual metastases and subsequently to test if concordance weakens after further lines of systemic therapy.
REC name
London - Brent Research Ethics Committee
REC reference
14/LO/2111
Date of REC Opinion
10 Dec 2014
REC opinion
Further Information Favourable Opinion