Great advances have been made in the molecular characterisation of advanced breast cancer (ABC). Still, clinical practice has not changed in terms of assessment of response to therapy. Radiologic imaging and clinical examination help determine disease burden and treatment efficacy. However, imaging heavily relies on the expertise of the radiologist and oncologist and has high intra- and inter-reader variability. Circulating tumor cells (CTCs) enumeration with CellSearchâ has confirmed independent prognostic value compared to conventional radiology and serum markers such as CA15-3. Similarly, quantification of circulating tumor DNA (ctDNA) has also prognostic value in ABC. ctDNA analysis further provides critical information on the mutational status of specific genes which can predict sensitivity to specific targeted therapeutics.
The SCAN-B-rec (NCT03758976) is a prospective multi-center observational study that aims to explore the value provided by ctDNA analysis to determine treatment efficacy when compared to CTCs and conventional radiological imaging in a “real-world” setting. A total of 350 patients with pathologically-confirmed ABC will be recruited. Plasma ctDNA will be extracted and analysed before treatment start (T0) and after three months of therapy (T1). The relative change in mutant allele frequency (MAF) between these two time-points will be calculated. Response to treatment will be defined using pre-specified cut-offs. A comparison with response to treatment according to conventional radiological imaging (RECIST criteria) and CTC enumeration at the same time points will be performed. The primary objective is to establish the prognostic value of ctDNA to predict overall survival. The study will also explore the added value provided by ctDNA mutational analysis to determine biomarkers of sensitivity and resistance to targeted therapeutics approved to treat ABC or other solid tumors that could be used “off-label”. We expect that ctDNA quantification will give a more accurate read-out of treatment response, providing better prognostic information in ABC as well as information on drug sensitivity/resistance in a large proportion of ABC patients.
SCAN-B-rec (NCT03758976).
Lund University Hospital (Region Skane).
BioCARE, Cancer Fonden, ALF (Region Skåne) and Svenska Läkaresällskapet.
A. Bosch: Advisory board meetings: Pfizer, Novartis in Sweden. These have been non-remunarated. L. Saal: CEO: AGA Diagnostics. All other authors have declared no conflicts of interest.