Imaging of tumour microvasculature using high-resolution contrast-enhanced ultrasound together with markers of proliferation, angiogenesis and vascular mimicry to characterise the response to neoadjuvant chemotherapy in triple-negative breast cancer

Triple-negative breast cancer (TNBC) represents 10-15% of all breast cancer cases diagnosed annually in the UK. Treatment frequently involves neoadjuvant chemotherapy, immunotherapy and surgical excision. Current imaging techniques to monitor and predict disease response have limited accuracy. New high-resolution contrast-enhanced ultrasound (CEUS) techniques have the ability to image gross tumour morphology and its microvasculature to visualise angiogenesis.

This research aimed to characterise microvessel density (a surrogate marker for angiogenic activity) as quantified by imaging features using high-resolution CEUS and biomarkers of proliferation, angiogenesis and vasculogenic mimicry during neoadjuvant chemotherapy (NACT). The study also investigated whether germline mutations, as well as the basal type phenotype, correlated with microvessel density and tumour response.

Two patients with triple-negative breast cancer and planned neoadjuvant treatment were recruited and, at specific points of NACT, underwent high-resolution CEUS and immunohistochemistry of tissue samples to assess their response to NACT. Both patients (TNBC001 and TNBC002) demonstrated an encouraging response during neoadjuvant treatment radiologically and histologically. TNBC001 has been found to have complete pathological response, and TNBC002 is awaiting completion of the research study.

This preliminary study indicates that high-resolution CEUS is a potentially valuable tool to monitor treatment response during NACT in patients with TNBC with a demonstrable reduction in microvessel density. The results presented here provide the evidence required to initiate a larger-scale study, which will be needed to change clinical practice.