Abstract PO1-18-11: Imaging of tumour microvasculature using high-resolution contrast enhanced ultrasound together with markers of proliferation/angiogenesis/vascular mimicry to characterise response to NACT in TNBC
Authors: Rait Jaideep , Garrett Michelle , Harper-Wynne Catherine , Saw Sonia , Tang Mengxing , Palanisamy Priya , TOULEMONDE Matthieu , Cox Karina 
Published: May 2024

Background: In the UK, triple-negative breast cancer (TNBC) comprises 10-15% of breast cancer diagnoses annually. TNBC represents a clinical challenge due to a lack of expression of three treatable drug targets, namely oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER-2). The mainstay of treatment involves the use of neoadjuvant chemotherapy (NACT) followed by surgical excision where up to 50% of patients will achieve a pathological complete response (pCR). The addition of neo-adjuvant immunotherapy may increase the pCR rate to 60%. The presence of lymphatics and blood vessels within/around malignant tumours plays a role in cancer progression as does the formation of new blood vessels (angiogenesis). The vascular endothelial growth factor (VEGF) family and their receptors (VEGFRs) play an important role in angiogenesis as well as promoting the growth and survival of cancer cells. VEGFR is frequently overexpressed in TNBC and promotes changes in vascular endothelial cells, the basement membrane and the surrounding extracellular matrix. Co-expression of epidermal growth factor receptor (EGFR) and VEGFR enhances tumour growth and angiogenesis in an autocrine and paracrine manner. An alternate mechanism for tumour microcirculation in tumours is vasculogenic mimicry (VM). This is distinct from classical tumour angiogenesis. The presence of VM is associated with poor overall survival in breast cancer patients and anti-angiogenic treatment of TNBC may even promote tumour growth, proliferation and metastasis by stimulating VM. Conventional imaging techniques such as B-mode ultrasound and MRI are commonly used to monitor disease response in the breast but have limited accuracy in predicting pCR or residual disease. High-resolution contrast-enhanced ultrasound (HRCEUS) may offer a more accurate test to monitor TNBC response to NACT. This method utilises intravenously injected microbubbles, which consist of a gas core with an outer shell of lipid/albumin to image tumour microvasculature as well as gross tumour morphology. Trial Design: Single-centre study to evaluate HRCEUS to image the microvasculature of TNBC tumours in patients undergoing (NACT) and correlate imaging results with established markers of angiogenesis, proliferation and vasculogenic mimicry. Eligibility Criteria: Female, 18 to 60 years, histologically confirmed invasive TNBC with planned NACT, able to consent and in the Investigator’s opinion, adhering to the trial recommendations and governance. Aims:

To investigate if imaging changes in the tumour microvasculature indicate a response to NACT and are reflected in the expression of proliferative markers.

To determine whether changes in the tumour microvasculature and disease response are driven by angiogenesis +/- VM.

To investigate whether overall disease response and changes in the microvasculature are influenced by the basal type phenotype or germline mutations in BRCA 1/2.

Investigate patient satisfaction with the contrast ultrasound test.

Statistical Methods:

Quantify HRCEUS imaging characteristics of microvasculature at 3 treatment points. Compare this with the results of conventional imaging and the histopathological results of surgical excision at the end of NACT.

Quantify immunohistochemical markers of angiogenesis, proliferation and VM at three treatment points and compare this with HRCEUS.

Determine phenotype of all cases using immunohistochemistry to identify the basal Perform subtype analysis to assess if the basal phenotype is associated with imaging and immunohistochemical changes in the microvasculature during NACT.

Test patients for germline BRCA1/2 gene mutations. Perform subtype analysis to assess if germline BRCA1/2 mutations are associated with imaging and immunohistochemical changes in the microvasculature during NACT.

Present accrual (2 patients) and target accrual (5 patients) Contact details: j.rait@nhs.net

Citation Format: Jaideep Rait, Michelle Garrett, Catherine Harper-Wynne, Sonia Saw, Mengxing Tang, Priya Palanisamy, Matthieu TOULEMONDE, Karina Cox. Imaging of tumour microvasculature using high-resolution contrast enhanced ultrasound together with markers of proliferation/angiogenesis/vascular mimicry to characterise response to NACT in TNBC [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-18-11.