Measuring the Response to Neo-Adjuvant Chemotherapy for Breast Cancer using Novel Ultrasound Device and Quantitative Multi-Omics Data - A pilot study

The tumor microenvironment in breast cancer varies within the tumor and amongst the various tumor subtypes, accounting for the heterogeneity of breast cancers. The initiation and progression of breast tumors rely heavily on the interface between the breast tumor and its surrounding, otherwise considered healthy parenchyma. The peritumor is functionally and phenotypically dissimilar from the intra-tumor and the healthy parenchyma and is known to vary spatially around the tumor boundary. The tumor and peritumor interactions could suggest tumor evolution and invasion, potentially influencing cellular migration and proliferation in malignant breast tumors. This interaction could also provide some insight into the response to NACT, and subsequently developing strategies to improve therapeutic response.

Objectives:

1. Map and quantify the tumor microvasculature of breast tumors in 3D using ultrasound imaging and correlate with 3D shearwave (SWE) elastography and 3D ultrasound texture before, during, and post-NACT.

2. Measure the expression of adhesion molecules, tumor-infiltrating lymphocytes, tumor-associated macrophages, and fibroblasts intra- and peri-tumorally before, during, and post-NACT.

3. Quantify the expression of genes in the tumor and circulating blood using whole-exome/genome sequencing and correlate against imaging and immune readouts before, during, and post-NACT.