Breast MRI as a radiomic biomarker of immune enrichment in HER2+ breast cancer.

Abstract

e14281 Background: Trastuzumab is an important drug in the treatment (tx) of HER2+ breast cancer, but not all tumors are responsive. Immune-enriched tumors have a better response to tx, and a biomarker to identify these tumors would be valuable. Multiparametric functional MRI is a non-invasive technique that can assess the entire tumor without the sampling error of biopsy. In this pilot study, we evaluate breast MRI as a potential biomarker for tumor immune response to trastuzumab. Methods: Women with de novo cT1-2N0 HER2+ breast cancer were enrolled and received paired multiparametric breast MRI examinations (including DWI and DCE sequences) prior to and ~2 weeks after a single dose of trastuzumab, followed by surgery or biopsy (if additional neoadjuvant tx planned). Tumor peak signal enhancement ratio (SER) and mean apparent diffusion coefficient (ADC), reflecting tissue perfusion and tissue cellularity, were determined from the images. Pre- and post-tx tissue were immunologically profiled with TIL counts and an immune-focused RNA gene expression panel. SER and ADC were correlated with TIL and RNA gene expression using Spearman’s rho. Results: To date, 8 women have enrolled and 6 had pre- and post-tx tissue available. The primary endpoint was correlation between SER and ADC measurements with tumor TILs. Secondary endpoints included correlating SER with angiogenesis and inflammation markers and correlating changes in SER and ADC with apoptosis/cell death markers. About half of the patients had TIL-enriched (TIL≥ 50%) tumors at baseline, and after trastuzumab the majority of tumors remained enriched or had an increase in TILs. Results suggest that pre-tx ADC had a negative correlation with TILs by histology and gene expression, although correlations did not reach statistical significance in this small cohort. Results also suggest a strong correlation between pre-tx SER and VEGF-A (r = 0.83) with a trend towards significance (P = 0.10). A decrease in SER post-tx had a strong correlation with an increase in caspase 3 expression (r = -0.85, p = 0.05), which suggested tx effect. Conclusions: Functional MRI may provide a novel biomarker of breast tumor immune response to trastuzumab. Results from additional patients will be available at the meeting.