Detection of MRD in TNBC Through Multi-Platform Molecular Biomarker Analysis

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The overarching goal of our research program is to understand the molecular heterogeneity of triple-negative breast cancer (TNBC), to identify and validate biomarkers that are both prognostic and predictive, and ultimately to optimize treatment for each patient based on the biology of her/his tumor. Towards this end, we have recently received funding to conduct a prospective investigator-initiated clinical trial entitled Adjuvant Intensification for Minimal Residual Disease in Triple-Negative Breast Cancer (AIM-TNBC) that is evaluating intensification of adjuvant systemic therapy in TNBC patients with residual disease after neoadjuvant systemic therapy. With industry support from Natera, Inc., we will use personalized circulating tumor DNA (ctDNA) analysis to identify patients with minimal residual disease and then randomize these high-risk patients to standard-of-care versus intensified adjuvant therapy. Our specific aims for this KIPM COBRE application are (1) to evaluate circulating tumor cells (CTCs) and non-coding RNAs (ncRNAs) in plasma-derived extracellular vesicles (EVs) as additional biomarkers of minimal residual disease to define a high-risk MRD signature in our prospective AIM-TNBC trial and (2) to understand how molecular biomarker information influences TNBC patients’ perception of individual relapse risk and willingness to accept adjuvant therapy. This work will ultimately improve our ability to risk-stratify TNBC patients and identify those who are likely to benefit from intensification of adjuvant systemic therapy. This goal is aligned with the KIPM COBRE’s mission of providing precision medicine in that it considers individual variability in the molecular composition of one’s disease and aims to tailor treatment towards each patient’s unique biology.