Liquid Biopsy Detection of Aberrant DNA Methylation as a Biomarker for Monitoring Reoccurrence in Trodelvy-Treated Triple-Negative Breast Cancer Patients

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptors, which renders it resistant to hormone-based and HER2-targeted therapies. The lack of targeted treatment options, along with a high risk of metastasis and a poor prognosis, underscores the urgent need for innovative diagnostic and monitoring strategies. Current gold-standard techniques, such as tissue biopsy and imaging, exhibit limitations in capturing tumor heterogeneity and the molecular evolution of the tumor during treatment. This study proposes a clinical trial to evaluate a six-gene liquid biopsy assay for detecting DNA methylation biomarkers in TNBC patients undergoing therapy with Trodelvy. Trodelvy, an antibody-drug conjugate that targets the TROP-2 protein, delivers SN-38, a potent chemotherapy agent, directly to cancer cells. Aim 1 focuses on validating the assay for differentiating TNBC from benign and normal tissue, while Aim 2 assesses its capacity to monitor biomarker levels and detect recurrence earlier than breast MRI. Liquid biopsy, a minimally invasive and cost-effective method for analyzing circulating blood tumor biomarkers, addresses the limitations of traditional tissue biopsies and imaging. By employing quantitative methylation-specific PCR (qMSP), this study seeks to establish liquid biopsy as a sensitive and specific tool for real-time monitoring of TNBC.