This article presents a novel method for the thermophoretic glycan profiling of extracellular vesicles (EVs) for the management of triple-negative breast cancer (TNBC). The method, called EVLET (Extracellular Vesicle Lectin-Based Thermophoretic Assay), combines vibrating membrane filtration (VMF) with thermophoretic amplification to rapidly and sensitively profile EV glycans in TNBC plasma. The EVLET system enables the detection of TNBC-associated glycans with high accuracy, achieving 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of therapeutic response. The EV glycan signature, derived from the weighted sum of three lectins, shows potential for predicting TNBC progression. The EVLET system is cost-effective, rapid, and suitable for clinical use, offering a non-invasive approach for cancer management. The study demonstrates that EV glycans can serve as valuable biomarkers for TNBC diagnosis, monitoring, and prognosis. The EVLET system is validated using a pilot cohort study with 135 plasma samples, showing its effectiveness in differentiating TNBC from other breast cancer subtypes and healthy donors. The EVLET system is also shown to be effective in assessing therapeutic response and predicting prognosis in TNBC patients. The study highlights the potential of EV glycans as non-invasive biomarkers for cancer management and the importance of developing practical analytical methods for their detection. The EVLET system offers a promising solution for the clinical application of EV glycans in cancer management.This article presents a novel method for the thermophoretic glycan profiling of extracellular vesicles (EVs) for the management of triple-negative breast cancer (TNBC). The method, called EVLET (Extracellular Vesicle Lectin-Based Thermophoretic Assay), combines vibrating membrane filtration (VMF) with thermophoretic amplification to rapidly and sensitively profile EV glycans in TNBC plasma. The EVLET system enables the detection of TNBC-associated glycans with high accuracy, achieving 91% accuracy for TNBC detection and 96% accuracy for longitudinal monitoring of therapeutic response. The EV glycan signature, derived from the weighted sum of three lectins, shows potential for predicting TNBC progression. The EVLET system is cost-effective, rapid, and suitable for clinical use, offering a non-invasive approach for cancer management. The study demonstrates that EV glycans can serve as valuable biomarkers for TNBC diagnosis, monitoring, and prognosis. The EVLET system is validated using a pilot cohort study with 135 plasma samples, showing its effectiveness in differentiating TNBC from other breast cancer subtypes and healthy donors. The EVLET system is also shown to be effective in assessing therapeutic response and predicting prognosis in TNBC patients. The study highlights the potential of EV glycans as non-invasive biomarkers for cancer management and the importance of developing practical analytical methods for their detection. The EVLET system offers a promising solution for the clinical application of EV glycans in cancer management.