New data reveal that vepdegestrant, a PROTAC-based selective estrogen receptor degrader, demonstrates superior efficacy over fulvestrant in advanced ER-positive, HER2-negative breast cancer harboring acquired resistance mutations. This breakthrough advances therapeutic options for hormone receptor-positive breast cancer, potentially overcoming treatment resistance and improving patient outcomes. The novel degrader's enhanced ability to target mutant estrogen receptors represents a significant pharmacological development within endocrine oncology.