Complete NUB1 depletion in ER - negative breast cancer progression in paired primary–metastatic cases: a case series

Abstract Background NEDD8 ultimate buster 1 is an interferon-inducible tumor suppressor increasingly recognized as a prognostic biomarker in breast cancer. Low cytoplasmic expression correlates with aggressive disease, yet little is known about its dynamics between primary and metastatic estrogen-receptor-negative tumors. Objective The objective of this report is to compare NEDD8 ultimate buster 1 expression in paired estrogen-receptor-negative primary and metastatic breast cancer tissues, clarifying its role in tumor progression. Case presentation Two postmenopausal Caucasian women, patient A (ID: 14,024, aged 58 years) and patient B (ID: 20,996, aged 54 years), both diagnosed with estrogen-receptor-negative, human epidermal growth factor receptor 2-negative, grade III invasive ductal carcinoma, underwent NEDD8 ultimate buster 1 immunohistochemical analysis on matched primary breast tumors and corresponding metastatic lymph nodes. Both primary tumors exhibited high nuclear but low cytoplasmic NEDD8 ultimate buster 1, shifting to complete loss in metastases. The patient with higher primary cytoplasmic NEDD8 ultimate buster 1 had longer relapse-free and overall survival. Conclusion Loss of NEDD8 ultimate buster 1 in metastases may signal a transition from hypoxia-driven nuclear localization to unchecked metastatic progression. These findings highlight NEDD8 ultimate buster 1 as a potential prognostic marker and therapeutic stratifier, warranting larger studies to confirm its mechanistic and clinical relevance.