Bridging the Gap in Breast Cancer Dormancy: Models, Mechanisms, and Translational Challenges

Breast cancer (BC) poses a significant clinical challenge due to late metastatic recurrence, driven by dormant disseminated tumor cells (DTCs). This review emphasizes the urgency of addressing tumor dormancy to reduce metastatic relapse, a major contributor to BC mortality. DTCs evade conventional therapies and immune surveillance, reactivating unpredictably, thus necessitating targeted strategies. Current research is fragmented, with conflicting data, inadequate models, and a lack of biomarkers hindering progress. This review synthesizes these gaps and proposes actionable priorities, advocating for integrated, standardized approaches. It highlights the roles of single-cell multi-omics, spatial transcriptomics, and humanized long-term models in unraveling dormancy mechanisms. The review also emphasizes macrophage-targeted therapies, dormancy-specific trials, and biomarker validation, offering paths to clinical translation. Ultimately, this work emphasizes the urgent need for integrated multi-omics approaches, including single-cell and spatial transcriptomics, combined with advanced computational analysis. Moreover, this review critically analyzes the existing research landscape, meticulously identifying key gaps, and proposing concrete, forward-looking directions for both fundamental research and clinical translation in the challenging field of BC dormancy.