Fig. 1: Overview of how breast cancer dormancy fuels recurrence.

The emergence of dormant breast cancer (BC) cell populations occurs as an adaptive response to dormancy-inducing stressors within the primary tumour microenvironment, including hypoxia, extracellular matrix (ECM) remodelling, and anti-cancer therapies. Dormant disseminated tumour cells (DTCs) employ various survival mechanisms, mainly DNA damage repair, autophagy, immune evasion, and transcriptional and epigenetic reprogramming. These adaptations enable dormant DTCs to persist undetected in circulation while remaining biologically active. Upon reaching various metastatic niches, such as the bone (most common), lungs, liver, and brain, disseminated tumour cells (DTCs) may encounter specialised microenvironments that provide dormancy-supporting signals. These cues enable DTCs to persist in a quiescent state for extended periods. However, in response to reactivation signals such as inflammation, niche remodelling, or immunosuppression, DTCs can exit dormancy, resume proliferation, and give rise to overt metastases, ultimately leading to disease relapse. Although several potential therapeutic strategies have been suggested and are currently being attempted [185], we suggest that targeting the survival mechanisms sustaining BC dormancy holds significant promise for preventing recurrence.