Knowledge gaps and future perspectives for the definition, diagnostics and treatment of isolated locoregional recurrent breast cancer.

Isolated locoregional recurrence (ILRR) of breast cancer (BC) is associated with a poor prognosis and a high risk of distant metastasis (DM) and death. As ILRR occurs in around 0.5-1.5% of BC patients annually, and the overall prevalence of primary BC is high, the absolute number of ILRR BC patients is substantial. Diagnosing a second BC event can be challenging, particularly distinguishing between a true recurrence (TR) and a second primary (SP). This distinction is clinically relevant, as TRs are associated with a poorer prognosis, especially when presenting as regional recurrences, and require a more challenging therapeutic approach compared to SPs. The radiologic work-up of suspected BC recurrence depends on the tumor location (breast, chestwall, or regional), clinical presentation, prior treatment characteristics, and should include systemic staging given the substantial risk of synchronous distant metastases. Robust scientific evidence and guidelines on locoregional and systemic treatment of ILRR of BC are lacking. Consequently, ILRR management currently relies on expert opinion, and therefore may vary between institutions. This review aims to provide an overview of current knowledge on definition, diagnostic workup, staging, locoregional treatment, and systemic treatment of ILRR. Furthermore, ongoing clinical research and future research perspectives to improve the diagnostic work-up and multimodality treatment of patients with ILRR will be outlined.