Rethinking Local Therapy in de novo Metastatic Breast Cancer: The Emerging Role of Radiotherapy

• Radiotherapy is emerging as a key component of locoregional treatment in de novo metastatic breast cancer, complementing systemic therapy in selected patients. • Biological mechanisms—including reduced metastatic seeding, modulation of the tumor microenvironment, and improved immune activation—support treatment of the primary tumor. • Retrospective evidence shows that radiotherapy improves local control and may extend survival in specific subgroups, particularly younger and oligometastatic patients. • Stereotactic radiotherapy offers ablative local control with minimal toxicity, representing a promising approach for oligometastatic disease. • Prospective, well-designed trials are urgently needed to clarify survival impact, refine patient selection, and optimize integration of radiotherapy with modern systemic treatments. De novo metastatic breast cancer (dnMBC) accounts for 3–10% of breast cancer diagnoses and shows distinct biology and prognosis from recurrent metastatic disease. Systemic therapies remain the cornerstone of treatment; however, the role of locoregional treatment (LRT), including surgery and radiotherapy, is controversial. Primary tumor resection may modulate systemic immunity, reduce metastatic seeding, and improve systemic therapy efficacy, but survival benefits remain inconsistent and patient selection is critical. Radiotherapy, alone or combined with surgery, improves local control and may extend survival in selected subgroups, particularly in oligometastatic patients and certain molecular subtypes. Advanced radiotherapy techniques such as stereotactic radiotherapy show promise for ablative treatment with minimal toxicity. Current evidence is largely retrospective and heterogeneous; prospective trials are urgently needed to clarify the impact of LRT on survival and quality of life in dnMBC. Optimal integration of local and systemic therapies requires individualized multidisciplinary decision-making to maximize patient benefit.