Local Control of Advanced Breast Cancer-Debate in Multidisciplinary Tumor Board.

: In Romania, breast cancer is the second most common cancer, the third leading cause of cancer death, and the most prevalent cancer overall. De novo advanced-stage breast cancer often presents in clinical practice, and treatment decisions are best made in a multidisciplinary tumor board (MTD) involving surgeons, radiotherapists, and medical oncologists. Significant advances in systemic therapies, particularly in progression-free survival (PFS) and overall survival (OS), have surpassed traditional palliative mastectomy and radiotherapy for local control. Therefore, the purpose of this study is to emphasize the importance of the initial choice of treatment for patient prognosis. : We expose two cases of patients with de novo severe, advanced-stage, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and their management and outcome using cyclin-dependent kinase (CDK) 4/6 inhibitor and radiotherapy. An extensive review of the literature from the past five years was also conducted. : The role of palliative mastectomy is diminishing, as many patients are opting for novel therapies, including cyclin-dependent kinase (CDK) 4/6 inhibitors, which may improve quality of life. : First-line therapy for locally advanced breast cancer has suffered changes due to the implementation of systemic targeted therapy. However, drug resistance-either de novo or acquired-remains a critical consideration. MTD discussions and informed patient decisions are essential to achieving a personalized, evidence-based treatment outcome.