Background/Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.

Background and Objectives: Major stressful life events may influence psychological adaptation in patients with cancer, although their clinical relevance remains uncertain. We aimed to estimate the prevalence of self-reported major stressful life events near cancer diagnosis and examine their association with anxiety, depressive symptoms, and illness-related cognitions. Materials and Methods: This multicentre cross-sectional study included 275 consecutive adults with solid malignancies from three Romanian oncology centres between 17 and 28 August 2026. Participants completed the Hospital Anxiety and Depression Scale (HADS), the Illness Cognition Questionnaire (ICQ), and a study-specific item on major stressful life events. Results: Of 275 participants, 252 answered the life-event item and 92 reported an event, corresponding to a prevalence of 36.5% (95% CI 30.8–42.6). Anxiety scores were nominally higher among patients reporting an event (median 7.0 vs. 5.5, p = 0.035), but this difference was not significant after correction for multiple comparisons (adjusted p = 0.174). Depression and ICQ subscale scores did not differ significantly. Poorer ECOG performance status and several sociodemographic characteristics were associated with greater psychological distress. Conclusions: Major stressful life events were commonly reported but were not significantly associated with current psychological distress or illness-related cognitions after multiplicity adjustment. These findings support multidimensional psychosocial assessment in oncology care.