Background: Although CDK4/6 inhibitors combined with endocrine therapies have improved outcomes in HR+ HER2-negative metastatic breast cancer, predictive biomarkers for treatment response and adverse effects remain limited. This study assessed the prognostic and predictive value of large unstained cells (LUC), a subset of white blood cells that may reflect immune status or treatment response. Methods: A retrospective analysis of 210 patients with HR+ HER2-negative metastatic breast cancer treated with CDK 4/6 inhibitors between 2021 and 2024 was conducted. Clinical data, including demographics, tumor characteristics, and treatment regimens, were analyzed. Based on LUC levels, progression-free survival (PFS), overall survival (OS), and adverse events were evaluated. Results: The cohort had a median age of 57, of which 78% were postmenopausal. Common metastatic sites included bone (67%) and liver (24%). At a median follow-up of 18.5 months, the PFS and OS rates were 65% and 83%. Patients with low LUC levels had significantly shorter PFS (OR: 1.91; p = 0.014) and OS (OR: 2.39; p = 0.012), while high LUC levels correlated with a lower incidence of grade 3 neutropenia (OR: 0.49; p = 0.017). Liver metastasis and prior treatments were also linked to shorter survival. Conclusions: LUC levels emerge as a promising biomarker for predicting survival outcomes and the risk of neutropenia in HR+ HER2-negative metastatic breast cancer patients treated with CDK 4/6 inhibitors and endocrine therapy, showing their potential to guide personalized treatment approaches.

Background and Objectives: Although breast cancer is the most common type of cancer among women, bilateral breast cancer (BBC) remains exceedingly rare. BBC can present as either synchronous (SBBC) or metachronous (MBBC) disease. Data regarding the clinical characteristics of BBC are limited. In this study, we aimed to share our multicenter, retrospective experience on the clinicopathological and demographic features of SBBC and MBBC, their survival outcomes, and the factors influencing survival, in light of current knowledge. Material and Method: A total of 125 patients who were treated and followed between 2015 and 2024 across six different centers were included in the study. The patients were categorized into synchronous (SBBC) and metachronous (MBBC) groups. Their clinicopathological characteristics were analyzed, along with disease-free survival (DFS) and 5-year overall survival (OS) outcomes. Results: DFS was 5.7 years in the SBBC group and 5.6 years in the MBBC group (p = 0.95). The 5-year OS rate was 95.2% in the MBBC group and 80.7% in the SBBC group (p = 0.035). Hormone receptor negativity was identified as an independent risk factor for lower DFS in the overall patient cohort (HR: 0.55, 95% CI: 0.31–0.98, p = 0.04). Conclusion: Significant differences were found between the SBBC and MBBC groups in terms of hormone receptor status, presence of an invasive lobular carcinoma component, recurrence/metastasis status, and molecular subtype discordance between the two primary tumors. Although DFS did not significantly differ between the groups, the 5-year OS was significantly higher in the MBBC group. In multivariate regression analysis, hormone receptor negativity was identified as an independent risk factor for decreased DFS among all BBC patients. Our study is noteworthy for shedding light on the clinical features of BBC in the context of current knowledge and for its multicenter design.

Purpose: CDK4/6 inhibitors require meticulous monitoring due to their potential to cause hematological toxicities and hepatotoxicity. This study evaluates the safety of combining CDK4/6 inhibitors with palliative radiotherapy in patients with metastatic hormone receptor-positive and HER2-negative breast cancer. Patients and Methods: This study included 188 patients treated with CDK4/6 inhibitors between January 2021 and June 2024. Data on patient demographics, tumor characteristics, and treatment interventions were extracted from medical records. The primary focus was on the incidence of grade ≥ 3 hematologic toxicities and hepatotoxicity, assessed according to CTCAE 5.0 criteria, in those receiving concurrent palliative radiotherapy. Results: With a median follow-up of 18.5 months, the 18-month PFS and OS rates were 67% and 85%, respectively. The median age was 57.5 years, and 79% of patients were post-menopausal. Bone and liver metastases were present in 66% and 23% of patients, respectively. Concurrent palliative radiotherapy was administered in 25% of the cohort. The incidence of grade ≥ 3 hematologic toxicity was comparable between those who received radiotherapy and those who did not. Ribociclib use was associated with lower rates of grade 3 hematologic toxicity (OR: 0.37), neutropenia (OR: 0.41), dose interruptions (OR: 0.30), and dose reductions (OR: 0.37). Pre-menopausal status was linked to fewer dose reductions (OR: 0.17). Rates of treatment interruption, dose reduction, and withdrawal were 55%, 24%, and 2%, respectively. Conclusions: The concurrent use of CDK4/6 inhibitors and palliative radiotherapy does not increase the incidence of hematological adverse events in patients with metastatic breast cancer.

Background: Undifferentiated pleomorphic sarcoma (UPS) is the most common adult soft tissue sarcoma subtype, with heterogeneous survival despite optimal surgery. We evaluated whether the preoperative maximum standardized uptake value (SUVmax) on ¹⁸ F-fluorodeoxyglucose PET/computed tomography ( ¹⁸ F-FDG PET/CT) is independently associated with overall survival (OS) in surgically resected UPS. Methods: This retrospective cohort study included 79 patients with localized UPS who underwent curative resection between 2015 and 2023. Preoperative SUVmax, tumor grade (French Federation of Cancer Centers Sarcoma Group), tumor size, and Ki-67 index were assessed. Cox proportional hazards regression was used to identify independent prognostic factors for OS. Results: The median age was 59 (range: 18–92) years; 53.2% of patients were male, and 59.5% of tumors were high grade. The median tumor size, Ki-67 index, and SUVmax were 60 mm, 60%, and 10, respectively. At a median follow-up of 58.9 months, median OS was not reached. In univariable analysis, tumor size ( P = 0.007), Ki-67 ( P = 0.001), SUVmax [hazard ratio: 1.08 per unit, 95% confidence interval (CI): 1.04–1.10, P = 0.001], and high grade ( P = 0.003) were associated with worse OS. In multivariable analysis, only SUVmax remained independently associated with OS (adjusted hazard ratio: 1.06 per unit, 95% CI: 1.02–1.10, P = 0.002), whereas grade, size, and Ki-67 did not retain significance. Conclusion: Preoperative ¹⁸ F-FDG PET/CT SUV _max is independently associated with OS in surgically resected UPS and provides prognostic information beyond conventional clinicopathological parameters.