Background/Objectives: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy have become the standard of care for HR+/HER2− metastatic breast cancer. Given the metabolic functions of CDK4/6 and the endocrine activity of adipose tissue, body mass index has been proposed as a potential prognostic or predictive factor in this setting. This systematic review aimed to summarize current evidence on the association between BMI and treatment outcomes in HR+/HER2− MBC patients receiving CDK4/6i. Methods: A systematic literature search was conducted in PubMed and Scopus databases, covering publications from 2015 to 2025. We included real-world studies and clinical cohorts reporting survival outcomes of HR+/HER2− MBC patients treated with CDK4/6i in relation to BMI and other body composition parameters. Results: From 69 records identified, 14 studies met the inclusion criteria. Findings were heterogenous; four studies reported improved survival outcomes in higher BMI patients, whereas most identified no significant association. Studies incorporating computed tomography-based metrics demonstrated that body composition parameters such as visceral adiposity and skeletal muscle area were more reliable predictors of prognosis than BMI alone. Conclusions: Our findings indicate that BMI as a standalone metric is an insufficient predictor of clinical outcomes or treatment response for those receiving CDK4/6i, highlighting the need for precise body composition evaluation. More detailed anthropometric and metabolic profiling could clarify the clinical significance of adiposity in HR+/HER2− MBC.

Background/Objectives: The prognostic and predictive role of BMI in patients with HR+/HER2– MBC remains controversial, particularly in the era of CDK4/6 inhibitors. This study aimed to evaluate the association between baseline BMI and clinical outcomes in patients treated with palbociclib in a real-world setting. Methods: We conducted a multicenter retrospective observational cohort study including 326 patients with HR+/HER2− MBC treated with palbociclib in combination with endocrine therapy across six oncology centers in Romania. Only patients who received palbociclib for at least three months were included. Patients were stratified according to BMI into <25 kg/m² and ≥25 kg/m² groups. PFS and OS were the primary endpoints, while ORR and CBR were secondary endpoints. Results: Among the 326 patients, 66.6% were classified as overweight or obese (BMI ≥25 kg/m²). Median PFS was 23.66 months in the BMI <25 group and 26.78 months in the BMI ≥25 group, with no statistically significant difference (HR 0.86, 95% CI 0.62–1.20; p = 0.373). Median OS was not reached in the BMI <25 group and was 43.73 months in the BMI ≥25 group, also without significant difference (HR 0.82, 95% CI 0.52–1.30; p = 0.397). ORR (29.07% vs. 28.89%) and CBR (90.7% vs. 88.3%) were comparable between BMI groups. In multivariate analysis, liver metastases and brain metastases were independently associated with worse outcomes, whereas BMI was not an independent prognostic factor. Conclusions: In this selected real-world cohort of patients with HR+/HER2− MBC who tolerated at least three months of palbociclib, baseline BMI was not associated with treatment response, PFS, or OS. While clinically informative, these results should not be interpreted as definitive evidence that body weight has no influence on palbociclib efficacy, given the methodological constraints of the analysis. BMI alone may be insufficient to capture the complex interplay between body composition and treatment outcomes, highlighting the need for more refined biomarkers of body composition in this setting.

Background/Objectives: Patients with metastatic breast cancer and visceral crisis are systematically excluded from clinical trials, leaving clinicians without evidence-based therapeutic guidance. To the best of our knowledge, no published reports have described the use of combined chemo-immunotherapy in mTNBC complicated by hepatic visceral crisis. Case presentation: We report the case of a 45-year-old woman with PD-L1-high recurrent TNBC who presented with acute, life-threatening hepatic failure. Laboratory evaluation revealed marked transaminase elevation, cholestasis, rising bilirubin levels, and clinical deterioration consistent with hepatic visceral crisis. Due to severe hepatic impairment, a sequential therapeutic strategy was adopted: treatment was initiated with dose-reduced weekly paclitaxel (80% of the standard dose), and pembrolizumab (200 mg every three weeks) was introduced at the fourth cycle. Shortly after immunotherapy initiation, the patient experienced rapid clinical improvement accompanied by significant biochemical recovery and radiologic tumor regression. Although disease progression occurred after four months, hepatic visceral crisis did not recur. Discussion: This case questions the conventional restriction of immunotherapy in the setting of severe hepatic dysfunction. The rapid biochemical recovery observed after pembrolizumab initiation suggests that immunologic antitumor activity may be preserved despite significant hepatic impairment. Furthermore, the high PD-L1 expression in this patient indicates that its predictive value may extend even to the context of visceral crisis. Conclusions: Our findings suggest that immunotherapy in combination with chemotherapy may represent a feasible therapeutic strategy in selected patients with PD-L1-high mTNBC presenting with hepatic visceral crisis.

Background/Objectives: The prognostic and predictive role of BMI in patients with HR+/HER2− MBC remains controversial, particularly in the era of CDK4/6 inhibitors. This study aimed to evaluate the association between baseline BMI and clinical outcomes in patients treated with palbociclib in a real-world setting. Methods: We conducted a multicenter retrospective observational cohort study including 326 patients with HR+/HER2− MBC treated with palbociclib in combination with endocrine therapy across six oncology centers in Romania. Only patients who received palbociclib for at least three months were included. Patients were stratified according to BMI into <25 kg/m² and ≥25 kg/m² groups. PFS and OS were the primary endpoints, while ORR and CBR were secondary endpoints. Results: Among the 326 patients, 66.56% were classified as overweight or obese (BMI ≥ 25 kg/m²). Median PFS was 23.66 months in the BMI < 25 group and 26.78 months in the BMI ≥ 25 group, with no statistically significant difference (HR 0.86; 95% CI 0.62–1.20; p = 0.373). Median OS was not reached in the BMI < 25 group and was 43.73 months in the BMI ≥ 25 group, also without a significant difference (HR 0.82; 95% CI 0.52–1.30; p = 0.397). ORR (29.07% vs. 28.89%) and CBR (90.70% vs. 88.33%) were comparable between BMI groups. In multivariate analysis, liver metastases and brain metastases were independently associated with worse outcomes, whereas BMI was not an independent prognostic factor. Conclusions: In this selected real-world cohort of patients with HR+/HER2− MBC who tolerated at least three months of palbociclib, baseline BMI was not associated with treatment response, PFS, or OS. While clinically informative, these results should not be interpreted as definitive evidence that body weight has no influence on palbociclib efficacy, given the methodological constraints of the analysis. BMI alone may be insufficient to capture the complex interplay between body composition and treatment outcomes, highlighting the need for more refined biomarkers of body composition in this setting.