Abstract

Abstract Introduction: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are important in the treatment of hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). Previous studies have shown that CDK4/6is affect metabolic processes and cell metabolism, including adipogenesis, lipid synthesis, and glucose regulation. Obesity has been associated with worse survival in breast cancer. We aimed to assess the effect of body mass index (BMI) on survival outcomes in patients treated with CDK4/6is for MBC. Methods: Patients diagnosed with metastatic HR+/HER2-negative BC and who were treated with palbociclib, ribociclib, or abemaciclib from 6/10/2015 to 12/28/2022 were selected from the Montefiore Health system database and followed until 3/24/2023. The patients were divided into three groups according to BMI level as follows; normal: 18.5-24.9 kg/m2, overweight: 25-29.9 kg/m2 and obese: ≥ 30 kg/m2. Patients were also stratified by BMI measured after 3 months of therapy. Characteristics of the patients and tumors in the subgroups were compared using chi-squared/Fisher’s exact test for categorical data and Kruskal-Wallis/Wilcox signed rank tests for continuous data. Kaplan-Meier and Cox proportional hazards analysis were used to compare overall survival (OS) and progression free survival (PFS). Results: Among 221 patients, 66 were normal weight, 78 were overweight, and 77 were obese. There was no statistically significant difference in clinicopathological characteristics among the cohorts. Neither BMI measured at baseline nor after 3 months of therapy had any association with OS (P = 0.8 at baseline and P = 0.1 after 3 months) or PFS (P = 0.4 at baseline and P = 0.6 after 3 months). Multivariable analysis showed no statistically significant association between BMI and worse OS (HR: 1.1 for overweight, P = 0.7; and 0.96 for obese, P = 0.9) or worse PFS (HR: 0.9 for overweight, P = 0.8; and 0.76 for obese, P = 0.5). Multivariate analysis revealed a significant effect of obese BMI after 3 months of treatment on OS (HR: 0.48, P = 0.035) but not on PFS (HR: 0.88, P = 0.8). Overweight BMI after 3 months of treatment was not found to have a significant effect on OS (HR: 0.49, P = 0.063) or PFS (HR: 0.89, P = 0.9). Conclusion: The clinical effectiveness of CDK4/6is was not found to be influenced by BMI measured prior to therapy; however, there may be an association between improved OS and obese BMI after 3 months of treatment. Median OS and PFS in patients with MBC comparing different BMI groups (normal, overweight, and obese) at baseline prior to therapy and after 3 months of therapy. Table 1 Baseline characteristics of patients with MBC comparing different BMI groups (normal, overweight, and obese) at baseline prior to therapy and after 3 months of therapy. Table 2 Table 3 Multivariable analysis of OS and PFS for patients with MBC comparing different BMI groups (normal, overweight, and obese) at baseline prior to therapy and after 3 months of therapy. Citation Format: Frank Zhang, Jesus Anampa Mesias. The impact of body mass index on CDK4/6 inhibitor treatment survival outcomes in metastatic breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-09.

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