Body mass index and clinical outcomes in breast cancer patients undergoing endocrine therapy: A meta-analysis and Mendelian randomization study.

Objective: The relationship between breast cancer prognosis, Body Mass Index (BMI), and endocrine therapy outcomes remains inconclusive. This study examines BMI's impact on survival outcomes in breast cancer patients receiving endocrine therapy through Mendelian randomization (MR) and a comprehensive clinical data review.

Methods: A meta-analysis of clinical studies up to January 2024 investigated the association between obesity and the efficacy and safety of endocrine therapy. Additionally, a two-sample MR approach using genetic variants evaluated the causal effect of BMI on survival in breast cancer patients undergoing endocrine therapy.

Results: Meta-analysis of eight studies (n = 12,673) found that BMI generally does not affect therapy outcomes. However, subgroup analysis showed that overweight patients on anastrozole had shorter disease-free survival (DFS) than normal-weight patients (Hazard Ratio (HR) = 1.21, P = 0.03), increased fatigue (Risk Ratio (RR) = 0.91, P = 0.03), and higher nausea with cyclin-dependent kinase 4/6(CDK4/6)inhibitors (Risk Ratio, RR = 0.69, P < 0.0001). Normal-weight patients on tamoxifen had a greater risk of bone pain (RR = 1.25, P = 0.03). Further MR analysis revealed no causal link between BMI and 5-year or 15-year survival rates in endocrine-treated patients (5-year HR = 0.7923, 95 % Confidence Interval (CI)[0.2053, 3.0581], P = 0.7355; 15-year HR = 0.9793, 95 % CI [0.7121, 1.3469], P = 0.898).

Conclusion: Current meta-analysis and MR findings suggest no significant link between BMI and the overall efficacy of endocrine therapy in breast cancer. However, BMI should be considered in anastrozole therapy due to differential effects on DFS and adverse events.