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.　(c)　2025　Published　by　Elsevier　Ltd　on　behalf　of　European　Society　for　Clinical　Nutrition　and　Metabolism.