Introduction: A higher body mass index (BMI) has been associated with a better response and overall survival in patients with lung cancer or melanoma receiving immune checkpoint inhibitors (ICIs). Pembrolizumab has been approved for the use of breast cancer, but its relationship with BMI on survival outcomes is unclear., Methods: We conducted a retrospective, propensity score-matched cohort study using the TriNetX Analytics Network database, which contains de-identified data from over 120 participating healthcare institutions. We included all adult female patients with breast cancer who received pembrolizumab. We excluded patients who were prescribed endocrine or human epidermal growth factor receptor 2-targeted therapies. We compared the 1-year all-cause mortality between patients who were overweight or obese (BMI ≥25 kg/m2) and those who were normal weight (BMI <25 kg/m2). We matched patients on predetermined variables including age, race, breast cancer-directed therapy, cardiovascular and diabetes medications, and underlying comorbidities., Results: We identified 1,628 eligible patients, of whom 1,163 had a BMI ≥25 kg/m2 and 465 had a BMI <25 kg/m2. After propensity score matching, 410 patients in each cohort were well balanced for demographics, breast cancer-directed therapy, and underlying comorbidities. The mean ages for patients with BMI ≥25 kg/m2 and BMI <25 kg/m2 were 56.7 ± 14.0 and 56.9 ± 15.0, respectively. Over a median follow-up of 1 year, 28 and 53 patients died in the BMI ≥25 kg/m2 and BMI <25 kg/m2 cohorts, respectively. Patients with BMI ≥25 kg/m2 had a 49% lower risk of all-cause mortality compared with those with BMI <25 kg/m2 (hazard ratio, 0.51 [95% CI: 0.33-0.81])., Conclusions: A BMI ≥25 kg/m2 was associated with a lower all-cause mortality among breast cancer patients receiving pembrolizumab., (© 2024 S. Karger AG, Basel.)