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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. [ABSTRACT FROM AUTHOR]

Introduction Ovarian cancer (OC) is the second most common gynecological cancer and the leading cause of death in the United States (1, 2). Its high mortality rate is mainly due [...], Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage-like TAMs were localized in the center of spheroids and secreted EGF, which upregulated [α.sub.M][β.sub.2] integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM. Moreover, EGF secreted by TAMs activated EGFR on tumor cells, which in turn upregulated VEGF/VEGFR signaling in surrounding tumor cells to support tumor cell proliferation and migration. Pharmacological blockade of EGFR or antibody neutralization of ICAM-1 in TAMs blunted spheroid formation and ovarian cancer progression in mouse models. These findings suggest that EGF secreted from TAMs plays a critical role in promoting early transcoelomic metastasis of ovarian cancer. As transcoelomic metastasis is also associated with many other cancers, such as pancreatic and colon cancers, our findings uncover a mechanism for TAM-mediated spheroid formation and provide a potential target for the treatment of ovarian cancer and other transcoelomic metastatic cancers.