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Immune cells drive atherosclerotic lesion progression and plaque destabilization. Coronary heart disease patients undergoing noncardiac surgery are at risk for perioperative major adverse cardiac and cerebrovascular events (MACCE). It is unclear whether differential leukocyte subpopulations contribute to perioperative MACCE and thereby could aid identification of patients prone to perioperative cardiovascular events. First, we performed a hypothesis‐generating post hoc analysis of the LeukoCAPE‐1 study (n = 38). We analyzed preoperative counts of 6 leukocyte subpopulations in coronary heart disease patients for association with MACCE (composite of cardiac death, myocardial infarction, myocardial ischemia, myocardial injury after noncardiac surgery, thromboembolic stroke) within 30 d after surgery. Regulatory T cells (Tregs) were the only leukocyte subgroup associated with MACCE. We found reduced Tregs in patients experiencing MACCE versus no‐MACCE (0.02 [0.01; 0.03] vs. 0.04 [0.03; 0.05] Tregs nl−1, P = 0.002). Using Youden index, we derived the optimal threshold value for association with MACCE to be 0.027 Tregs nl−1. Subsequently, we recruited 233 coronary heart disease patients for the prospective, observational LeukoCAPE‐2 study and independently validated this Treg cutoff for prediction of MACCE within 30 d after noncardiac surgery. After multivariate logistic regression, Tregs < 0.027 cells nl−1 remained an independent predictor for MACCE (OR = 2.54 [1.22; 5.23], P = 0.012). Tregs improved risk discrimination of the revised cardiac risk index based on ΔAUC (area under the curve; ΔAUC = 0.09, P = 0.02), NRI (0.26), and IDI (0.06). Preoperative Treg levels below 0.027 cells nl−1 predicted perioperative MACCE and can be measured to increase accuracy of established preoperative cardiac risk stratification in coronary heart disease patients undergoing noncardiac surgery. [ABSTRACT FROM AUTHOR]

Introduction: Significant progress has been made in the targeted therapy of metastatic breast cancer (mBC) in recent years. In this context, new biomarkers enable personalized therapy management and individualized therapy monitoring. Therefore, the systemic treatment is based increasingly on the biological characteristics of the tumor disease. Given the challenges of obtaining fresh tumor tissue through biopsies, the significance of liquid biopsies for assessing circulating tumor cells (CTCs) or circulating tumor DNA is of growing importance for the detection of prognostic and predictive biomarkers. Multiple studies have shown that the number of CTCs decreases under therapy, especially under anti-HER2-targeted therapy, and that the expression of the HER2 status on CTCs could play a role in predicting therapy response and therapeutic monitoring. The aim of this study was to analyze the HER2 status of CTCs in mBC patients before and after 3 months of systemic therapy to evaluate changes in the number of HER2-positive CTCs. The study focuses on HER2-low, which plays an increasingly important role in clinical practice due to new developments of HER2 targeting antibody-drug conjugates. In this context, temporal and spatial heterogeneity of the disease represent a major diagnostic challenge. Methods: A total of 324 patients with complete immunohistochemistry of biopsied metastases were divided into five groups: HER2 negative (−)/hormone receptor (HR) negative (−), HER2 −/HR positive (+), HER2 +/HR±, HER2-low/HR+, and HER2-low/HR−. Before and after 3 months of a new therapeutic line for mBC, CTCs were enumerated and analyzed for HER2 expression using the CellSearch® system. Overall survival of all subgroups was calculated. Results: The analyses revealed a discrepancy between the HER2 status of CTCs and corresponding tumor tissues in 98 patients (30.2%). The number of CTCs in general and the number of HER2+ CTCs decreased during systemic treatment, mainly in HER2+ tumors, but also in the other subgroups. Conclusions: Discrepancy in the HER2 status of the metastases and of CTCs was observed in approximately one-third of patients. Measuring HER2 on CTCs could potentially offer a means to longitudinally monitor HER2 status during therapy and simultaneously address challenges such as tumor heterogeneity. Therefore, the predictive value of HER2 on CTCs should be further investigated in clinical trials. [ABSTRACT FROM AUTHOR]