Background Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. The aim of this study was to explore the clinical evolution, stromal tumour-infiltrating lymphocytes (sTIL) infiltration and programmed death-ligand 1 (PD-L1) expression in a large IBC cohort. Patients and methods Data were collected prospectively from patients with IBC as part of an international collaborative effort since 1996. In total, 143 patients with IBC starting treatment between June 1996 and December 2016 were included. Clinicopathological variables were collected, and sTIL were scored by two pathologists on standard H&E stained sections. PD-L1 expression was assessed using a validated PD-L1 (SP142) assay. A validation cohort of 64 patients with IBC was used to test our findings. Results Survival outcomes of IBC remained poor with a 5-year overall survival (OS) of 45.6%. OS was significantly better in patients with primary non-metastatic disease who received taxane-containing (neo)adjuvant therapy ( P = 0.01), had a hormone receptor-positive tumour ( P = 0.001) and had lower cN stage at diagnosis ( P = 0.001). PD-L1 positivity on immune cells (42.9%) was higher in IBC than in non-IBC in both our patient samples and the validation cohort. Furthermore, PD-L1 expression predicted pCR ( P = 0.002) and correlated with sTIL infiltration ( P < 0.001). sTIL infiltration of more than 10% of the stroma was a significant predictor of improved OS (HR 0.47, 95% CI 0.27–0.81, P = 0.006) in a multivariate model. Conclusions IBC is characterised by poor survival and high PD-L1 immunoreactivity on sTIL. This suggests a role for PD1/PD-L1 inhibitors in the treatment of IBC. Furthermore, we showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC. Electronic supplementary material The online version of this article (10.1186/s13058-019-1108-1) contains supplementary material, which is available to authorized users.

Exercise training improves endothelial function in patients with chronic heart failure (CHF) through functional enhancement of circulating angiogenic cells and increased numbers of circulating endothelial progenitor cells (EPC). In contrast to healthy subjects, an immediate effect of acute exercise on CD34(+)/KDR(+) EPC is absent in CHF. Whether this reflects an attenuated or rather delayed mobilization, is addressed in the present study by measuring CD34(+)/KDR(+) EPC over a longer time period post-exercise. Seven CHF patients and eight healthy subjects (HS; 4 young and 4 age-matched subjects) underwent graded exercise testing (GXT). Venous blood was sampled before and 10, 30, and 60 min, 2, 4, 8, 12, 24 and 48 h following GXT to determine numbers of circulating CD34(+)/KDR(+) EPC (flow cytometry) and serum levels of stromal cell-derived factor (SDF)-1α (ELISA). In both HS groups, CD34(+)/KDR(+) EPC numbers increased within 10 min following GXT and remained elevated for up to 2 h. In CHF patients, the initial increase was small and normalized within 30 min. Evolution of CD34(+)/KDR(+) EPC numbers over time following GXT overall was attenuated in CHF versus HS (p = 0.036). Exercise considerably influenced SDF-1α levels over time (p = 0.0008), without a relation to the changes in CD34(+)/KDR(+) EPC. The immediate effect of acute exercise on CD34(+)/KDR(+) EPC numbers is not delayed, but significantly attenuated in CHF patients compared to HS.

Breast J. 2020;26:995-999. wileyonlinelibrary.com/journal/tbj | 995

Circulating tumor cells (CTCs) are viable tumor cells that are released into the circulatory system. CTCs have shown a prognostic value in numerous solid tumors. CTC research in epithelial ovarian carcinoma (EOC) has attracted only little attention. Since the primary route of metastasis in EOC is considered to be direct peritoneal spread in the abdominal cavity and distant metastases only occur in one third of the patients, it was thought that there is not enough shedding of tumor cells in the circulation. Nevertheless recent studies revealed an important role of hematogenous spread in EOC and showed that CTC status is associated with advanced tumor stage, CA-125 levels and residual disease after surgery. Furthermore the presence of CTCs correlates with shorter overall and disease free survival. However this prognostic value of CTCs in EOC seems to depend on the used isolation and detection methods. In EOC function- or density based enrichment methods seem to offer more promising results then epithelial cell adhesion molecule (EpCAM)-based approaches. This can be explained by a low number of EpCAM positive CTCs in EOC and the downregulation of EpCAM during epithelial-to-mesenchymal transition (EMT). The presence of CTCs might also have predictive value as CTC status was associated with treatment response in two studies and CTCs showed to be a better monitoring tool then CA-125 in a small population. The (genotypic) characterization of CTCs might become even more important in the future paving the way for CTCs to a true predictive "liquid tumor biopsy".