Infiltrating stromal immune cells in inflammatory breast cancer are associated with an improved outcome and increased PD-L1 expression

Abstract

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.

NOTCH and DNA repair pathways are more frequently targeted by genomic alterations in inflammatory than in non‐inflammatory breast cancers

“…As expected for breast cancers, the genomic profiles were heterogeneous in IBC. We found higher TMB in IBC compared to non‐IBC, possibly related to the higher genomic instability and complexity of the disease (Bekhouche et al , ), suggesting that immune checkpoint inhibitors warrant further investigation in IBC (Bertucci et al , ; Bertucci and Goncalves, ; Van Berckelaer et al , ; Van Laere et al , ). Such difference was independent from the molecular subtypes and the disease stage.…”

“…This observation confirms recent findings (Liang et al , ) of frequent alterations in BRCA1/BRCA2/POLE genes in IBC. It is likely that deficient DNA repair contributes to disease progression, as well as to the high TMB observed in IBC and indirectly to its peculiar immune microenvironment (Bertucci et al , ; Van Berckelaer et al , ; Van Laere et al , ). In addition, IBC showed more frequently a HRD and alterations in genes involved in mismatch repair, supporting the ongoing development of PARP inhibitors in IBC as radiosensitizers in phase I–II trials with veliparib (Jagsi et al , ) and olaparib (NCT03598257) (Michmerhuizen et al , ).…”

Plasma-Derived Reactive Species Shape a Differentiation Profile in Human Monocytes

“…In cancer, the infiltration of pro-inflammatory immune cells can be a major prognostic factor in patient survival [1,2]. Among others, macrophages are given an outstanding role in this process.…”

Implications for Online Management: Two Cases with COVID-19

“…Mentality is an important factor for overcoming a disease. Previous studies 3,4 have shown that negative emotions, such as anxiety and depression, can adversely affect the cellular immunity of cancer patients and, in turn, affect treatment efficacy. When a person is quarantined alone at home, it is inevitable that he/she may feel physically uncomfortable, scared, lonely, and depressed.…”