Abstract
BackgroundInflammatory 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 methodsData 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.ResultsSurvival 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.ConclusionsIBC 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.
Highlights
Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer
IBC is characterised by poor survival and high programmed death-ligand 1 (PD-L1) immunoreactivity on stromal tumour-infiltrating lymphocytes (sTIL)
We showed that PD-L1 expression predicts response to neo-adjuvant therapy and that sTIL have prognostic significance in IBC
Summary
Inflammatory breast cancer (IBC) is a rare and rapidly progressive form of invasive breast cancer. Hormonal or targeted therapy against HER2 is offered if indicated Notwithstanding this aggressive treatment, the overall survival (OS) remains lower than in non-inflammatory breast cancer (nIBC) [5]. Further research is warranted to unravel the molecular biology of IBC In this context, the World IBC Consortium (WIBCC) reported a 79-gene signature that discriminates between IBC and nIBC patient samples, indicating a distinct molecular basis for IBC [6]. The World IBC Consortium (WIBCC) reported a 79-gene signature that discriminates between IBC and nIBC patient samples, indicating a distinct molecular basis for IBC [6] Translating this gene signature into molecular concepts suggested that the biology of IBC is characterised by an altered TGF-β pathway and immune response program. Since IBC is characterised by an increased mutational load, this might lead to increased tumour antigen-based attraction of cytotoxic T cells [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
