Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study

Schettini, Francesco; Sobhani, Navid; Ianza, Anna; Triulzi, Tiziana; Molteni, Alfredo; Lazzari, Maria Chiara; Strina, Carla; Milani, Manuela; Corona, Silvia Paola; Sirico, Marianna; Bernocchi, Ottavia; Giudici, Fabiola; Cappelletti, M.; Ciruelos, Eva; Jérusalem, Guy; Loi, S.; Fox, Stephen B.; Generali, Daniele

doi:10.1007/s10549-020-05856-3

Cited by 13 publications

(14 citation statements)

References 43 publications

(62 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…2 e). In addition, genes related to angiogenesis have been reported to play essential roles in modulating the tumour microenvironment and the immune environment [ 36 ]. We calculated each sample's angiogenesis score and found that scores for the four groups were significantly different.…”

Section: Resultsmentioning

confidence: 99%

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

et al. 2021

View full text Add to dashboard Cite

Background Hepatocellular carcinoma (HCC) has a poor prognosis and has become the sixth most common malignancy worldwide due to its high incidence. Advanced approaches to therapy, including immunotherapeutic strategies, have played crucial roles in decreasing recurrence rates and improving clinical outcomes. The HCC microenvironment is important for both tumour carcinogenesis and immunogenicity, but a classification system based on immune signatures has not yet been comprehensively described. Methods HCC datasets from The Cancer Genome Atlas (TCGA), the Gene Expression Omnibus (GEO), and the International Cancer Genome Consortium (ICGC) were used in this study. Gene set enrichment analysis (GSEA) and the ConsensusClusterPlus algorithm were used for clustering assessments. We scored immune cell infiltration and used linear discriminant analysis (LDA) to improve HCC classification accuracy. Pearson's correlation analyses were performed to assess relationships between immune signature indices and immunotherapies. In addition, weighted gene co-expression network analysis (WGCNA) was applied to identify candidate modules closely associated with immune signature indices. Results Based on 152 immune signatures from HCC samples, we identified four distinct immune subtypes (IS1, IS2, IS3, and IS4). Subtypes IS1 and IS4 had more favourable prognoses than subtypes IS2 and IS3. These four subtypes also had different immune system characteristics. The IS1 subtype had the highest scores for IFNγ, cytolysis, angiogenesis, and immune cell infiltration among all subtypes. We also identified 11 potential genes, namely, TSPAN15, TSPO, METTL9, CD276, TP53I11, SPINT1, TSPO, TRABD2B, WARS2, C9ORF116, and LBH, that may represent potential immunological biomarkers for HCC. Furthermore, real-time PCR revealed that SPINT1, CD276, TSPO, TSPAN15, METTL9, and WARS2 expression was increased in HCC cells. Conclusions The present gene-based immune signature classification and indexing may provide novel perspectives for both HCC immunotherapy management and prognosis prediction.

show abstract

Section: Resultsmentioning

confidence: 99%

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Lymphocytes, whether in peripheral blood or as tumor-in ltrating lymphocytes, play a major role in controlling disease progression. For example, in patients receiving everolimus for mBC, Schettini et al reported that responders had a higher number of circulating CD8+ and CD4+ T cells, and increased pretreatment in ltration of these cells in the tumor microenvironment than non-responders [30].…”

Section: Discussionmentioning

confidence: 99%

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors

Rottier

SILVA

Johnson

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Cyclin dependent kinase inhibitors (CdK4/6i) changed the course of hormone receptor positive (HR+) HER2negative (HER2-) metastatic breast cancer (mBC). To date, no factors have been shown to predict response to CdK4/6i. Neutrophil-to-lymphocyte ratio (NLR), an indicator of the host systemic inflammatory response, is an independent prognostic factor for survival in cancers. We conducted this study to evaluate the addition of NLR for survival assessment in mBC patients treated with first line CdK4/6i. Methods: All mBC patients treated with first line CdK4/6i between November 2015 and December 2019 were retrospectively included. We analyzed 12-month progression free survival (PFS), overall survival (OS) and response rate according to NLR in univariable and multivariable analysis.Results: A total of 126 patients treated with palbociclib (n=101), ribociclib (n=18) or abemaciclib (n=7) were included, with a median follow-up of 16 months [range: 2.9-37]. Median age was 65 years [29-86], 88% patients had good performance status (0-1). Most patients were included at the metastatic relapse stage (71%) and 20% had visceral metastases without bone lesions. High NLR (≥ 2.53) was significantly associated with worse PFS (Hazard Ratio (HR)=0.52, CI95% =[0.29-0.94]). Fourteen patients died (11.1%). Complete responses were more frequent in the low NLR group (<2.53) (14.5% vs. 3.1%, p=0.029). Conclusion: High NLR is associated with worse PFS in HR+ HER2- mBC patients treated with first line CdK4/6i. NLR is a reliable and inexpensive prognostic marker, easily accessible in routine clinical practice, which could optimize the therapeutic strategy. These results need to be confirmed in larger prospective studies.

show abstract

“…62,63 Patients with a neutrophil to lymphocyte ratio below 4.4 had a superior PFS compared with patients with baseline neutrophil to lymphocyte ratio above 4.4 (Log Rank test p = 0.01). 62 Changes in Standardized Uptake Values (SUV) of Positron Emission Tomography (PET) scans at 3 months compared with baseline SUV were examined in a small study of 31 patients with metastatic ER positive, HER2 negative breast cancer receiving exemestane and everolimus. 64 A change of SUV by more than 28.8% was found to be an optimal cut-off to predict PFS at 10 months.…”

Section: Clinical Biomarkersmentioning

confidence: 96%

“…62 Data from a sub-set of patients from the phase IIIb trial mentioned in the previous paragraph disclosed that the neutrophil to lymphocyte ratio in peripheral blood was predictive of outcomes to treatment with exemestane and everolimus. 62,63 Patients with a neutrophil to lymphocyte ratio below 4.4 had a superior PFS compared with patients with baseline neutrophil to lymphocyte ratio above 4.4 (Log Rank test p = 0.01). 62 Changes in Standardized Uptake Values (SUV) of Positron Emission Tomography (PET) scans at 3 months compared with baseline SUV were examined in a small study of 31 patients with metastatic ER positive, HER2 negative breast cancer receiving exemestane and everolimus.…”

Section: Clinical Biomarkersmentioning

confidence: 99%

Biomarkers of everolimus efficacy in breast cancer therapy

Voutsadakis

2022

J Oncol Pharm Pract

View full text Add to dashboard Cite

Objective Everolimus is an inhibitor of serine/ threonine kinase mTOR. The drug is approved for the treatment of metastatic ER positive, HER2 negative breast cancers and benefits a subset of patients with these breast cancers in combination with hormonal therapies. Despite extensive efforts, no additional predictive biomarkers to guide therapeutic decisions for everolimus have been introduced in clinical practice. Data sources This paper discusses predictive biomarkers for everolimus efficacy in breast cancer. A search of the medline and web of science databases was performed using the words “everolimus” and “biomarkers”. References of retrieved articles were manually scanned for additional relevant articles. Data Summary Everolimus benefits a subset of patients with metastatic ER positive, HER2 negative breast cancers in combination with hormonal therapies. Despite extensive efforts no additional predictive biomarkers to guide therapeutic decisions for everolimus therapy have been confirmed for use in clinical practice. However, promising biomarker leads for everolimus efficacy in breast cancer have been suggested and include expression of proteins in the mTOR pathway in ER positive, HER2 negative breast cancers. In HER2 positive cancers PIK3CA mutations, and PTEN expression loss are prognostic. Other clinical predictive biomarkers with more limited data include characteristics derived from whole genome sequencing, subsets of circulating leukocytes and changes in Standardized Uptake Values (SUV) of Positron Emission Tomography (PET) scans. Conclusions Putative predictive biomarkers for everolimus efficacy in breast cancer patients, both genomic and clinical, deserve further study and could lead to a better selection of responsive patients.

show abstract

Immune system and angiogenesis-related potential surrogate biomarkers of response to everolimus-based treatment in hormone receptor-positive breast cancer: an exploratory study

Cited by 13 publications

References 43 publications

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

Immune signature-based hepatocellular carcinoma subtypes may provide novel insights into therapy and prognosis predictions

Pretreatment neutrophil to lymphocyte ratio as prognostic factor in metastatic breast cancer treated with cyclin dependent kinase 4/6 inhibitors

Biomarkers of everolimus efficacy in breast cancer therapy

Contact Info

Product

Resources

About