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Supplemental Table S3 from An Endothelial Gene Signature Score Predicts Poor Outcome in Patients with Endocrine-Treated, Low Genomic Grade Breast Tumors

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journal contribution
posted on 2023-03-31, 18:52 authored by Nicholas P. Tobin, Kristian Wennmalm, Linda S. Lindström, Theodoros Foukakis, Liqun He, Guillem Genové, Arne Östman, Göran Landberg, Christer Betsholtz, Jonas Bergh

Multivariable analysis of prognostic markers in endocrine-treated patients

Funding

Swedish Cancer Society

Stockholm Cancer Society

BRECT

King Gustav V jubilee fund

ALF

Linné Foundation

Swedish Research Council

Swedish Research Council for Health, Working Life and Welfare

the Märit & Hans Rausing Foundation

Knut and Alice Wallenberg Foundation

AstraZeneca

History

ARTICLE ABSTRACT

Purpose: The ability of vascular genes to provide treatment predictive information in breast cancer patients remains unclear. As such, we assessed the expression of genes representative of normal endothelial microvasculature (MV) in relation to treatment-specific patient subgroups.Experimental Design: We used expression data from 993 breast tumors to assess 57 MV genes (summarized to yield an MV score) as well as the genomic grade index (GGI) and PAM50 signatures. MV score was compared with CD31 staining by correlation and gene ontology (GO) analysis, along with clinicopathologic characteristics and PAM50 subtypes. Uni-, multivariate, and/or t-test analyses were performed in all and treatment-specific subgroups, along with a clinical trial cohort of patients with metastatic breast cancer, seven of whom received antiangiogenic therapy.Results: MV score did not correlate with microvessel density (correlation = 0.096), but displayed enrichment for angiogenic GO terms, and was lower in Luminal B tumors. In endocrine-treated patients, a high MV score was associated with decreased risk of metastasis [HR 0.58; 95% confidence interval (CI), 0.38–0.89], even after adjusting for histologic grade, but not GGI or PAM50. Subgroup analysis showed the prognostic strength of the MV score resided in low genomic grade tumors and MV score was significantly increased in metastatic breast tumors after treatment with sunitinib + docetaxel (P = 0.031).Conclusions: MV score identifies two groups of better and worse survival in low-risk endocrine-treated breast cancer patients. We also show normalization of tumor vasculature on a transcriptional level in response to an angiogenic inhibitor in human breast cancer samples. Clin Cancer Res; 22(10); 2417–26. ©2016 AACR.