An Endothelial Gene Signature Score Predicts Poor Outcome in Patients with Endocrine-Treated, Low Genomic Grade Breast Tumors
2016 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 22, no 10, 2417-2426 p.Article in journal (Refereed) PublishedText
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.
Place, publisher, year, edition, pages
2016. Vol. 22, no 10, 2417-2426 p.
Cancer and Oncology
IdentifiersURN: urn:nbn:se:uu:diva-297782DOI: 10.1158/1078-0432.CCR-15-1691ISI: 000375839200014PubMedID: 26769751OAI: oai:DiVA.org:uu-297782DiVA: diva2:943625
FunderSwedish Cancer SocietySwedish Research Council, 524-2014-4483Swedish Research Council, 521-2014-2057Forte, Swedish Research Council for Health, Working Life and Welfare, 2014-1962Knut and Alice Wallenberg FoundationAstraZeneca