Author:
Dalal Hina,Dahlgren Malin,Gladchuk Sergii,Brueffer Christian,Gruvberger-Saal Sofia K.,Saal Lao H.
Abstract
AbstractEstrogen receptor alpha (ERα, encoded by ESR1) is a well-characterized transcription factor expressed in more than 75% of breast tumors and is the key biomarker to direct endocrine therapies. On the other hand, much less is known about estrogen receptor beta (ERβ, encoded by ESR2) and its importance in cancer. Previous studies had some disagreement, however most reports suggested a more favorable prognosis for patients with high ESR2 expression. To add further clarity to ESR2 in breast cancer, we interrogated a large population-based cohort of primary breast tumors (n = 3207) from the SCAN-B study. RNA-seq shows ESR2 is expressed at low levels overall with a slight inverse correlation to ESR1 expression (Spearman R = −0.18, p = 2.2e−16), and highest ESR2 expression in the basal- and normal-like PAM50 subtypes. ESR2-high tumors had favorable overall survival (p = 0.006), particularly in subgroups receiving endocrine therapy (p = 0.03) and in triple-negative breast cancer (p = 0.01). These results were generally robust in multivariable analyses accounting for patient age, tumor size, node status, and grade. Gene modules consistent with immune response were associated to ESR2-high tumors. Taken together, our results indicate that ESR2 is generally expressed at low levels in breast cancer but associated with improved overall survival and may be related to immune response modulation.
Funder
H2020 Marie Skłodowska-Curie Actions
Cancerfonden
Vetenskapsrådet
Fru Berta Kamprads Stiftelse
ALF, Governmental Funding of Clinical Research within National Health Service
Medicinska Fakulteten, Lunds Universitet
Lund University
Publisher
Springer Science and Business Media LLC
Cited by
20 articles.
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