Different associations of estrogen receptor β isoforms, ERβ1 and ERβ2, expression levels with tumor size and survival in early- and late-onset breast cancer

Background: In breast cancer, little is known about the consequences of co-expression of ER alpha with the second estrogen receptor, ER beta, and its isoforms in light of their joint prognostic value. Previously reported correlations have been based mostly on independent ER alpha and ER beta expression levels in breast tumors. Purpose: To address whether the expression ratio of ER alpha and ER beta and its isoforms may be a more important parameter than their absolute levels, we analyzed relative mRNA expression ratios of ER beta 1 to ER beta 2 and ER alpha in 74 clinical samples of invasive breast cancer including 39 early-onset and 35 late-onset breast cancers. Expression levels were correlated with clinical and histopathological parameters and disease-free interval. Results: A specific correlation of ER beta 1 expression levels with tumor size was detected in early-onset breast cancer patients and of ER beta 2 levels with tumor size in late-onset patients. Expression of both ER beta isoforms inversely correlated with expression of the two estrogen regulated genes, progesterone receptor and pS2 in both groups. Higher levels of ER beta 2 than ER beta 1 isoform were associated with a better outcome in late-onset patients. Conclusions: Our results suggest that different isoforms of ER beta may be involved in suppression of tumor growth in young and elder patients and may have different prognostic values. (C) 2012 Elsevier Ireland Ltd. All rights reserved.