MedWire News: Plasma estradiol (E2) levels are associated with estrogen-responsive gene expression in estrogen receptor (ER)-positive breast cancers, study findings indicate.
Although such results may not appear surprising, previous findings have led to the view that intratumoral estrogen synthesis has a greater influence on estrogen signaling than uptake from the circulation, explain Anita Dunbier (Royal Marsden Hospital, London, UK) and colleagues.
“The data presented in this article challenge that view and strongly suggest that differences in plasma E2 levels between patients have a significant influence on breast tumors,” they add.
Dunbier and team obtained genome-wide RNA profiles from pretreatment core-cut tumor biopsies from 104 postmenopausal patients with primary ER-positive breast cancer treated with neoadjuvant anastrozole to identify genes for which expression was correlated with pretreatment plasma E2 levels.
They found that the expression of many known estrogen-responsive genes and gene sets was highly significantly associated with plasma E2 levels. These included trefoil factor 1 (TFF1), originally known as pS2, GREB1 (gene regulated by estrogen in breast cancer), PDZ domain-containing protein 1 (PDZK1), and the gene that encodes progesterone receptor (PGR).
Plasma E2 explained 27% of the average expression of these four estrogen-responsive genes, denoted AvERG by the researchers. The inclusion of ESR1 messenger RNA expression as a variable along with plasma E2 explained 37% of the variability in the AvERG.
Furthermore, exploratory analysis suggested that addition of the nuclear coregulators in a multivariable analysis with ER and E2 levels might additionally improve the relationship with the AvERG.
The researchers were able to validate their findings in an independent set of 73 ER-positive tumors. The also found that pretreatment plasma E2 significantly correlated with Ki67, a surrogate marker of clinical outcome, after 2 weeks of treatment.
“Plasma E2 levels are significantly associated with gene expression of ER-positive breast cancers and should be considered in future genomic studies of ER-positive breast cancer,” conclude Dunbier and co-authors in the Journal of Clinical Oncology.
They add: “As well as providing evidence for the importance of basal levels of E2 on breast cancer biology, the creation of AvERG provides a new index for understanding the clinical and biologic importance of other putative estrogenic influences.”
MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2010
Free abstract
