Email updates

Keep up to date with the latest news and content from Breast Cancer Research and BioMed Central.

Highly Accessed Editorial

A gene signature of loss of oestrogen receptor (ER) function and oxidative stress links ER-positive breast tumours with an absent progesterone receptor and a poor prognosis

Patrick Neven*, Toon Van Gorp and Karen Deraedt

Breast Cancer Research 2008, 10:109  doi:10.1186/bcr2135


See related research article by Yau and Benz, http://breast-cancer-research.com/content/10/4/R61

PubMed Commons is an experimental system of commenting on PubMed abstracts, introduced in October 2013. Comments are displayed on the abstract page, but during the initial closed pilot, only registered users can read or post comments. Any researcher who is listed as an author of an article indexed by PubMed is entitled to participate in the pilot. If you would like to participate and need an invitation, please email info@biomedcentral.com, giving the PubMed ID of an article on which you are an author. For more information, see the PubMed Commons FAQ.

Relationship of Ox-E/ER signature expression with clinical parameters and outcome in age-stratified cohorts

Christina Yau   (2008-09-22 14:49)  Buck Institute for Age Research email

In their recent editorial (Breast Cancer Res 2008, 10:109), Neven et al. highlight our recent finding (Breast Cancer Res 2008, 10:R61) that an experimentally derived oxidative stress gene expression signature, ‘Ox-E/ER’, identifies an aggressive subset of primary estrogen receptor (ER)-positive breast cancers associated with poor clinical outcome, and appears to outperform loss of progesterone receptor (PR) expression as a prognostic variable. Given their earlier studies suggesting an age-related association between PR status and HER2 overexpression in ER-positive breast cancers that could confound our oxidative stress analysis, they suggested that we further explore the prognostic relationship between our Ox-E/ER signature index and breast cancer PR status, stratifying for age-at-diagnosis. Returning to the public expression microarray datasets reported in our study, we were able to stratify most of the ER-positive breast cancers into either younger (<=age 45) or older (> age 45) age groups to correlate age group Ox-E/ER index values with array determined PR mRNA levels, ERBB2 overexpression (determined by mRNA content) and the average expression of the previously reported 71-gene proliferation signature. We also used the optimized Ox-E/ER index cutpoint to dichotomize available ER-positive age cohorts annotated for outcome -- either disease-specific survival (DSS; n = 201) or relapse-free survival (RFS; n = 263)-- in order to compare the prognostic value of the Ox-E/ER index with PR status. Within both age cohorts the Ox-E/ER index values showed significant positive correlations with the proliferation gene signature (younger: Pearson r = 0.32, p = 0.0009; older: r = 0.17, p = 0.0036) and ERBB2 status (younger: r = 0.29, p = 0.0028; older: r = 0.21, p = 0.0003), as well as a significant negative correlation with PR expression (younger: r = -0.25, p = 0.0097; older: r = -0.18, p = 0.0023). With regard to both DSS or RFS, the Ox-E/ER index cut-point (high vs. low status) appears to perform better as a prognostic marker for younger age-at-onset ER-positive breast cancers cases (DSS: younger: log-rank p= 0.005; older: log-rank p= 0.019; RFS: younger: log-rank p= 0.02; older: log rank p= 0.07). In comparison to PR status, while the Ox-E/ER index cut-point appears to perform better than PR status as a prognostic marker for the entire group (as published), this prognostic superiority may be restricted to the younger age cohort (DSS: log-rank p=0.005 for Ox-E/ER vs. 0.25 for PR status; RFS: log-rank p=0.02 for Ox-E/ER vs. 0.60 for PR status) , since we fail to see significant differences in their respective abilities to determine the outcome of older ER-positive cases. An important caveat to note is the small number of PR-negative cases in the younger cohort; additional studies utilizing age cohorts better balanced for PR status are warranted to confirm this finding.

Comment by Christina Yau and Christopher C Benz

Competing interests

C. Yau and CC Benz are the authors of the article featured in the editorial. This comment contains results from additional analysis performed in response to a question raised therein.

top

Post a comment