ER+ breast tumors may involve ER-independent mechanisms of gene activation

It keeps getting more complex!

It helps explain why targeted drugs are only likely to be partially successful.

I found this a while ago but did not appreciate its significance.

In terms of seeking solutions it underlines the need for a broad approach including diet.

My admiration and a happy and healthy new year to all


RB




http://www.ncbi.nlm.nih.gov/entrez/q...15&query_hl=10


1: Hum Mol Genet. 2003 Dec 15;12(24):3245-58. Epub 2003 Oct 21. Related Articles, Links


Classifying the estrogen receptor status of breast cancers by expression profiles reveals a poor prognosis subpopulation exhibiting high expression of the ERBB2 receptor.

Kun Y, How LC, Hoon TP, Bajic VB, Lam TS, Aggarwal A, Sze HG, Bok WS, Yin WC, Tan P.

National Cancer Centre, Singapore, Republic of Singapore.

Recent work using expression profiling to computationally predict the estrogen receptor (ER) status of breast tumors has revealed that certain tumors are characterized by a high prediction uncertainty ('low-confidence'). We analyzed these 'low-confidence' tumors and determined that their 'uncertain' prediction status arises as a result of widespread perturbations in multiple genes whose expression is important for ER subtype discrimination. Patients with 'low-confidence' ER+ tumors exhibited a significantly worse overall survival (P=0.03) and shorter time to distant metastasis (P=0.004) compared with their 'high-confidence' ER+ counterparts, indicating that the 'high-' and 'low-confidence' binary distinction is clinically meaningful. We then discovered that elevated expression of the ERBB2 receptor is significantly correlated with a breast tumor exhibiting a 'low-confidence' prediction, and this association was subsequently validated across multiple independently derived breast cancer expression datasets employing a variety of different array technologies and patient populations. Although ERBB2 signaling has been proposed to inhibit the transcriptional activity of ER, a large proportion of the perturbed genes in the 'low-confidence'/ERBB2+ samples are not known to be estrogen responsive, and a recently described bioinformatic algorithm (DEREF) was used to demonstrate the absence of potential estrogen-response elements (EREs) in their promoters. We propose that a significant portion of ERBB2's effects on ER+ breast tumors may involve ER-independent mechanisms of gene activation, which may contribute to the clinically aggressive behavior of the 'low-confidence' breast tumor subtype.

PMID: 14570715 [PubMed - indexed for MEDLINE]

[karenann]

Does this mean if you are highly er+ you have a better prognosis than someone who has lower er+ status?

[CherylS]

Good question Karenann. What in the world does this mean? Some of these articles, although I am sure very relevant mean nothing to most of us because they are in a language we cannot understand. How much do we really want to add to our confusion? I prefer to add to my understanding and knowledge, so if someone can interpret this, thank you.

Here is the link to the full article which may help. The little box did not copy across.

I too do not understand much of it. The article recognises gaps in knowledge. It does undeline the complexity of it all.

Is it not raising the possibility of a grey area between ER+ and ER-, and even "crosstalk" between the two? Would that not have treatment and diagnostic implications. Might it not go someway to putting some shred of explanation where there are diagnostic difficulties between ER+ and ER-

I take your point about adding to knowledge. It was either post it as it was or not post it as I do not have sufficeint knowledge to "translate" it.

If somebody can translate this into simple terms with certainty please help.

http://hmg.oxfordjournals.org/cgi/co...ull/12/24/3245

My first reaction is HUH??
My second is I'm er- and what I decipher scares me.
And 3rd, I plan to make a copy and let my onc. read it.
Carol

And-- does this mean that you're more likely to be er- if you are her2 positive?
Carol
I'm confused

[karenann]

I'll tell you what...just when I think I am understanding what this report is saying, I get confussed all over again. When they use the term, low confidence and high confidence, are they referring to a person who is, er+ 45% (low confidence) and er+95% (high confidence)?

I think I'll have my husband take a look and see what he has to say.

Karen